USE OF PALLIATIVE SURGERY IN THE TREATMENT OF CANCER PATIENTS

The Norwegian Center for Medical Technology Assessment (SMM) Report no. 8/2003

Medical method assessment based on a review of the literature conducted by a group of experts

Preface

Palliative surgical treatment of cancer patients is considered in Norwegian Official Re-port no. 1997:20, Care and Knowledge: the Norwegian Cancer Plan. Among other is-sues, this report focuses on various treatment principles for cancer and includes a spe-cial section on palliative cancer surgery which underscores the need for more know-ledge about its symptom-preventing potential and calls for a clarification of the indica-tions for palliative surgical intervention.

The Norwegian Center for Medical Technology Assessment (SMM) was asked by the Ministry of Health and Social Affairs to conduct a review of the literature on the use and effect of palliative surgery in cancer patients. The study was conducted as an as-sessment of medical methods, i.e. a systematic retrieval and critical assessment ac-cording to predetermined criteria of all published and available scientific documenta-tion.

To a greater extent, the SMM wants to include the views of patients and users. For this method assessment we invited the Norwegian Cancer Society to act as a representative of the users; their comments are included in chapter 5.3 on the ethical aspects of the use palliative surgery for cancer patients. An appendix presents their views in greater detail.

The group of experts was constituted in a meeting on 3 March 2000 and has had these members:

Chair: Professor Karl-Erik Giercksky, The Norwegian Radium Hospital, Oslo Professor Jon Erik Grønbech, St. Olav University Hospital, TrondheimAss. chair of department Tor Hammelbo, Vest-Agder Hospital, KristiansandSenior physician Henry Hirschberg, Rikshospitalet University Hospital, OsloProfessor Tryggve Lundar, Rikshospitalet University Hospital, OsloSenior physician Odd Mjåland, Vestfold Hospital, TønsbergSenior physician Lodve Stangeland, Haukeland University Hospital, BergenProfessor Jon Arne Søreide, Rogaland Central Hospital, StavangerSenior physician Clement Trovik, Haukeland University Hospital, BergenChair of section Anders Walløe, Ullevaal University Hospital, OsloChair of department Rolf Wahlqvist, Aker University Hospital, Oslo Clinic of UrologySenior physician Nicolai Wessel, Aker University Hospital, Oslo Clinic of UrologyProject coordinators: research officer Krystyna Hviding and senior research officer Lise Lund Håheim of the Norwegian Center for Medical Technology Assessment

The following were involved in an early phase of the project:Senior physician Håkon Wæhre, Innlandet Hospital, Lillehammer Chair of department Paal-Henning Pedersen, Haukeland University Hospital

Data on palliative surgery in Norwegian hospitals were compiled by senior adviser Øyvind Christensen and data specialist Daniel Nguyen, both of the Norwegian Patient

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Registry, SINTEF Unimed, and senior adviser Leena Kiviluoto, Patient Funding and Classification Unit, SINTEF Unimed.

The section of health economics is written by professor Ivar Sønbø Kristiansen and the chapter on ethical aspects by associate professor Bjørn Hofmann, both of the SMM. Contributing views from the Norwegian Cancer Society were presented by in-formation officers Anne-Liv Hval and Anne Grasdal.

All members of the group of experts have declared that they have no competing in-terests or commercial or other interests related to the project that would prevent them from contributing to an assessment of the literature that is as objective a possible. The report has been approved by the SSM’s steering committee. The translation into Eng-lish is done by Sveinung Løkke.

Berit Mørland Lise Lund HåheimDirector Senior research officer

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Contents

1 Comments by the SMM...........................................................................62 Introduction............................................................................................10

2.1 Background.......................................................................................102.2 The group’s terms of reference.........................................................11

3 Method 143.1 Mode of work.....................................................................................143.2 Literature search...............................................................................143.3 Assessment of the literature..............................................................16

4 Results 194.1 Gastroenterologic surgery.................................................................19

4.1.1 Dysphagia caused by oesophageal cancer.........................194.1.2 Icterus..................................................................................244.1.3 Retention in pancreatic cancer............................................264.1.4 Retention and/or bleeding in cases of gastric cancer..........274.1.5 Intestinal obstruction............................................................284.1.6 Intestinal bleedings..............................................................314.1.7 Pain • quality of life • prolongation of life..............................32

4.2 Neurosurgery....................................................................................354.2.1 Quality of life, neurologic deficiency /svikt/QQQ and survival in primary cancer of the brain............................................................354.2.2 Neurologic deterioration and survival in brain metastasis. . .374.2.3 Neurologic deterioration in cases of metastasis to the spine

384.3 Orthopaedic surgery..........................................................................40

4.3.1 Surgical treatment of bone metastases...............................404.3.2 Pain or fracture caused by metastases to the humerus......434.3.3 Pain or fracture caused by metastases to the femur...........434.3.4 Pain or fracture caused by metastases to the pelvis...........454.3.5 Pain or fracture caused by metastases to the spine............46

4.4 Thoracic surgery...............................................................................484.4.1 Difficulty breathing and survival in metastasis to the lungs..484.4.2 Obstruction of the central airways.......................................494.4.3 Stenosis/occlusion of the superior vena cava......................50

4.5 Urologic surgery................................................................................514.5.1 Haematuria..........................................................................534.5.2 Urinary retention..................................................................554.5.3 Flank pain............................................................................574.5.4 Metabolic disturbances from renal cancer...........................574.5.5 Vesicovaginal/intestinal fistula.............................................584.5.6 Malignant ureter obstruction................................................58

5 Relevant assessment criteria...............................................................615.1 Economic aspects of palliative cancer surgery.................................61

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5.2 Palliative cancer surgery in Norwegian hospitals..............................625.3 Ethical aspects of palliative surgery for cancer patients....................64

5.3.1 The duty to help...................................................................655.3.2 Compassion and vulnerability..............................................655.3.3 Risk and lack of knowledge.................................................655.3.4 The wish to do ”everything that is possible”.........................665.3.5 Patient autonomy and information.......................................675.3.6 Priorities...............................................................................68

Pursuant to Norwegian Official Reports no. 18, 1997, the health services shall set priorities according to 1) severity, 2) benefits, and 3) cost effi-ciency. This is specified in the Patients’ Rights Act (334), from which it appears that the patient has a right to necessary help if: 1) the patient either to some extent has a worse prognosis in terms of remaining lifespan if help is delayed, and 2) the patient may have an expected be-nefit of the help, and 3) expected costs are in a reasonable relationship to the effect of the treatment. Incurable cancer meets the requirement of severity. For most form of palliative surgery, the benefit is either poor or undocumented. This does not necessarily imply that there is no benefit, but that the requirement of documented benefit, b), is not filled. If the be-nefit is not known, nothing can be said about cost efficiency; c) the costs of palliative surgery are considerable (roughly estimated at 50% of the resources in cancer surgery, cf. chapter 2.1). Solely on the basis of priority criteria, palliative surgery will not be given priority.....................68

5.3.7 Research and ethics............................................................695.3.8 Knowledge and ethics.........................................................69

6 Discussion 71

12 Appendixes12.1 Search strategies12.2 Codes for relevant hospitalisations

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1 Comments by the SMM

BackgroundAs a follow-up of the Norwegian Cancer Plan, the Norwegian Center for Medical Technology Assessment (SMM) was commissioned by the Ministry of Health and So-cial Affairs with conducting a review of the literature on the use and effects of palliat-ive cancer surgery and palliative procedures in the domain of surgery and examine the Norwegian practice in this field.

Palliative cancer surgery is an important element in the field of palliation for cancer patients. It is considered in Norwegian Official Report no. 1997:20, Care and Know-ledge: the Norwegian Cancer Plan, which has a special section devoted to palliative cancer surgery, underscoring the importance of a better knowledge basis on the effect of this treatment: “Charting the effects of palliative symptom-preventing surgery should be given priority as an important issue in the care for cancer patients in Nor-way.” Furthermore, reference is made to a committee set up under the Ministry of Health and Social Affairs to investigate “Surgical intervention and treatment in palli-ative cancer therapy” from 1996 which points out the need for registration of treat-ments carried out: “It is important to establish systems that over time could increase our knowledge about the impact of palliative surgery that could benefit Norwegian patients.”

The purpose of palliative cancer surgery is the relief of symptoms and the prolonga-tion of life, not cure. Patients who need such treatment have advanced cancer; the treatment is directed towards the primary tumour, recidivation, metastases, or local and regional problems. The methods are many and the surgery can be extensive. The documentation of the treatment is of varying quality and partly deficient for several procedures that are carried out, in spite of the great extent of and need for palliative cancer surgery.

Method and approachThe terms of reference called for a critical review based on systematically identified literature. It was a considerable task; the work was devided among the five most rel-evant surgical subspecialties: gastroenterologic surgery, neurosurgery, and ortho-paedic, thoracic and urologic surgery. Problems arising from gynaecologic cancer are mostly covered by gastroenterologists and urologists.

After a review of 3731 abstracts, 166 studies have been used, with an emphasis on pa-tient series and a relatively few randomised controlled studies. The evidence level in the literature selected varied between the fields.

ResultsPalliation of symptomsThe group of experts has focused on surgical treatment of symptoms that hinder nor-mal bodily functions as well as other unacceptable torments. A wide variety of treat-

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ment modalities have been used; some have been superceded new methods and are no longer in use. Some main results of the review of the literature:

Surgical palliation of symptoms includes various way of relieving obstruction in the alimentary tract: in the oesophagus, the stomach, the intestines, or the cystic tract. The modalities are mainly bypass surgery, stenting or laser therapy. Stenting is increas-ingly used in the treatment of icterus or pruritus due to a stenosis in the cystic tract. Laser therapy can be used for obstruction or bleeding in the oesophagus and in the lower part of the colon and rectum.

Laser provides immediate relief of symptoms from obstruction in the central airways and may be combined with other therapies such as stenting and brachytherapy. Stent-ing has an immediate effect on obstructions in the superior vena cava to the heart.

There are many modes of treatment of symptoms that arise from cancer in the urinary bladder, prostate and kidneys. Blood in the urine due to prostate cancer or cancer of the bladder is treated with a well established surgical method. Rinsing of the bladder with a styptic solution is reasonably well documented.

Treatment of bleeding and also flank pain in cases of stenosis of the renal artery is re-liably documented and has generally speaking superceded conventional surgery. Stenting can also be used in urinary retention in prostate cancer.

Pinching off of the ureter because of pressure or ingrowth of cancer tissue is now treated with ostomy of the ureter or stenting of the ureter. These methods applied for palliative purposes show documented benefit and have, in fact, replaced major urine diverting operations.

Pain is the major symptom in bone metastases; if radiotherapy does not have the de-sired effect, surgery may be an option. Treatment of fractures must be done with /avstivning/ QQQ so that the patient regains function as soon as possible, independ-ently of the degree of healing.

Surgery for metastasis to the brain is beneficial for those with metastasis and an other-wise stable cancer condition. When metastasis to the spine leads to threatening palsies, treatment has to be carried out as soon as possible in order to have effect.

Prolongation of liveSome procedures have been assessed in terms of prolongation of life. There are indic-ations to the effect that gastrectomy in incurable gastric cancer gives longer survival. Resection of a pulmonary metastasis may increase remaining lifespan. Laser has the advantage of saving lung tissue and it improves the chances of resecting metastases that are difficult to access. Resecting the tumour instead of biopsy in glioma multi-forme gives longer survival; so does resecting the metastasis in addition to radio-therapy.

Palliative proceduresOur review shows that elective palliative procedures, on the basis of documented ef-fect, may be subdivided into four main groups:

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– A small number of procedures that in controlled clinical trials or large series of patients have been shown to have a reliable and measurable effect compared to other procedures. Examples included the use of laser or stenting for obstructions of the oesophagus, or surgical bypass or stenting for obstructions in the biliary ducts.

– Routinely used and often relative simple procedures, often with a high degree of at least temporary effect, that represent a therapeutic tradition introduced before con-trolled clinical trials became the standard. Transurethral resection for bleeding and urinary retention in cancer of the bladder and the prostate are typical examples of this type of palliative treatment. There is clearly a danger of this tradition being carried over into major procedures without palliative effect; this is illustrated by the fact that resection of a spinal disk without /avstivning QQQ is now considered to be without effect.

– The general rule is that it is difficult to document the effectiveness of symptom-free, life-extending palliative surgery (not directed towards symptoms). Still it seems clear that when optimal preoperative and perioperative staging is done, pa-tients who may profit from such procedures may be identified. Examples of this are seen in the fields of neurosurgery and gastropancreatic surgery.

– The majority of the most common palliative procedures have a described effect, though there is not sufficiently scientific documentation as they are based on se-lected patient materials and retrospective comparisons. As the nature of the prob-lems (ileus, difficulty breathing, dysphagia etc.) rarely allows untreated controls, the comparison will often be between procedures that clinically would be comple-mentary (laser and stenting, blocking and tubing).

Relevant assessment criteriaFor administrative purposes, Norway’s health services are organised in five regions. Data on registered hospitalisations in these regions have been used to throw some light on the extent of palliative cancer surgery and the resources it requires. There is no special registration of whether the surgery had a palliative or curative intention. During the 1999–2002 period, there was no overall increase in cancer surgery as a percentage (8.3%) of all surgery. The five regions had varying proportions of cancer surgery relative to all surgery, and variations by year. As regards surgical treatment of metastases, there are few such procedures in urologic surgery, but many in cancers in the alimentary tract.

Specific analyses of health economics aspects have not been carried out, though the economic aspects of palliative cancer surgery are discussed in this report. Few studies have been carried out that are suited to estimate the cost-benefit of palliative cancer surgery; hence it is difficult to give a total assessment.

Ethical issues are considered with a focus on the role of the physician, the needs of the patient, research ethics and research needs in relation to developing a basis for setting priorities. Research in this area is morally and methodically challenging. However, the paucity of high-level studies makes the knowledge basis weaker than what is called for. Palliative surgery is a potentially valuable treatment, but for patients with a short remaining lifespan, surgical treatment will not always be the best alternative for relieving symptoms. Palliative surgery requires assessments with a moral basis as well as surgical skills.

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Comments

This systematic review of the literature shows that there are varying levels of evidence for many procedures in these fields. This reflects complex clinical situations in which to carry out randomised studies.

The group of experts has made a comprehensive effort and concludes that the sci-entific evidence presented in the available literature is inconclusive. In several areas there is a need for additional documentation. Still, in the opinion of the group of ex-perts this review of the literature gives Norwegian cancer care a platform that could provide direction in relation to what should be the priorities in future research within this field.

As palliative cancer surgery consumes a very considerable share of the resources spent on the surgical care for cancer patients, all procedures should be registered as palliative or curative when they are coded. Compared with data from the Norwegian Cancer Registry, this would provide a new dimension for measuring the effect as well as the costs of surgical cancer care.

The present report could provide a better foundation for advice to the individual pa-tient on whether or not the relevant treatment is of benefit to him or her in terms of improved functioning, relief of pain and other symptoms, and a better quality of life, seen in relation to the patient’s reserve of treatment options and excepted remaining lifespan. The report describes a large number of surgical treatments that to some ex-tent are quite extensive. Patients will be in need of information on expected improve-ment after surgery and the disadvantages surgery may bring so that they may make a choice on whether to go through palliative cancer surgery. The lack of documentation of effect calls on the surgeon to exercise judgment in the choice of treatment in order to contribute to the treatment being a benefit for the patient.

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2 Introduction

2.1BackgroundSymptoms from a tumour usually occur when the organ in question is no longer able to perform its normal function or when the growing tumour for mechanical reasons causes pain or reduced functioning in adjacent organs. Metastases from the primary tumour add a new dimension to the clinical picture because the daughter tumours are often localised in other organ systems and, hence, lead to the development of other symptoms that are hard to predict. In some more rare cases, tumours make reactive products that, brought with the bloodstream, inflict functional disturbances on other organ systems.

In a relatively near future, according to the Norwegian Cancer Registry, every third person in Norway will develop a malignant disease in the course of their lifetime. Al-most half of them will develop spreads QQQ or have a local recidivation of the dis-ease; sooner or later they will be evaluated for palliative treatment. If one also takes into account the fact that a large number of primary cancer operations only have a local palliative effect and not the desired curative effect, it is evident that more than half of the surgical resources within cancer treatment are used either for purely palliat-ive procedures or for procedures on the borderline between palliation and cure, primarily because of the fact that one still does not have exact knowledge about the real extent of the disease at the time of treatment.

Palliative surgery is one of several therapeutic modalities that are not intended to cure the patient’s cancer, but are carried out with an intention to prolong life, relieve symp-toms, or prevent symptoms. One has chosen to define as necessary emergency surgery acute palliative surgery which is intended to relieve acutely occurring and severe pain or haemorrhage that cannot be relieved with optimised non-surgical or medical treat-ment. These issues have not been included in the selection of literature that we have assessed.

The Norwegian Cancer Plan, Norwegian Official Report no. 1997:20, Care and Knowledge (319) points out that there is evidence of effect of palliative surgery; the literature is characterised by reports based on small and selected series of patients. The Cancer Plan suggests that studies of palliative or symptom-preventing surgery should be a priority in Norwegian cancer care. Moreover, there are no international re-ports that satisfactorily address general issues of indication, effect, or use of resources.

Even after advanced literature searches in the field of palliative cancer, we could only identify a highly limited number of controlled studies of satisfactory quality. This was not an unexpected finding; it was the main reason why the Norwegian Cancer Plan was intended as a stimulus to better documentation of and research into palliation. Re-search results on palliative procedures have generally received less attention than res-ults related to curative methods. Moreover, many will see carrying out clinical re-search related to palliative aims and methods as less meritorious than research aimed at cure. Various methodological problems have also been mentioned, i.e. what qualit-ative or quantitative criteria can or should be used, and how to measure and describe

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them. This is also reflected by the fact that palliative reports generally are of lower quality.

Surgery in Norway is mainly organised according to organ systems. The group of ex-pert includes surgeons with professional backgrounds in five areas in which palliative surgery is routinely considered as an option. Palliative cancer surgery is mainly aimed at prolonging life, relieving symptoms, and preventing symptoms – and the broader, symptom-oriented concept of quality of life. The aim of the treatment is not, as in cur-ative surgery, total resection of the tumour. This may be self-evident; still it is an im-portant realisation that the group of experts thinks make it easier to compare various procedures. It could also provide a required framework for future cost analyses.

2.2The group’s terms of reference

The group of experts shall systematically and critically assess the documentation of palliative surgical interventions in the treatment of cancer patients

The following issues shall be in focus:

Effect – Effect of surgical intervention with palliative intention in terms of prolonging life, relieving symptoms and preventing symptoms. The effect of surgical intervention shall also be assessed in relation to the best supportive care and in relation to alternative therapeutic modalities in those cases when this is relevant.

Consequences – Even though an assessment of methods primarily focuses on clinical aspects, ethical and economic issues shall also be discussed. The use of palliative surgery shall be assessed in the framework conditions of the Nor-wegian health services.

Definition and clarification of the terms of reference – Palliative surgery implies a surgical treatment in which the objective is not cure, but to prolong the patient’s life and prevent or alleviate the patient’s symptoms (NOU 1997:20; 319). The committee is called upon to focus its report on elective sur-gery defined as follows: palliative surgical interventions that may be post-poned for more than 24 hours; palliative surgical interventions in emergencies shall be excluded. “Grey zone” cases shall be discussed in the context of theme. The balance between positive effect and negative effect (complications/death) is interesting and important.

Definition/clarification of the matter under assessment There are many grey zones in therapies that may be curative and palliative at the same time. The main focus in this report is on the treatment of symptoms that are so dis-tressing that non-emergency surgery is assumed to give the best palliation or prolong-ation of life. Therapeutic modalities that strictly speaking are not surgical but which are part of the surgeon’s responsibilities (for example, stenting) are included.

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The clinical course of a cancer patient (figure 3.1) is a result of several factors and the need for palliative treatment may arise at various stages in the chain of treatments. We accentuate three relevant situations in which palliative treatment is an option for pa-tients in advanced stages of cancer:

I. The patient may have had surgery, but has been found inoperable with a curative intention or found incurable without surgery. Surgical palliative treatment could be an option in order to alleviate symptoms or prolong life, for example in advanced prostate cancer.

II. The patient is in need of palliative surgery because of metastasis, for example treatment of a bone fracture caused by bone metastases, in order to keep the func-tion intact.

III. The patient has distressing symptoms from his or her primary tumour and has to have a resection in order to function, for example in cases of obstruction in the central airways caused by cancer.

Figure 3.1. Various clinical courses

Primary oper-able (curative intention)

Potentially cur-ative surgery

Cured Absolutely cur-ative, R0

No surgery

New patient Incurable dis-ease/resection of primary tu-mour

Recidivation R1/R2 resection Tumour-ori-ented

Incurable dis-ease/not tu-mour-oriented surgery

Not tumour-ori-ented

No surgery Not tumour-ori-ented

“Open and shut” cases

Tumour-ori-ented

Surgery

Inoperable Other factors (general condi-tion etc.)

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Tumour-related factors

The task at hand was limited to the following fields:

Gastroenterologic surgery: surgery related to the alimentary tract from the oeso-phagus to the rectum that improves functions, reduces pain or stops bleedings.

Neurologic surgery: surgery because of primary tumour or metastasis to the brain or the spine/spinal medulla in order to preserve neurologic functions.

Orthopaedic surgery: surgery related to pain and/or fractures or required reinforce-ments of arm, leg or spine due to bone metastases.

Thoracic surgery: surgery on metastases in the lungs, reduction of compression of the superior vena cava and procedures and keeps the airways open.

Urologic surgery: surgery related to the urinary tracts in order to provide passage from the kidneys to the urinary bladder, facilitate voiding of the bladder, and stop bleedings.

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3 Method

3.1Mode of work

The group of experts worked in sections organised by field: gastroenterologic, neuro-logic, orthopaedic, thoracic and urologic surgery. The urologic surgery group was re-organised when one member left and a new member was appointed in the middle of the project period. Work on gynaecologic surgery was started but not carried on, mainly because palliative procedures for all practical purposes are directed towards the urinary tracts and the digestive channel and are considered in the relevant sections.

The project manager organised the literature search according to the group’s terms of reference and the plan for the project. Abstracts were retrieved and submitted to the group members.

3.2Literature search

Criteria for inclusion:Interventions

– surgical intervention with palliative intent directed towards the primary tumour– surgical intervention with palliative intent directed towards metastases– not tumour-related surgical palliative intervention

Population– patients to be treated with surgical intervention with a palliative intention

Study design – What is under review is the effectiveness of surgical interventions in palliative

treatment of cancer patients; hence clinically controlled studies should consti-tute the backbone of the review. If possible, these should be

– meta-analyses of randomised controlled trials– randomised controlled trials

The following other types of studies with a lower quality may also be included:– controlled trials of good quality (controlled study with pseudo-randomisation,

non-randomised controlled study (cohort), case-control study)– register data– patient seriesReview articles are included in the literature search only in order to retrieve data from lists of references.

– Measures of effectiveness– Life-prolonging treatment: prolonged lifespan, either absolutely (months,

weeks), or relative improvement in percentage terms.– Symptom-preventing treatment: delayed time to onset of symptoms/recidi-

vation. (The measure of effectiveness here will be time from start of treatment to onset of symptoms.)

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– Symptomatic treatment: reduction of troublesome symptoms, cited as degrees of symptom relief, the proportion of patients with palliation and the duration of this effect. This may to some extent also be measured and objectivised, for in-stance by use of instruments for measuring quality of life or functional status.

Languages – Articles whose quality and relevance may be assessed on the basis of abstracts

in one of these languages: English, German, French, the Scandinavian lan-guages

Time period– Articles from 1966 and onwards

Criteria for exclusion:

Interventions– surgical intervention with a curative intention– emergency surgery– undocumented experimental modalities

Population– children were not included

Study design: Seen as irrelevant were case histories or anecdotes, expert comments, consensus reports, clinical trials of poor quality (e.g. lack of controls, too few patients in relation to the relevant problem etc.) Consensus reports could, however, be useful for ethical assessments.

Articles that only deal with curative treatment were not included. Survival results are cited from included articles that also report data on palliative effect. Only results that are relevant from a palliative perspective on cancer surgery are cited; hence results from all patient groups in an article are not necessarily cited.

Search strategy These bibliographic databases were used: Medline (1966–2000) HTA database (1992–2000) Cochrane Library:

Cochrane Database of Systematic Reviews (CDSR)Cochrane Controlled Trials Register (CCTR)

Database of Abstracts of Reviews of Effectiveness (DARE) Embase (1974–2000) NHS Economic Evaluation Database Cancerlit

Lists of references in relevant article were reviewed in order to identify relevant pub-lications that were not identified through database searches.

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Systematic searches were conducted for each field. Initially a general search was done for advanced disease and palliative surgery for the various cancer diagnoses. This was too unspecific, as treatment aimed at survival was prevalent and the palliative per-spective less pronounced. The report is therefore based on searches in which specific symptoms with a need for palliation were linked to advanced stage of the cancer in question. This compilation was then seen in relation to specific surgical methods. For search strategy, see chapter 12.1, search strategy. QQQ

This search strategy was used for a final updating search conducted 1 January 2003 for randomised studies, meta-analyses and systematic reviews of all the five sub-specialties. The assessment of this literature was finalised on 28 February 2003.

3.3Assessment of the literature

Stage 1 included reading of abstracts that were identified through the searches. Each group had two or three experts. They read and assessed the abstracts independently of each other (table 3.1) and submitted their results to the project manager. Included in the number of articles for orthopaedic surgery are articles that were assessed jointly with the neurosurgeons and were related to metastases to the spine.

Table 3.1. Stage 1: Number of abstracts read by each specialist groupTotal no. of articles of articles

Gastro-enterologic

Neuro-surgery

Ortho-paedicsurgery

Thoracic surgery

Urologicsurgery

Assessed, total

3731 1716 462 277 480 796

Assessed at stage 2

871 365 86 163 90 167

Assessed at stage 3

320 104 20 64 37 95

Excluded at stage 3

157 38 12 21 18 68

Included at stage 3

163 66 8 43 19 27

For stage 2, articles selected on the basis of abstracts were retrieved. Articles that did not meet the criteria for inclusion were excluded at this stage (table 3.1). The experts decided on exclusion according to these criteria: Was the study design irrelevant? Was the patient group irrelevant? Was the intervention badly described? Were the endpoints not clearly defined? Was the study inadequately performed?

At stage 3, each article was thoroughly assessed for inclusion in the basis of literature (table 3.1). The articles were discussed in plenary sessions and notes taken on special types of information considered relevant in each article. Notes were also taken of stat-istical methods used and authors’ conclusions. The articles were checked for internal validity according to check lists for randomised trials, case-control studies and cohort

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studies; they were ranked (table 3.2) and assigned an evidence level (table 3.3). Total evidence level (table 3.4) varied among the fields of surgery.

Articles at stage 3 were excluded because of weak validity; they might also be ex-cluded from the basis of evidence at this stage if the method was badly described or serious bias was not explained. A list was made of these articles with specification of the reason for exclusion (chapter 10).

It was known in advance that there was a limited number of controlled studies (evid-ence level 1 or 2) in the field, hence articles at evidence level 3 were also included in order to develop a survey of the literature available for the wide range of surgical pro-cedure for which an assessment of effectiveness was relevant; hence, best evidence of effectiveness will be at different levels among the fields. For some therapeutic modal-ities there were only small patient series or pilot studies and we cannot give a total as-sessment of the total evidence level in this review.

TABLE 3.2. RANKING BASED OF TOTAL ASSESSMENT OF QUALITYRank Criteria++ Used if all or most criteria in the check list are filled; if the criteria are not

filled: there is a high probability that the conclusions from the study or sur-vey would not change

+ Used if some criteria in the check list are filled; if the criteria are not filled or not adequately described: if the conclusions from the study or survey would probably not change

- Used if few or none of the criteria in the check list are filled; if the criteria are not filled or not adequately described: if the conclusions from they study or survey would be expected to change

Table 3.3. Study types and study quality

Level Study types and study quality

1++ Very good meta-analysis, systematic survey of randomised controlled tri-als (RCT) or RCTs with very little risk of bias

1+ Well conducted meta-analysis, systematic survey of RCT or RCT with little risk of bias

1- Meta-analysis, systematic survey of RCT or RCT with great risk of bias2++ Very good systematic survey of case-control or cohort studies with very

little risk of confounding factors, bias or coincidence and a high probabil-ity that the claimed association is real

2+ Well conducted case-control or cohort studies with little risk of confound-ing factors, bias or coincidence and a moderate probability that the claimed association is real

2- Case control or cohort study with a high risk of confounding factors, bias, or coincidence and a significant risk that the claimed association is not real

3 Not controlled studies (with an element of comparison), register studies, patient series

4 Statements by experts, descriptive studies, case reports

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4 Results

4.1 Gastroenterologic surgery

IntroductionPalliative surgery addresses symptomatic problems and their amelioration. The volume of abdominal surgery seen relation to incidence and median survival is presented by averages for the 1996–2000 period (table 4.1.1).

Table 4.1.1 Survey of the main groups of gastrosurgical cancer in Norway

Organ No. per year1 Operated2 Median survival3

Oesophagus 160 19% Operated: 9 months Not operated: 9 months

Ventricle 650 36% Operated: 18 monthsNot operated: 7 months

Pancreas 590 9% Total 7 months

Colon 2090 >90% Dukes A–C: >5 yearsDukes D: 8 months

Rectum 1000 >90% Dukes A-C: >5 yearsDukes D: 11 months

1 Average incidence 1996–2000. Norwegian Cancer Registry: Kreft i Norge 2000. Rounded off to 10.2 The proportion of resections is the average of resection procedures 1999–2001, Norwegian Patient Re-gistry, SINTEF Unimed, in relation to the average incidence 1996–2000.3 Estimated values from five-year survival curves. Norwegian Cancer Registry: Kreft i Norge 1999.

Below we start with symptoms related to functions in the digestive tract and its adja-cent organs that can be alleviated by gastroenterologic surgery:

1. Dysphagia caused by oesophageal cancer and in some instances tumours/meta-stases that put pressure on the oesophagus from the outside.

2. Icterus caused by a mechanical pinch on the biliary tracts.3. Retention (poor or no passage from the stomach to the small intestine) caused by

cancer in distal biliary ducts, pancreas, or the stomach.4. Intestinal obstruction/ileus caused by stenosis or obstruction or pinch on the in-

testinal tract.5. Intestinal bleeding caused by bleeding from the gastrointestinal tract.6. Pain • Quality of life • Survival

4.1.1 Dysphagia caused by oesophageal cancer

Each year about 160 new cases of oesophageal cancer are diagnosed in Norway. These are often older patients (70+) who not infrequently have comorbidity /led-sagende sykdommer QQQ that are of decisive importance in relation to the choice of relevant treatment.

19

Dysphagia could be a symptom of cancer of the oesophagus or in the cardia. Patients with cancer of the oesophagus and dysphagia at the time of diagnosis are often in an advanced stage of the disease, hence the prognosis is often very serious; total five-year survival is estimated at 5–10%. Surgical treatment with curative intention could be an option for a small proportion of these patients (approx. 20%). The others will often be in need of palliative treatment in order to obtain improved oesophageal func-tioning.

The aim of palliative treatment in this setting is to help the patient to achieve an oeso-phageal function that enables normal intake of fluids and nutrition. At the same time, the procedure-related rate of complications must be low and the procedure should give as little discomfort for the patient as possible.

Available palliative methods include: Surgical treatment Laser therapy

o Laser versus injectiono Laser versus intubationo Laser versus photodynamic treatment

Endoscopic intubation: rigid tube versus self-expanding stent Oncologic non-surgical modalities together with surgical palliative procedures

We have not identified relevant studies according to the above criteria, studies of comparable modalities such as bipolar coagulation or argon plasma coagulation. Fur-thermore, we have not identified studies that compare palliative surgical treatment with purely palliative radiotherapy and/or chemotherapy. Such treatment has, how-ever, not infrequently been given to some of the patients who, in the studies we have evaluated, have been given surgical or non-surgical treatment, a fact that complicates the assessment of treatment effect.

It is a debatable point whether all these methods are “surgical”; in many countries there are often other specialists (medical gastroenterologists, dedicated units for endo-scopy, interventional radiologists etc.) that use such therapeutic modalities. In Nor-way, these patients are by and large treated by surgeons. We still found it appropriate to include these alternatives in this literature review. The methods all have their ad-vantages and disadvantages; below we give an account of the scientific evidence.

Few good prospective studies (RCTs) have been published within the field of gastro-enterologic palliative cancer surgery. In this literature search, only five such studies were identified (2,4,11,50,68); we have also assessed a prospective controlled study (29) that focuses on palliative treatment of dysphagia. By and large the literature can be classified as in the table below:

20

Symptom Type of cancer

Treatment Reference Evidence level

Dysphagia Cancer of the oesophagus

Surgery 47 Segalin 3Laser therapy 2 Alderson

11 Carter29 Loizou1 Ahlquist54 Spinelli 7 Barr12 Carter32 Naveau37 Paolucci

111233333

Intubation/ stenting

50 Siersema68 Adam67Knyrim14 Cowling47 Segalin15 Cwikiel35 O’Sullivan

1123333

Oncologic treat-ment and sur-gery

No relevant literature

SurgeryA retrospective study (47) reports the results after palliative resection of tumour tissue and surgical by-pass; results after intubation and laser treatment are also reported by the same centre. Severe complications after palliative surgery for cancer of the oeso-phagus were frequent, with mortality above 20% after palliative by-pass surgery. The same authors also cite mortality above 10% after intubation. The rate of complications is above 30–40% after various palliative procedures.

Palliative procedures lead to considerable morbidity and mortality, a fact that under-scores the need for alternative, non-surgical modalities for this group of patients with disabling dysphagia and with a severe prognosis.

Laser therapyThree randomised studies compare endoscopic laser treatment with, on the one hand, injections with polidocanol, a cytotoxic agent (4), intubation with latex tubes (2,11), or the use of self-expanding stents (68). The fifth study compares latex tubes with self-expanding stents (50). The studies are by and large small (<40 patients included), but they provide a certain basis for suggesting that by far the most patients who need palliative treatment for their dysphagia can profit from the use of these non-surgical methods.

In three prospective series of patients (1,7,12), the effect of palliative endoscopic laser therapy was assessed. An important palliative effect on oesophageal symptoms was achieved in between 80% and 95% of patients, but a large proportion of the patients had to be re-treated, some of them several times. Although laser therapy is considered as relatively gentle and safe, the numbers of procedure-related complications are not inconsiderable (12).

21

How long the result of the treatment lasts is important to the patient. A retrospective study (22) reports lasting good oesophageal function in about one third of the patients after 3 months and in a little less that one fourth of the patients after 6 months. This underscores the need for repeated procedures in many patients. Palliation of symp-toms was associated with the effect of the first procedure; in patients with longer sten-oses the effect of the treatment did not last as long. It is suggested that a combination of laser therapy and radiotherapy and chemotherapy (12) could further reduce dyspha-gia and improve nutritional status, though there are not good data that substantiate it in this study.

– Laser versus injectionIn one randomised study with few patients (4), endoscopic laser therapy was com-pared with endoscopic local injection of a 3% concentration of the cytotoxic agent polidocanol. In more than 80 % of patients, normalised oesophageal functioning was achieved. Although one patient had an oesophageal perforation after an injection, both alternatives are considered safe and effective. Injection treatment is probably not much used in Norway, as not inconsiderable investments in necessary equipment are needed.

– Laser versus intubationIn two randomised studies (2,11), laser therapy was compared with the use of latex tubes (Atkinson tube or Celestin tube). Good palliation of the dysphagia was achieved in a majority of patients. Laser therapy more often required repeat procedures (2); the weight loss was less in those treated with laser, though this did not translate into im-proved survival (11). The authors conclude (2) that laser therapy is primarily an op-tion in cases of shorter stenoses (<4 cm). These observations are in line with the res-ults of a controlled trial (29) in which good palliative effect was found with both al-ternatives, but better palliation after intubation in distal oesophageal/cardiac stenoses. Perforation after intubation was observed in 13% of patients as compared with 2% after laser therapy. From a retrospective study (37), it was also reported more symp-tom-free days after tube treatment compared with laser therapy and, in total, fewer days of hospitalisation required by the need for repeat procedures. Patient satisfaction was higher among patients treated with tubes but this group had higher mortality (4%) and higher morbidity (10%).

Endoscopic laser therapy (32,37,54) is an efficient method of recanalisation. Between 75% and 85% of patients experienced improvement or elimination of their dysphagia. Some patients needed several treatments for a satisfactory result to be achieved (32). Compared to patients treated with perturbation, laser-treated patients spent signific-antly more days in hospital (37).

Treatment results from two British hospitals were compared in a controlled trial (29). Over the 1987–89 period, 43 patients were treated with endoscopic laser (in London) and 30 patients with endoscopic intubation with the Atkinson tube (in Nottingham). For smaller thoracic oesophageal tumours, the percentage of patients achieving im-provement of their dysphagia was high (95–100 %) and just as good with both modal-ities. Patients with distal stenoses/tumours had significantly better effect from intuba-tion than from laser therapy. The perforation rate was lower in the laser-treated group (2% vs. 13%). The authors emphasise that for individual patients the two techniques should be regarded as complementary.

22

The literature in this field is to a large extent comprised of retrospective studies based on single-centre data. Quite often, the criteria used for choice of treatment are not presented explicitly, and not rarely patients have received other oncologic treatment such as chemotherapy or radiotherapy in addition to the specific palliative sympto-matic therapy (stenting, intubation, or laser). The selection of patients and specifica-tion of complications are problems in retrospective studies. The scientific publications are relatively rarely based on prospective studies; randomised trials are even rarer. Given these deficiencies in documentation, it is hard to draw firm conclusions.

– Laser vs. photodynamic therapyFrom a study (54) of malignant obstruction in the upper as well as the lower gastrointestinal tract one may extract results from a group of patients (with upper gastrointestinal obstructions) who underwent laser or photodynamic therapy. The group was heterogeneous and the study is hard to evaluate. Recanalisation was achieved in most patients and subjective palliations of symptoms in three quarters of patients (both groups included). No deaths were related to the endoscopic treatment.

Intubation/stenting– Use of self-expanding stentDuring the last few years, treatment with self-expanding stents has been generally available for clinicians and has contributed to giving more patients a palliative non-surgical alternative. It is maintained that stenting extends the palliative measures that can be offered to the patients in question beyond what can be achieved or is technic-ally feasible with latex tubes (48). Several different types of stents with larger or smaller differences are on the market; their use varies from country to country and from clinic to clinic. Given the fact that several different types of stents are used on to some extent heterogeneous series of patients, comparisons and assessments of results are exceedingly difficult to make.

Stenting is done endoscopically, with or without x-ray imaging, usually under total anaesthesia. Self-expanding stents have a very good palliative effect in more than 95% of patients (14,67,68). Good information about the course of the disease in pa-tients after stenting is often lacking. However, one study (14) found that 9% of pa-tients had recurrent distressing dysphagia after on average 22 weeks. Procedure-re-lated mortality was considered low (2–10%).

More recent studies (14,15,35) have shown that stenting provides good palliation of dysphagia in 9 out of 10 patients, with low procedure-related mortality and morbidity. Still it should be noted that the rate or complication is given as between 20% (35) and 45% (15), and procedure-related (thirty-day) mortality between 1% and 6% has also been observed (35,48). Long-term results from these studies are lacking; still it is clear from relatively short observation periods that some patients are in need of re-treatment because of tumour ingrowth into the stent, or overgrowth (14). In order to reduce ingrowth, plastic-covered stents have been introduced. This clearly reduces the risk of ingrowth, though it substantially increases the risk of stent migration (68). The attending physician should assess each patient individually and take a number of factors into account – type of obstruction, its length and level, fistula problems, the range of application of the stent, and costs.

23

– Placement of a tube in the oesophagus: rigid tube vs. self-expanding stentWe have identified only two randomised prospective studies (50,67) that compare stenting with intubation. There were substantially more major complications in the group receiving latex tube prosthesis. Thirty-day morality was twice as high (29% vs. 14%) in the group that was intubated (67). More than a fourth of the patient in both groups had recurrent dysphagia because of tumour growth or tube migration. Prior ra-diotherapy or chemotherapy increased the risk of complications, especially among those who were intubated (43% vs. 17%) (50). The two methods may be seen as com-plimentary. The introduction of self-expanding stents has enhanced the therapeutic options for patients with malignant dysphagia (48).

Oncologic non-surgical therapeutic modalitiesNo relevant literature was identified.

ConclusionConsiderable morbidity and mortality is associated with surgical palliative treatment in these patients. Non-surgical methods such as endoscopic stenting or laser therapy should be preferred, as both methods give a rapid and relatively good palliation. Laser therapy must often be repeated in order to maintain the oesophageal function.

4.1.2 Icterus

Symptom Type of can-cer

Treatment Reference Evidence level

Pruritus because of an obstruction

Pancreatic can-cer

Surgery vs. stenting

55 Taylor3 Andersen8 Bornman49 Sheperd51 Smith

1+1+1+1+1+

Percutaneous vs. endoscopic stenting

53 Spear 1-

Quality of life Pancreatic can-cer

Stenting 30 Lumen 3

Palliative treatment of pruritus

Obstructive icterus caused by malignant disease occurs in about 70% of patients with pancreatic cancer (expanding from the exocrine part of the pancreas) (25). In patients who cannot undergo surgery with a curative intention, palliation of pruritus related to icterus is one of the most important objectives. If pruritus can be treated effectively in other way, or if pruritus initially is not a prominent symptom, it is not clear whether treatment for icterus is of any substantial importance for other symptoms such as nausea, weak appetite or general well-being.

Quality of lifeIn a prospective institution-based study using validated methods (EORCT QLQ-C-30) in order to assess quality of life before and 28 days after stenting for obstruction (due to malignant extrahepatic structure) in biliary tracts, it was found considerable relief

24

of symptoms such as icterus, pruritus and diarrhoea but also a small but statistically significant improvement in relation to tiredness, sleep or appetite. On a functional scale there was statistically significant improvement in emotional and cognitive func-tions and global health (30). The study did not include controls, hence it is hard to as-sess how big an effect the treatment of primary symptoms such as icterus and pruritus had on other symptoms.

Surgery vs. stentingTreatment of obstructive icterus caused by malignant disease can be done by surgical bypass or by stenting the obstructed area. Four randomised controlled trials were pub-lished over the 1986 to 1994 period comparing stenting with surgical bypass (3,8,49,51). One of these trials (8) has a transhepatic placed stent as one arm, the other trials endoscopically placed stents. The success rate, defined as normalised or nearly normalised bilirubin, varied in the stenting groups from 84% to 94% and in the sur-gical bypass groups from 76% to 92%, not a significant difference. Thirty-day mortal-ity varied in the stenting groups from 8% to 20%, in the surgical bypass groups from 13% to 27%. The rate of complication varied in the stenting groups from 28% to 36%, in the bypass groups from 32% to 58%. Only in one of these trials were procedure-re-lated mortality (but not 30-day mortality) and the frequency of serious complications significantly lower in the stenting group (51). Recurrent icterus requiring hospitalisa-tion was, when specified, more frequent in the stenting groups. Median survival after treatment varied in the stenting groups from 12 to 22 weeks and in the bypass groups from 14 to 26 weeks.

In a meta-analysis (55) of three RCTs (3,49,51) with endoscopically placed stents as one arm, it was found that the odds ratios for treatment failure and serious complica-tions were so heterogeneous that a common odds ratio could not computed. Thirty-day mortality was the same in the stenting and bypass groups. More retreatment ses-sions were necessary in the stenting groups assessed by odds ratio and confidence in-terval.

These trials have been criticised because of high mortality in the surgery groups. Two large retrospective studies from specialised high-volume centres report mortality in surgical bypass of 2% and 3.3% and procedure-related morbidity of 32% and 27% (25,59). This patient material is, however, not comparable with those of the prospect-ive studies summarised above. Patients undergoing surgery in these studies were largely operated with an initially curative intention. This means that the preoperative evaluation had not documented definitive criteria for surgical treatment (criteria for inoperability), hence it is probable that the risk profile in this group of patients was different because of less advanced diseases. In a large Norwegian population study, it was found a procedure-related mortality of 12.4% and a morbidity of 24% for this type of surgery (5).

Percutaneous vs. endoscopic stentIn a published randomised controlled trial (53), percutaneously transhepatically placed stent was compared with endoscopically placed stent. The success rate (ad-equate bilirubin decline) was 61% in the group with stenting done in open surgery and 81% in the group with endoscopically placed stent, a significant difference. Thirty-day mortality was also significantly different; 33% in the group with percutaneously placed stent and 15% in the group with endoscopically placed stent.

25

Type of surgeryIn the largest systematic review article published on palliative surgical procedures in pancreatic cancer, risk of recurrent icterus was estimated at above 10% after cholecys-toenterostomy (95). More than 10 000 patients were included. In a large retrospective series of patients (17), recidivation of icterus was observed in 12.8% of patients un-dergoing choledochoenterostomy and in 21.4% of those undergoing cholecystoentero-stomy. There are no controlled studies focusing on this problem.

A major prospective population study reports procedure-related mortality from cholecystoenterostomy of 13.5% and 12% from of choledochoenterostomy (33). The large systematic review article cited above (95) also did not identify a difference in procedure-related mortality from cholecystoenterostomy compared with chole-dochoenterostomy.

4.1.3 Retention in pancreatic cancer

Symptom Type cancer Treatment Reference Evidence level

Obstruction Pancreatic can-cer

Gastroentero-stomy (simple bypass)

Espat on need

22 Gough38 Potts44 Sarr19 Espat

3333

Nausea and vomiting

Pancreatic can-cer

Simple vs. double bypass

28 Lillemoe51 Smith44 Sarr16 de Rooij22 Gough52 Sohn

1+1+2+333

Need for treatment In one case-control series and two non-prospective patient series about pancreatic can-cer, the frequency of surgery needed for treatment for ventricle retention varied from 10% to 15% (22,38,44). In contrast to these studies, there is a published retrospective study from a high-volume centre on pancreatic cancer patients in which laparoscopic staging was used as the last step before potentially curative surgery. Out of the 155 patients who were inoperable after this procedure, only 3 (2%) needed relieving gast-roenterostomy over the course of their remaining lifetime (19).

Single vs. double bypass in cancer of the distal biliary ducts and the pancreas Nausea and vomiting are prominent symptoms in up to 50% of patients with malig-nant disease in the distal biliary ducts and the pancreas. The frequency of mechanic obstruction, diagnosed by x-ray examination or endoscopy as the reason for this, is unknown, but probably applies to far less than half of the cases. One randomised study is published, done in a high-volume centre, that compares routine biliary bypass combined with gastroenterostomy to biliary bypass alone (28). Only patients with no significant risk of developing an obstruction of the duodenum were included, though this is not specified with objective criteria. No difference in median survival was found after, respectively, 8 months after double bypass and 6 months after single bili-ary bypass. Procedure-related morbidity was 33% and 32% respectively, and there

26

was no procedure-related mortality in any of the groups (28). It was found that the risk of developing ventricle retention needing treatment was 19% with only biliary bypass, while no patients developed ventricle retention after double bypass.

In the surgical arm of a randomised study designed to investigate the effect of stenting vs. surgery for obstructive icterus (51), 18% of patients operated with simple bypass developed ventricle retention, while the corresponding frequency for patients operated with double bypass was 2% (a significant difference).

A well-balanced case-control study showed the same mortality in both groups (44). Three large retrospective patient series cite mortality from such procedures varying from 0 to 14%; no difference was established between simple and double bypass (16,22,52). Procedure-related morbidity varied from 1% to 15–30% and was approx-imately 10% higher (a significant difference) in double bypass than in single bypass in two studies (16,52).

ConclusionStenting or surgical bypass has the same effect in obstruction of the biliary ducts. Rate of complications after these procedures are relatively high.

4.1.4 Retention and/or bleeding in cases of gastric cancer

Symptom Type of cancer

Treatment Reference Evidence level

Retention and/or bleed-ing

Gastric cancer Complete or par-tial gastrectomy

23 Haugstvedt60 Bonenkamp18 Doglietto36 Ouchi

3333

Less than 40% of patient with gastric cancer can undergo potentially curative surgery. No studies have been found that provides objective data on improved quality of life, if any, after surgical palliative procedures. A large Norwegian prospective population study, in which 503 patients received palliative treatment, compares procedure-related mortality and survival in patients who had undergone various form of gastric resection with patients who underwent various other types of treatment (non-resective proced-ures) (23). No difference in procedure-related mortality was found in these two groups, 13% and 14% respectively. In a subgroup of patients of the same age (70) and the same preoperative weight loss, a doubling of median survival was found in stage III as well as in stage IV in favour of resection. A large number of the patients under-going resection, 64 out of 182, underwent total gastrectomy. Procedure-related mor-tality from gastrectomy in this study (12%) was not different from that of distal resec-tion (11%). This is in keeping with observations from a large prospective population-based study from the Netherlands (60), in which 285 out of a total of 995 patients had non-curable disease when undergoing laparotomy. Out of these, 152 patients under-went partial (31%) or total (22%) gastrectomy and 133 patients only bypass (20%) or exploration (27%). The magnitude of the disease was the decisive factor determining whether resection could be done. Postoperative mortality (in-hospital mortality) was low among those who only underwent exploration (5%), but somewhat higher and quite the same for the groups that underwent bypass (14%) or resection (10–11%).

27

Median survival after palliative resection (8.5 months) was statistically significantly better (p<0.002) compared with exploration only, or bypass (5.5 months).

A major retrospective study (18) gave fundamentally the same conclusion: all patients were in stage IV; no difference in procedure-related mortality could be established between resection procedures (11.8%) and bypass (10.2%). Mortality in total gas-trectomy was 13.1%. Statistical analysis revealed that resection is independently asso-ciated with better survival. Median survival in the resection group was 16.3 months vs. 7.1 months in the bypass group. Local metastasis /spread QQQ was significantly more pronounced in the resection group, but all were in stage IV at the start of the study.

A retrospective study from Japan underscores the importance of peritoneal dissemina-tion for postoperative survival after hospitalisation and total survival (36). In cases of distal ventricle resection and total gastrectomy, two-year survival with peritoneal metastasis /bukhulespredning/QQQ near the primary tumour was, respectively, 28% and 18%. In cases of disseminated peritoneal metastasis, two-year survival with distal resection was 17 % and with total gastrectomy 0%. Out-of-hospital survival for more than 3 months was observed in 83% of patients after various type of gastric resection, in 33% of patients after gastrojejunostomy, and in 56% of patients after explorative laparotomy only.

ConclusionIf gastric cancer cannot be treated with a curative intention, there is still a certain amount of documentation to the effect that gastrectomy (total or partial) under certain conditions could contribute valuable palliation through longer survival, prevention of serious bleeding and removal of a relative obstacle in a passage.

4.1.5 Intestinal obstruction

Symptom Type cancer Treatment Reference Evidence level

Intestinal ob-struction

Colorectal or gyn-aecological cancer

Surgical 20 Feuer43 Sarela9 Branum13 Clarke-Pearsons

3333

Non-surgical; i.e. laser ther-apy, cryo-therapy or stenting

10 Camunez65 Lobato34 Orth54 Spinelli

3333

Intestinal obstruction as a consequence of a primary or metastatic tumour is an im-portant problem in gastroenterologic surgery. Colorectal or gynaecologic cancer is the main cause of obstruction of the small intestine as well as the colon.

Twelve studies that deal with this topic have been identified. Eight of these studies are non-prospective patient series (evidence level 3), while three studies are prospective institutionally-based patient series (evidence level 3). None of these studies have ad-

28

equate control groups, though one study (54) compares the effects of laser therapy on the upper or lower intestinal tract. The Cochrane Library published a review of the lit-erature on this topic in 2000 (20).

SurgeryFeuer´s review article (20) deals with malignant obstruction in advanced gynaecologic and gastrointestinal cancer. The total number of patients in the studies included cannot be determined with exactness; an estimate would be 1500 patients. Included were studies that comprised the following specific post-surgical data: on morbidity and mortality, palliation of symptoms, rate of re-obstruction, and quality of life. Most of the studies are of ovarian cancer. There are no data that throw light on a possible dif-ference between gastrointestinal and gynaecologic cancer. None of the studies was of a quality that allowed statistical analysis; consequently the review article only presen-ted a qualitative analysis. There were considerable differences in the definition of symptoms as well as palliation. The inclusion criteria in the 14 studies were also very different. Control of symptoms was achieved in between 42% and 80% of patients. Thirteen retrospective studies include re-obstruction rates, but data on time interval before re-obstruction are lacking in most of these studies. Re-obstruction rates are given as between 10 % and 50%. Two studies specify median time to re-obstruction of, respectively, 106 days and 2 months Twenty-two retrospective studies included data on mortality and morbidity. The definition of both variables varied considerably and thirty-day mortality was given as 5% to 32%. None of the studies included data on quality of life.

One study (43) is a prospective observational study QQQ of 24 patients (average age 70) with stage 4 colorectal cancer without symptoms of obstruction. Patients were treated with chemotherapy and followed up in relation to need for later surgery. The primary tumour was localised in the descending colon in 8, in the transverse colon in 1, in the sigmoid in 8 and in the rectum in 7 patients. Median survival was 10 months. Four patients with cancer of the sigmoid developed symptoms of obstruction. Two of these underwent surgery without complications and 2 were stented after 1, 3, 12 and 20 months from the time of diagnosis. A further 3 patients underwent right-sided hemicolectomy because of pain, but did not achieve palliation. One patient had a po-tentially curative rectal and liver resection after successful chemotherapy.

Two studies deal with purely operational treatment with traditional surgery. In Branum’s study (9), 42 patients with non-radical resection (bypass and/or debulking) of metastases to the intestine from malignant melanoma were compared with 36 pa-tients with radical resection. There was no operative mortality; median survival was 7 and 17 months respectively. For the whole group, 92% experienced reduction of symptoms such as pain, obstruction or breeding, while all patients who underwent radical resection had a symptomatic effect. Neither the course of the disease nor pre-operative clinical status could serve to predict the end result. Clarke-Pearson’s study (13) included 49 patients with intestinal obstruction (small intestine 30, colon 16, combined 3) after ovarian cancer. Major complications (not defined in more detail) occurred in 49%; 14% died within 30 days of surgery. 73% of patients survived more than 60 days post-surgery, a median estimated survival of 170 days. The material was worked up by statistical analyses of survival such as Kaplan-Meier analysis, Cox ana-lysis as well as a univariate logistic regression analysis. One found that clinically es-tablished ascites increased the risk of postoperative complications and mortality. With

29

no ascites, survival could be more than 60 days. Correspondingly, preoperatively re-duced nutritional status and clinically advanced tumour status increased postoperative mortality and reduced survival, less than 60 days.

Non-surgical therapy: laser, cryotherapy, or stentingSeven studies deal with non-surgical therapy of the distal part of the colon and/or ob-struction of the rectum. Five of these deal with laser therapy, 1 with cryotherapy and 1 with stenting.

Over a four-year period, Camunez (10) selected 80 out of 173 patients with suspected malignant obstruction of the colon for treatment with self-expanding stents. The tu-mour was in the passage between rectum and colon in 31, in the sigmoid colon in 41, and in the distal part of the descending colon in 8. Average age was 69 (36–96). The stenting was done by radiologists with x-ray imaging but without sedation or anaes-thesia. The procedure was successful in 70 out of 80 patients (88%), imaging aver-aged 31 minutes; in 67 out of 70 patients the procedure was clinically and radiologic-ally successful. There were 4 perforations, 2 of them uncomplicated as the stent covered the perforation, 2 underwent laparotomy of whom one died of myocardial in-farction postoperatively (procedure-related mortality 1.3%). 33 patients underwent elective surgery after on average 7 days, 35 patients kept their stents as final therapy. 91% of the stents remained open after 3, 6 and 9 months. Average survival was 147 days (span:125–169 days).

Over a four-year period, Lobato (65) included 41 patients with clinical symptoms of obstruction from 2 days to several months before hospitalisation. In one patient, the obstruction was in the left colic flexure, in 17 in the sigmoid colon, and in 23 in the rectum. In all patients the placement of a self-expanding stent was successful and un-complicated. In 38 (93%), the stent did away with the symptoms. Two patients later underwent an ostomy. When the study was closed, 80% of the patients had died, on average after 4.5 months (span 1–18 months).

Over the ten-year period 1982-1991, Orth (34) treated 182 out of 855 patients with rectal cancer with cryotherapy, applied with two to four days’ intervals until results were achieved. Average patient age was 74; 71 received cryotherapy because of gen-eral inoperability, 41 because of tumour-related inoperability, 18 because of local re-cidivation, and 17 because of a combination of general and tumour-related inoperabil-ity. There was one perforation among those with tumour-related inoperability; com-plications in the form of bleeding, stenoses, incontinence and a need for relieving os-tomy occurred in 4% to 15% of the cases. For the individual symptoms of tenesmus, secretion of mucosa, leaking haemorrhage, larger major haemorrhage and perineal pain, lasting therapeutic effect was achieved in 51%, 53%, 24%, 0% and 33% of the cases. 63% of the patients survived for one year, 27% for two years, and 14% for three year after the therapy. Differences in survival between the various groups cannot be extracted from this study.

Five studies present the results of laser therapy for distal colorectal cancer. Patient materials are relatively homogenous with an age span of 72–80 and with a proportion of rectal cancers of 60% to 95%. A total of 877 patients were included. In all studies advanced cancer was the main indication; medical and age-related indications as well as patient preference were of less importance for the choice of therapy. Median sur-

30

vival was about seven months. In all studies patients received repeated out-patient therapy sessions; in haemorrhage, diarrhoea and obstruction were cited as main prob-lems. The endpoints are not easily comparable and the difference between immediate and durable effect is also not always clearly defined. Immediate effect was achieved in 82–97%, while effective long-term palliation varied between 41% and 88%. Mor-tality varied from 0 to 2.3% with a total of 12 procedure-related deaths (mainly in-testinal perforation) among 877 patients (1.4%). Complications varied from 3% to 15%, but they are not directly comparable.

Taken together, these five studies show that repeat out-patient therapy sessions give a good palliative short-term and long-term effect in advanced inoperable distal colo-rectal cancer, with low mortality and rate of complications. The effect on the various symptoms varies somewhat from study to study, though generally short strictures and primary tumour are good predicators of a positive result.

ConclusionObstruction of the intestine in cancer is relatively frequent and requires palliative gastroenterologic surgery. The degree of control of symptoms achieved varies a great deal; 50% of patients develop a new obstruction within 2 to 3 months.

4.1.6 Intestinal bleedings

Symptom Type of cancer

Treatment Reference Evidence level

Bleeding or obstruction

Cancer in the distal part of colon or rectum

Laser 21 Gevers31 Mesko45 Schulze54 Spinelli57 van Cut-sem

33333

Cryotherapy 34 Orth 3

Six retrospective series of patients, and all the 12 studies that are also reviewed under gastrointestinal obstruction, describe bleeding from cancers of the distal colon and, mainly, the rectum. None of these studies have control groups. All studies cite number of patients with bleedings as the main or partial QQQ symptom. The proportion with bleeding and obstruction as their main symptom varies considerably, but bleeding seems to represent as great a problem as obstructions in terms of numbers. Spinelli (54) (n = 86+52), Mesko (31) (n = 34), Schulze (45) (n = 27), van Cutsem (57) (n = 18+21) and Gevers (21) (n = 76) used repeat out-patient laser therapy sessions with 92 to 100% initial therapeutic effect. The long-term effects were, however, considerably worse.

In Spinelli’s study (54), half of the patients developed a new bleeding over the course of a follow up period of median 11 weeks. However, Gevers (21) reports long-term palliation in 83; the 3 other articles have no data on long-term effect. In the light of the patients’ short expected remaining lifespan (median 7 months), the results of out-patient laser therapy seem to represent an alternative for relevant patient groups.

31

Only one study (34) reports results from cryotherapy. A temporary effect was achieved in 28 out of 47 patients, while long-term effects were only observed in 9 pa-tients (19%). Cryotherapy was also carried out on an ambulatory basis.

None of these studies report specifically on complications related to patients with bleeding as their main or a partial QQQ symptom, but these are hardly different from the total material (3–15%).

ConclusionLaser therapy or cryotherapy can be used as an alternative to surgery that is often more comprehensive in cancer of the rectum or the distal colon. Stenting is also an al-ternative. The documentation on effect is, however, weak.

4.1.7 Pain • quality of life • prolongation of life

Symptom Type of can-cer

Treatment Reference Evidence level

Pain Gastric cancer No relevant studies

Pancreatic can-cer

Injection of alco-hol in the celiac plexus

26 Lillemoe 3

Cancer of the biliary ducts

No relevant studies

Colorectal can-cer

No relevant studies

Quality of life Gastric cancer No relevant studiesPancreatic can-cer

Radical surgery, possibly com-bined with ad-juvant therapy

6 Bakkevold24 Huguier27 Lillemoe52 Sohn

3333

Cancer of the biliary ducts

Stent 30 Luman 3

Colorectal can-cer

Laser 21 Gevers 3

Prolongation of life

Gastric cancer Resection 23 Haugstvedt56 Valen36 Ouchi

3

33

Pancreatic can-cer

Injection of alco-hol in the celiac plexus

26 Lillemoe24 Huguir

33

Cancer of the biliary ducts

No relevant studies

Colorectal can-cer

Resection 41 Rosen43 Sarela46 Scoggins

333

In a special section we have chosen to focus on pain and quality of life on the basis of the reviewed literature on palliative gastroenterologic cancer therapy. It is, moreover, a point to look into possible effects on survival of palliative measures, which in point of principle are more directed towards the patients’ symptoms and pain.

32

Gastric cancerIn a large Norwegian multicentre study (n = 1165 patients) of surgical treatment, pa-tients with gastric cancer QQQ (23), 503 patients underwent non-curative therapy (35% resection/gastrectomy, 14% bypass, 31% explorative laparotomy, 16% no sur-gery). On the basis of multivariate analyses the authors conclude that resection doubles survival (stage III, 9 vs. 4.5 months; stage IV, 6 vs. 3 months) when controls are made for age and pre-operative weigh loss. In another report based on the same patient material (56), it was found that there were big differences among regions between various types of hospitals (university clinics, regional hospitals, county hos-pitals) in patient characteristics and the type of treatment used. This point highlights the problem of patient selection.

Survival and quality of life (including ”out-of-hospital survival”) have been focused on in a study from Japan (36), after palliative surgery on patients with gastric cancer (11.5% of all those who underwent surgery for gastric cancer over a seven-year period) with varying degrees of peritoneal metastasis. Survival and ”hospital-free sur-vival” for three months or longer was significantly better in patients who underwent gastrectomy compared with gastrojejunostomy. In patients with marked peritoneal metastasis (P2/P3), neither palliative gastrectomy nor gastrojejunostomy had any pos-itive effect on survival or quality of life. Pancreatic cancerA possible palliative effect from ”radical” pancreatic surgery has for long been dis-cussed. ”Palliative pancreatico-duodenectomy” is often used when postoperative mor-phologic examination of samples from the surgery shows that the procedure was not radical (residual tumour tissue, microscopically or macroscopically, R1 procedure). As shown in a Norwegian multicentre study (6), (the radically operated patients had the best functional status, reasonably enough as it must be assumed that these patients were good candidates for extensive surgery. In this study it was observed that bypass-operated patients (not tumour-directed surgery) were more in need of strong anal-gesics; they were also more afflicted by nausea and vomiting than those who had un-dergone radical surgery. There was no difference in palliative effect between simple or double bypass.

In another large study (24) it is also observed significantly better survival in radically (tumour-oriented) operated patients without metastases compared with those operated with bypass; it was a significant difference in postoperative mortality, 10% and 15% respectively. Based on a retrospective review of 64 patients, Lillemo et al. (27 ) are also of the view that radical pancreatic surgery has a palliative role. In their study, pa-tients had also undergone chemotherapy and radiotherapy. Another study from the same institution (52) reports that palliative surgery could be carried out with a mortal-ity of 3.1%, not significantly different from that among the radically operated (1.9%); the postoperative rate of complications was significantly lower (22%) among the pal-liatively operated compared with radical surgery (35%). It is worth noting that 75% of patients had the celiac plexus blocked as palliative therapy.

Chemical splanchnicectomy with alchohol injection in the celiac plexus has been used in patients with pancreatic cancer. A prospective randomised study (26) has clearly demonstrated that this therapy is efficient for treating or preventing pain in patients

33

with non-resectable pancreatic cancer. Significantly better survival is also demon-strated in patients who had a blockade. It is not known to what extent this therapy is used for this group of patients in Norway.

Biliary ductsPatients with extrahepatic cholestasia with icterus and pruritus will often profit from stenting. A quality of life study including 47 patients (30), confirmed that stenting had a significant and positive effect on icterus and pruritus. Through the use of quality of life instruments (EORCT QLQ-30, GHS), it was also observed that these patients ex-perienced a significant improvement in relation to appetite, diarrhoea and sleep. Emo-tional, cognitive and global health scores were also significantly improved.

Colorectal cancerFor patients with colorectal cancer, other palliative measures than surgery should ne-cessarily be considered and possibly be carried out. A retrospective study (21) of more than 200 patients with inoperable colorectal cancer assessed the benefits of en-doscopic laser therapy in terms of effect on the obstruction, bleeding or other ailments (soiling, diarrhoea, tenesmus). Primarily, 92% achieved a good palliative effect for their main symptom and there were no differences between the three groups. Good long-term effect was achieved in 83% of patients, with the lowest effect (65%) in pa-tients with symptoms of obstruction. This group also had the highest number of re-peated laser therapies. Procedure-related mortality was <3%, and there were relatively few complications (perforation, fistula, abscess, bleeding). Laser therapy may be ef-fective in some patients, but selection of patients is necessary (see page 25).

Patient with advanced colorectal stage IV cancer at the time of diagnosis have a seri-ous prognosis, also in the short term, and ambitions for treatment could be controver-sial. In a recently published study from the USA (41), it was found in a retrospective review of a patient material that median survival was 14.4 months, five-year survival only 10%. Advanced age (>65), carcinomatosis and pronounced/bilobular metastases to the liver were associated with low survival and higher postoperative morbidity and mortality. The authors conclude that resection of the primary tumour and surgery for metastasis should be offered to some of these patients who in this way could still get a better prognosis.

Sarela et al. (43) focused on the same group of patients but they also assessed the ir-resectable synchronous metastases. In this study, 24 patients with advanced colorectal cancer were primarily treated with 5-FU based chemotherapy without other palliation. Median survival was 10 months, one-year survival 44%. The authors conclude that patients with minimal symptoms from their stage IV disease only have a small risk of development of new or more symptoms or complications before they die from their disease. A similar conclusion may be dawn from a retrospective study (46) of 23 asymptomatic patients with advanced colorectal cancer who primarily were treated with chemotherapy or a combination of radiotherapy and chemotherapy. Two patients (8%) had to have a gastric relief /tarmavlastning/QQQ during the course of their dis-ease.

It would seem that in stage IV patients with few or minimal symptoms of their colorectal cancer, surgical treatment does not seem to improve or prevent symptoms

34

or offer a better prognosis. Other palliative measures should be considered when this is deemed necessary on the basis of the clinical issue involved (43,46).

ConclusionPain, prolongation of life, and survival are important aspects in the assessment of pal-liative cancer surgery, but the literature is very limited. Palliation in inoperative pan-creatic cancer can be achieved though injection of alcohol in the coeliac plexus. The quality of live is improved by fewer symptoms of icterus, pruritus, obstruction and bleeding in the bowel.

4.2Neurosurgery

Effect of palliative surgery on patients with cerebrospinal malignant tumour

This report deals with three categories of patients that belong under neurosurgery:1. Primary intracranial tumours, i.e. anaplastic astrocytoma or glioblastoma mul-

tiforme, which constitute the greater proportion of malignant gliomas.2. Metastatic intracranial tumours.3. Metastatic intraspinal tumours; this area is shared with orthopaedic cancer sur-

gery and is considered in the chapter on orthopaedic surgery.

4.2.1 Quality of life, neurologic deficiency /svikt/QQQ and survival in primary cancer of the brain

Symptom Type of cancer

Treatment Reference Evidence level

Survival:1. Determine histologic dia-gnosis2. Relieve signs and symptoms of increased in-tracranial pressure3. Prolong survival

Glioblastoma multiforme

Surgery: Biopsy or resec-tion (total or par-tial)

105 Simpson109 Jeremic111 Stummer107 Kreth108 Kiwit110 Deveaux

1+2+3333

Better quality of life

Glioblastoma multiforme

BiopsyResection (total or partial)

107 Kreth111 Stummer108 Kiwit110 Deveaux

3333

Effect of surgery on average survivalThe therapy for this group of patients usually includes some form of surgery: biopsy or resection of the tumour, either total or partial, followed by some form of oncologic postoperative therapy, usually radiotherapy, the primary therapeutic alternative.

35

Surgery for gliomas has three main objectives:1. Determining histologic diagnosis2. Relieving signs and symptoms of increased intracranial pressure3. Prolonging survival and achieving a better quality of life

There is general agreement on the use of surgery for objectives 1 and 2. Sometimes it is clear that either a simple biopsy or radical resection should be done. Resection is relevant when there are clear clinical signs of increased intracranial pressure, or redu-cing the size of the tumour (cytoreduction) is necessary. However, if the tumour is located in an area of the brain that is difficult to access or a resection would cause sig-nificant neurologic symptoms postoperatively, biopsy is clearly the best choice. Objective no. 3 above is still controversial, as the majority of patients are in a grey zone in which there does not seem to be sufficient information on which procedure will give the best quality of life or prolong survival.

Simpson et al, (105) brought together data on individuals from three trials with 645 patients with glioblastoma multiforme. These were randomised controlled trials of either dose-response effects in radiotherapy or benefit from chemotherapy combined with radiotherapy. No significant difference in median survival was found between the treatment groups, hence the data could be analysed combined. Total resection res-ulted in a clearly longer survival compared to biopsy (11.3 vs. 6.6 months). Both groups of patients were also given radiotherapy. It was also found that resection gives longer survival when compared to biopsy (10.4 vs. 6.6 months). Similar results are reported from several other retrospective studies: Deveaux et al. (110), Kiwit et al. (108), and Jeremic et al. (109).

In a study reported by Stummer et al. (111) on 52 patients in whom an intraoperative method was used to establish the scope of tumour resection, total tumour resection gave significantly increased average survival compared with partal resection of the tu-mour.

In a retrospective study, Kreth (107) reported no significant difference in survival between resection and biopsy. Patients who underwent biopsy were assessed as in-operable or in such severe neurologic condition that the risk associated with surgery was too great. In spite of this they did as well as the group that had their tumours re-sected.

Similar results that raise some doubt as to the effect of tumour resection on survival, at least in glioblastoma multiforme, were reported in two review articles that were not included here (117,119). No studies fulfill the Cochrane RCT requirement (113).

Effect of cytoreductive surgery on quality of lifeAll publications mentioned used median survival time as the main measurement of ef-fect of biopsy vs. cytoreductive surgery. Quality of life of patients was not assessed in detail, but five studies used Karnovsky Performance Scale (KPS) in order to assess the functional status of patients.

Several studies show that KPS is an important predictor of survival (106,108,110, 111). Kiwit presents results from pre- and postoperative measurements and finds no

36

improvement in patients that underwent biopsy. In contrast, Kreth et al. (107) showed in a retrospective series of patients that six weeks after treatment there was no differ-ence in clinical status between resection and biopsy.

ConclusionSetting the histological diagnosis: This is generally done by biopsy. On the other hand, stereotactic biopsy underestimates the diagnosis of glioblastoma multiforme vs. anaplastic astrocytomas compared to resection, with resulting bias towards the biopsy patients. This is the situation, given that glioblastoma multiforme patients who are er-roneously diagnosed as having anaplastic astrocytomas have a worse prognosis than what would be expected (112).

Mild signs and symptoms of increased intracranial pressure: Cytoreductive surgery gives an obvious improvement and should be carried out.

Prolonged survival and better quality of life: Cytoreductive surgery seems superior to biopsy in terms of prolonged survival as well as quality of life. All publications that found only a small difference between biopsy and partial resection compared to total resection were based on the surgeon’s own assessment of the degree of residual tu-mour. This method has been proven to be highly unreliable, as the surgeon almost al-ways underestimates the amount of residual tumour tissue. In the two reports in which an objective measurement of residual tissue was carried out (109,111), radical resec-tion turned out to be definitely the best alternative. Radical resection usually does not lead to deterioration of neurologic status and often improves it compared to partial re-section; it should be the preferred choice.

4.2.2 Neurologic deterioration and survival in brain metastasisSymptom Type of

cancerTreatment Reference Evidence

levelProlongation of life. Reduced neurologic symptoms.

Various types of primary can-cer

Surgery and ra-diotherapy vs. biopsy and radio-therapy

104 Vecht106 Patchell

1++1++

There are far more patients with metastasis to the brain than with primary brain tu-mour. Patients with intracranial metastasis have three therapeutic options:1. Biopsy followed by conventional external radiotherapy2. Surgical removal of the tumour followed by conventional external radio-

therapy3. Stereotactic radiotherapy either as single therapy (1 fraction so-called gamma

or Linac knife surgery) or in several fractions (usually 2 or 3; Linac radio-therapy). The therapeutic options mentioned under this point 3 are not con-sidered surgical and will not be dealt with in this report.

Two randomised trials are included of therapy in cases with a single brain metastasis (104,106) in which resection plus radiotherapy vs. biopsy plus radiotherapy are com-pared. For patients with stable extracranial disease, both trials clearly show the benefit of open surgery plus radiotherapy compared to biopsy only plus radiotherapy in terms of survival as well as quality of life.

37

Vecht et al. (104) reported a series of 63 randomised and evaluable patients of whom 32 were randomised to surgery and 31 to radiotherapy after biopsy only. Median sur-vival for those undergoing surgery was 12 months compared to 7 months for those who were only given radiotherapy. At one year, 50% of the patients in the surgery group were functionally independent as against 17% in the biopsy group, irrespective of type of tumour. Many patients had an improved WHO functional status after treat-ment and kept their WHO status 0 or 1 until they died. Patchell et al. (106) reported a study including 48 patients (25 to surgery plus radiation, 23 to biopsy plus radiation). Median survival in the surgical group was 40 weeks compared to 15 weeks in the biopsy/radiation group. Additionally, there was new tumour growth in the original metastasis site in 20% of the surgical group vs. 52% in the biopsy/radiation group. Measured by median functional independence (KPS>70), the surgical group achieved an interval of 38 weeks compared to 8 weeks for the biopsy/radiation group.

ConclusionPatients highly likely to benefit most from surgery are:1. Those who have one metastasis2. Those with either no or other (extracranial) stable disease3. Controlled cancer, limited to primary tumour4. Expected remaining survival >2 months

Surgery and radiotherapy are superior to biopsy plus radiotherapy in terms of longer median survival as well as functional independence.

4.2.3 Neurologic failure in cases of metastasis to the spine

Symptom Type of cancer

Treatment Reference Evidence level

Deteriorating neurologic function

Various types of primary can-cer

Surgery 185 Young 129 Cappeletto151 Jackson138 Galasko139 Gilbert172 Olerud156 Kluger146 Harrington176 Sundaresan179 Turner173 Jónsson

1+3

33

Eleven publications were included in the final analysis on neurologic functioning. Only one study was prospective and randomised; the others were non-randomised prospective or retrospective series of patients. The publications reaching stage 3 in the evaluation process were independently assessed by orthopaedists and neurosurgeons. There was complete agreement except for one article by Cappeletto et al.(129), which was excluded by the orthopaedists because it included too few patients.

As most patients suffering from intraspinal metastatic tumours die from their primary tumour, the purpose of surgery in these cases is not longer survival per se. Median time of survival for patients with spinal metastasis varies depending on the type of

38

primary tumour and the degree of metastasis. In the study by Turner et al., patients with metastasis had a median survival of only 4.1 months, while patients with more localised metastases had a median survival of 14 months. Comparable survival was also found in the study by Jackson et al. (151) on renal cancer (12.3 months).

Hence, the objectives of treatment of metastatic intraspinal tumours are:1. To reduce pain2. To maintain or regain neurologic functioning

Patients with intraspinal metastatic disease have the following therapeutic options:1. Radiotherapy (RT) only2. Laminectomy (only) + RT (posterior radiation)3. Posterior stabilisation +/- laminectomy + RT4. Anterior access (resection of vertebra) with anterior/posterior/combined stabil-

isation + RTAll these procedures are described in the articles included here.

The only randomised and prospective trial (185) compared laminectomy (without sta-bilisation) plus radiotherapy to radiotherapy alone. The trial is more than 20 years old and rather small, including a total of 29 patients with 16 in the surgical group. Pain-lessness was achieved in about 50% of patients. There was a moderate improvement in neurologic functioning. No significant difference was observed between the two groups in terms of painlessness or improved neurologic functioning. Similar results have been reported by Gilbert in a non-randomised trial including 65 patients treated with laminectomy and radiotherapy compared to 170 patients treated with radiation only.

In three other patient series (129, Jónsson et al., 138) in which posterior stabilisation with or without decompressive laminectomy was used, painlessness was achieved in between 80% and 90% and improved neurologic functioning in 50 to 60% of patients. In Jónsson’s study (173), 19 out of 25 immobilised patients regained their ability to walk.

ConclusionBecause of better diagnostic methods (CT, MRI), improved or simplified surgical techniques and better oncologic therapy there is now a more active attitude to surgical treatment of spinal metastases.

No randomised prospective studies have been carried out in order to compare some of the surgical methods or to compare surgery to any type of stabilisation without radio-therapy only. All patient series reported here (9 of which have been assessed by us) showed very good palliative effect in all patients, irrespective of surgical method. Laminectomy combined with radiotherapy but without stabilisation was no better than radiotherapy only in terms of palliation or of improved neurologic status and cannot be recommended. Surgery with anterior access with decompression and stabilisation is usually used for cervical metastases in which pain is the dominating symptom in most patients. The limited posterior surgical access with a pedicle screw stabilisation, with or without laminectomy, seems to be the most promising type of primary surgery for the majority of patients (173) with thoracic or lumbal metastases. More extensive forms of surgery in such conditions (for instance, with anterior access) should be con-

39

sidered a secondary procedure limited to patients with metastatic disease who are still in good physical condition and have a life expectancy of more than 12 months.

Radiotherapy should not be given preoperatively because of the increased risk of sur-gical complications, but should be given postoperatively.

Patients with paraplegia or severe paraparesis showed little or no neurologic improve-ment after surgery. This underscores the importance of an early diagnosis, speedy transfer to a hospital that offers this treatment and immediate surgery if severe neurologic failure has been of short duration (less than 12 hours).

4.3Orthopaedic surgery

4.3.1 Surgical treatment of bone metastases

IntroductionIn 2000, a total of 22 185 persons developed cancer in Norway1, 11 434 men and 10 751 women. Breast cancer is the most prevalent cancer in women, constituting 23% of all cancers in women. Prostate cancer is the most prevalent cancer in men, ac-counting for 13.7% of all cancers and 26% of all cancers in men. Cancers in the di-gestive organs account for 23% of all cases in men as well as women. Bone meta-stases are a sign of spread of the disease but not necessarily a sign of terminal disease. In the largest groups of cancers, median survival after such metastases is several years. Bone metastases most often originate in breast or prostate cancers.

Not all patients with bone metastases develop pain that require treatment. Karolinska Institutet in Stockholm has developed a special therapeutic programme for bone meta-stases to which patients may be referred. The experience from this group shows that the risk of a breast cancer patient developing metastases that require treatment could be 10 to 15%; 20% of these patients undergo surgery, either because of a fracture caused by disease in an extremity or because of metastasis to the spine with neurolo-gic complications (322). The others receive radiotherapy or medical palliation.

Our review covers 277 articles, but very few prospective studies and only one pro-spective randomised study (185). The most important work relevant to the situation in Norway has been published by the Stockholm group (183,322). Among the other art-icles, many are quite old, possibly because it has been difficult to publish retrospect-ive studies during the last few years. Several articles are about patients with various forms of primary cancer and in different stages of their disease.

Assessing surgical treatment we have emphasised indications, methods and results. Endpoints have been failure of the surgical reconstruction, time to failure, and rate of infection. The functional level is expressed as proportion of patients with self-as-sessed free use of their arms and the proportion of ambulatory patients, with or without aids. Most of the articles have a follow-up period of more than 24 months for survivors.1 Source: Kreft i Norge 2000, National Cancer Registry.

40

Fracture and/or pain is often an indication for surgical stabilisation. Evaluating pain is difficult, and few studies have been carried out with preoperative pain grading with a visual analogue scale and/or use of analgesics.

The various surgical methods have been assessed according to localisation in bone, use of open or closed technique, cement reinforcement, and complications.

Results have been assessed in terms of complications, protracted pain, function in the extremity (for the back, neurologic function has been assessed), peri- and postoperat-ive (four-week) mortality, and survival. Only a couple of studies have attempted to as-sess improvements in terms of quality of life.

It is not possible to assess palliative surgical treatment of bone metastases without ex-amining the results of the other therapeutic options that exist, hence we have included in our selection of the literature articles on radiotherapy, chemotherapy, hormonal therapy, and bisphosphonates. No therapeutic option has been shown to prolong life (169,170,323).

Radiotherapy has good documented effect on pain in bone metastasis (342). There are also some reports on new bone tissue formation in osteolytic metastasis. It is doubtful whether radiotherapy only can heal the fracture; there is, on the contrary evidence that suggests that radiotherapy interferes with the chondrogenesis that is necessary for the healing of a fracture (150). This provides theoretical support for choosing prophy-lactic stabilisation before radiotherapy.

Surgical treatment of fractures

Table 4.1.Symptom Type of

cancerTreatment Reference Evidence

levelFracture Various types

of primary cancer

Surgery 183 Wedin 134 Dijstra144 Harrington

4 34

Load pain as an indication for prophylactic stabilisation

Various types of primary cancer

Surgery 154 Kerr150 Hipp153 Keene142 Haentjens322 Wedin165 Mirels

34 4 4 4 4

There is broad agreement to the effect that patients with pathologic fractures need sur-gery because the patient’s remaining lifespan is so short that one cannot wait for the healing of a fracture before the extremity can be used; hence there is also broad agree-ment on the choice of an osteosynthesis or a reconstruction that is so strong that it al-lows an immediate load and lasts throughout the patient’s remaining lifespan.

We have included two patient series (134,154) in the basis of evidence, but also used review articles in order to describe the issue (table 4.1). Four-week perioperative mor-tality of 0 to 18% has been reported in 26 articles. The three largest studies including

41

a total of 846 patients cite, respectively, 8%, 15% and 18% mortality (134,144, 183). 23 articles allowed estimates of postoperative infection rates; 0–12% is reported. The two biggest, including a total of 613 patients, both report 5% infections.

In this report an attempt has been made to assess the results according to localisation and type of primary cancer disease.

Most studies report results in several types of cancers. Breast cancer is the major type, with from 70% to 80% of included patients, followed by prostate cancer. There are some studies that only assess results with breast cancer and renal cancer with bone metastases that require surgery (124,125,153,155).

Prophylactic stabilisation of facturesThere is substantial disagreement on the indications for prophylactic stabilisation. There are three major objections. By far the largest numbers of metastatic patients re-ceive sufficient palliation without surgery, even with extensive destruction of bone tissue. Adequate stabilisation has relatively high mortality (154) and causes in itself reduced mobility over a long period relative to the remaining lifetime. There are no reliable methods at hand for assessing the remaining bone’s resistance to fracture. The best method is probably CT, taken together with recordings of several phantoms /skje-lettfantomer, QQQ/ with known maximum load in relation to bone density (150). This illustrates that the strength of the remaining bone and the size of the bone are of greater importance than the amount of destroyed bone tissue.

By far the most of the studies that have been carried out are based on femoral destruc-tion. The most important criterion is the pain caused by load, followed by whether or not the lesion is in the proximal part of the femur. Dislocation [QQQ; avløsning av] of the lesser trochanter/destruction of calcar is an auxiliary indication. Most pathologic fractures happen in lytic metastases. Several authors also report that destructions above 2.5 cm and/or above 50% of the circumference give increased risk of fracture. It is, however, hard to assess this and no criteria have been validated in major studies (125,142,153,165).

It is difficult to recommend prophylactic surgery on the basis of the documentation we have identified. A weighted scoring system has been proposed for the assessment of when prophylactic surgery should be carried out (165). It has been evaluated, but few references are made to it in the literature.

The sensitivity to radiation of the metastasis is of importance to the order in which stabilisation and radiotherapy should be carried out when the criteria mentioned are met. Moreover, most authors recommend an individual approach to the decision for each patient, underscoring the importance of close contact between doctors that attend to cancer patients and the orthopaedists who carry out the prophylactic stabilisation. Patients also have differing requirements as to autonomy and physical ability in the fi-nal stage of life. The biology of the primary tumour, the speed with which the meta-stasis grows, and the patient’s remaining lifespan are just as important as the status re-corded by x-rays (165).

42

4.3.2 Pain or fracture caused by metastases to the humerus Table 4.2.

Symptom Type of cancer

Treatment Reference Evidence level

Pain, fracture Various types of primary can-cer

Surgery 142 Haentjens134 Dijstra160 Lancaster

4 3 3

There are only a few studies on treatment of metastasis in the upper arm; we have not included any of them in our pool of evidence. The issue is described in one included and two excluded articles (table 4.2). Most authors recommend primary radiotherapy and surgery if the pain requires this or a fracture occurs; no evidence is cited as to what should be the method of choice. The methods mentioned are marrow nailing with or without cement reinforcement, plates with or without cement reinforcement and prosthesis (134,142,160). The marrow nails described in the relevant studies are not of the contemporary types. It could be that a modern marrow nail provides suffi-cient stability in order to provide palliation. It seems doubtful whether orthosis ther-apy is sufficient for patients with pathologic fractures in the upper arm.

4.3.3 Pain or fracture caused by metastases to the femur Table 4.3

Symptom Type of cancer

QQQ Treatment Reference Evidence level

Pain, fracture Various types of primary can-cer

Collum/caput Surgery 134 Dijstra149 Helwig

33

Trochanteric and subtrochanteric part

Surgery 141 Haber-mann183 Wedin

3

3Shaft of femor (diaphyseal part)

Surgery 131 Colyer132 Coran140 Graupe135 Douglass154 Kerr157 Korkala158 Krawzak159 Kurock184 Yazawa 144 Harring-ton

3333333333

Distal part Surgery 141 Haber-mann183 Wedin

3

3

By far the greater number of fractures occurring when the patients is not in the ter-minal stage require surgery. The choice of method depends of the localisation of the metastasis. Most article report that after reconstruction, 80 to 90% of patients were ambulatory with little pain in the remaining years of their lives unless the reconstruc-tion broke down; hence a lasting reconstruction is the most important criterion of suc-cess. The selected literature is based on patient series (table 4.3).

43

In many patients with deconstruction and pain, radiotherapy will be the first choice. The literature does not support prophylactic reconstruction, though sound judgment indicates that patients with pain that cannot be alleviated and who have reduced walk-ing capacity should undergo surgery. Bone destruction involving the neck of femur (with affection of the greater trochanter or medial cortex in the head of femur) strengthens the indication for surgery.

Neck of femur, head of femur13 articles describe experience with 523 patients in whom standard prosthesis was used after resection of neck/head of femur localised metastasis. This reconstruction failed in 0–10% of patients, though most articles report 2–3% failure. The main reason is a loose prosthesis. Two articles describe failure in 30% and 100% of patients undergoing surgery with osteosynthesis and cement (134,149).

ConclusionIn pathological fractures of the head of femur there is a choice between osteosynthesis reinforced by cement, resection only without reconstruction (Girdlestone), or recon-struction with endoprosthesis. Osteosynthesis only is a poor solution; sufficient stabil-ity is not achieved and redislocation often occurs, especially in destruction of the cal-car. Resection of the head of femur without reconstruction gives good palliation in pre-fracture non-ambulatory patients with severe pain. Most patients with neck of femur fracture are suitable for resection of the head of femur and endoprosthesis re-placement. If the pelvis is not destructed, a hemiprosthesis is used that is cemented into the femur, preferably with a long shaft.

In cases of concurrent destruction of the pelvis, a total hip prosthesis is made with re-inforcement of the pelvis. As with facture in the upper part of the humerus, severe de-struction might necessitate special prostheses.

Upper part of the femurFour articles including 180 patients report experience with plate osteosynthesis re-inforced by cement, with failure in 10%, 40%, 55% and 100%, respectively. One study of a few patients without cement reported 100% failure; another, including 47 patients, had no failures with the use of a reconstruction nail (γ-nail) in sub-trochanteric localisation (141). This study dealt with γ-nail with or without cement. Twelve-month survival was highest in the cement-reinforced group, 51% as against 39%, though it is not clear whether the groups were otherwise similar. The difference in survival was interpreted as related to the degree of stability and hence to degree of mobility for the patient.

ConclusionFractures in this region make for the biggest problems of reconstruction. All methods have a greater tendency to fail than endoprostheses in the neck/head of femur region. The literature provides support for selecting endoprosthesis as well as intramedullary nailing of the so-called reconstruction type with a screw to the head of femur. Endo-prostheses probably pose the least risk of reoperation if there is no need to remove all of the trochanter. By resection of major parts of the trochanter, a resection prosthesis will often (in 20% of cases) become loose. The procedure is time-consuming and must be assumed to give a high rate of complications in this group of patients. A re-

44

construction nail /med sperring QQQ/ is a smaller procedure, and there is a basis for preferring this to plate osteosynthesis reinforced by cement.

Shaft of femurThree articles including 35 patients describe the experience of plate osteosynthesis re-inforced by cement with, respectively, 3%, 28% and 50% failure. Seven articles in-cluding 113 patients describe closed intramedullary nailing without cement with 0% to 8% failure. Three articles with 81 patients report intramedullary nailing procedure /sperremargnagling QQQ/ reinforced by cement, of which no-one failed during the patients’ lifetime.

ConclusionClosed intramedullary nailing with blocking proximally and distally usually immedi-ately gives a load-stable fracture. Cement does not seem to be necessary. Reconstruc-tion nails, thicker than ordinarily intermedullary nails, are recommended. They are made from titan, which means that complications with nail breaks are avoided if the fracture does not heal. In prophylactic intermedullary nailing and use of long-stem femur prosthesis, sudden and fatal hypotension /blodtrykksfall QQQ/ has been repor-ted. This may be caused by bone marrow and tumour tissue being pressed out in the circulation. This risk is probably reduced by first scraping out the metastasis and/or making an opening in the medullary cavity in the distal metaphysis. As far as we have found, there is no evidence indicating that the drilling into the medulla increases the risk of spread of tumour cells in the medullary cavity with ensuing new metastases. It is, however, reported that the medullary drilling can result in spread of thrombi to the lungs, possibly also of tumour cells. The distal part of the femurTwo articles with a total of 57 patients report specifically on this localisation (141, 183) and cite failure frequencies of 8% and 10% with various forms of osteosynthesis and cement reinforcement. Others relate their experience without citing data.

ConclusionThese metastases are treated with scraping, always bone cementing; as osteosynthesis there is a choice between / vinkelplate, glideskrue QQQ/ or retrograde /marrow nail QQQ/. There are no data that provide a basis for preferring any of these; there is, however, less experience with retrograde nailing.

4.3.4 Pain or fracture caused by metastases to the pelvis

Table 4.4Symptom Type of

cancerTreatment Reference Evidence

levelPain Various

types of primary can-cer

Surgery 145 Harrington163 Marco181 Vena

333

Metastases to the pelvic bone are highly usual. Radiotherapy will nearly always be tried before surgery; it is unusual that surgery is necessary. When the destruction has

45

progressed that far, the general condition of the patient is most often assessed as being too bad for him or her to tolerate the big procedures that are necessary for palliative stabilisation. The principle is that if the destruction involves the pelvis, cement with metal reinforcement and possibly prosthesis is used.

There are three articles (table 4.4) with a total of 130 patients that to some extent com-pare three methods of reconstruction. These three methods are standard prosthesis only, reinforcement with an acetabular ring (e.g. Burke-Schneider), and reinforcement with 6 mm thick Steinmann pins (145,163,181). For prosthesis, a 20% failure rate is reported, 10–15% after about 4 months with an acetabular ring, and 0% and 10% after about 12 months for acetabular ring. A couple of articles also describe the so-called saddle prosthesis.

ConclusionPathologic pelvis fractures (acetabular fractures) could give extremely strong pain from the pelvis and loss of ambulatory function. If the destruction is so big and the re-maining lifespan so long (more than three months) that surgery must be carried out, scraping and cementing with pin reinforcement is probable the most durable solution.

4.3.5 Pain or fracture caused by metastases to the spine

Table 4.5Symptom Type of

cancerTreatment Reference Evidence level

Pain, fracture. Prophylactic stabilisation

Various types of primary can-cer

Surgery 185 Young139 Gilbert 172 Olerud138 Galasko156 Kluger146 Harrington176 Sundaresan179 Turner173 Jónsson151 Jackson155 King174 Rompe182 Venbrocks

1+33333333

Bone metastases are frequently to the spine and proximal parts of the long bones. The true incidence of bone metastases from all forms of cancer requiring treatment is un-known. If one assumes that metastases from other cancers give the same need of treat-ment as metastases from breast cancer, in Norway about 1000 patient will be in need of treatment and about 150 undergo surgery. About 5% of patients with metastasis to the spine will be in need of surgery because of neurologic complications.

In 70% of cases, the metastases are localised to the thoracic region, 20% to the lumbar region, and 10% to the cervical region. In most cases the corpus of the spine is at-tacked; isolated metastases to the intervertebral joints or the spinous process of ver-tebra rarely occur (171).

46

One single article reports that patients with lumbal metastases had a median survival of eight months (172). Remaining lifespan is best related to the time from the discov-ery of the primary tumour up until the time when the spinal metastasis gave symp-toms: 15 % of the metastases have onsets without known primary focus.

Most studies date back a number of years (table 4.5). In many, radiotherapy is re-commended as the first choice (138,185). It is, however, a big problem that patients who develop neurologic /utfall QQQ/ could quickly become paraplegic; quite natur-ally this will have big consequences for their functioning during their remaining lifespan. Still there is no basis for treating these patients prophylactically.

As mentioned, radiation is the first treatment of choice, but in cases of osteolytic metastasis with fracture and instability, radiation probably is of little effect (138,156). These patients should therefore be evaluated for surgical relief and stabilisation. Re-commendations include standard x-ray examination, CT of the relevant region, and MRI of the total column before surgery. Remaining-lifespan prognosis will be a con-tributing factor for whether or not one decides on surgery. A scoring system has been developed for preoperative evaluation of remaining lifespan for patients with spinal metastases (178), but has not been validated.

Patients with spinal metastases should definitely be operated on before they develop large neurologic QQQ /utfall/. Patients with quick onset of total paralysis have a bad prognosis for improved neurology, irrespective of treatment. In cases of minor neuro-logic /utfall QQQ/ and slower onset, 80% will improve and 50% regain good ambulat-ory functioning with surgical relief and stabilisation (139,146,156, 176).

Earlier, only laminectomy was commonly used. This might increase instability and hence the pain and is no longer recommended as the only procedure. The only pro-spective randomised trial we have found is done between laminectomy only and lam-inectomy with radiation added. This trial showed no reliable difference between these groups but is not relevant now as surgical methods have been improved (185).

It is now discussed more often whether or not one should use anterior or posterior ac-cess to the vertebral corpus on these patients (166,179). Most authors recommend that the back is stabilised. According to the literature, posterior access gives lower morbid-ity and mortality. Cement reinforcement could also be an option for these patients. In patients with metastases from renal cancer, embolisation of the blood vessel to the tu-mour 24 hours preoperatively is recommended. There are, however, conflicting re-ports in the literature on this point too (172,185).

Anterior access requires special surgical skills and is only recommended for patients with a good remaining lifespan prognosis. If the morbidity after anterior access is to be defensible, the remaining lifespan must be one to two years. For patients with spinal metastases, this is not often the case. With anterior access there is 10% four-week perioperative mortality and 12% infections, while the corresponding figures for posterior access are 3–4% and 2–3% (138,156,179). In patients with long expected re-maining lifespan, anterior stabilisation is, however, required in order to prevent failure of the reconstruction. The more recent literature recommends posterior access, pos-sibly with resection of /bue/base QQQ and tumour in corpus, followed by stabilisation (156,173).

47

ConclusionBone metastases that give strong pain should be treated. The first choice is radio-therapy. Surgery is an option for fractures and for those patients in whom radio-therapy has no effect.

Surgery on the extremities may be done in all departments that carry out prosthesis surgery and fracture surgery. The choice of method of surgery on the extremities will depend on localisation and the degree of destruction of tissue because of metastasis.

Spinal surgery requires collaboration with an oncologist, a radiologist and, as the case may be, a neurosurgeon and an orthopaedists and should be carried out in regional hospitals. For spinal surgery, posterior access with relief /avlastning QQQ/ and stabil-isation is often recommended.

The prognosis for survival is severe and the treatment will not prolong life. Although there are no good prospective studies, there is much to indicate that quality of life is considerably enhanced with surgical treatment, provided that there is a good indica-tion.

Today there is a scientific basis for developing good guidelines. The annual need in Norway is estimated at 100 procedures on extremities and 50 spinal procedures.

4.4Thoracic surgery

Three therapeutic areas have been assessed:1. Surgical management of metastases aimed at prolonging survival2. Obstruction of central airways aimed at relief of symptoms3. Stenosis or occlusion of the superior vena cava aimed at palliation.

In addition to conventional surgery, we include laser therapy as well as various forms of blocking and stenting, these being within the scope of work of the surgeon.

It could be said that surgical management of metastases often has a curative aim and hence is beyond the scope of this report. In by far the most cases, however, the aim will be to prolong life and the disease-free /symptom-free? QQQ interval, and we have chosen to consider this intervention as palliative.

A total of 90 articles have been assessed, 37 of which in depth. By far the greater number has been patient series. There are few prospective randomised studies. Eight articles on surgical management of metastases have been included, nine on airways obstructions, and three on stenosis/occlusion of the superior vena cava.

4.4.1 Difficulty breathing and survival in metastasis to the lungs

Symptom Type of cancer

Treatment Reference Evidence level

48

Pain, difficulty breathing, accu-mulation of mu-cus

Various types of primary cancer

Conventional surgery, or laser

196 Mineo186 Billingsley187 Billingsley204 Weiser195 Meyer200 Schirren202 Mead203 van Geel

1++3

3

33333

Several factors are important:

- Type of primary tumour is important. Among the various type of cancer, can-cer of the testis has by far the best results (Schirren); up to 67% five-year sur-vival is reported. The included literature on treatment of metastases from soft tissue sarcomas also shows good results (186,187,202-204). Three-year sur-vival is reported from 54% (two-year, 50%) and five-year survival from 25 to 38%. Weiser (204) reports median survival after resection of metastases from osteosarcomas of 11 months.

- The disease-free interval from the treatment of primary tumour up until meta-stases occur is of importance; the longer the interval, the better the results. There is disagreement as to what the limit is, but from 1 to 2.5 years is sugges-ted (186,187,203).

- All authors agree on the importance of all metastases being resectable and on complete resection. In soft tissue sarcoma, Ueda (202) reports that the number is not important, nor is it important whether they are unilateral or bilateral. For osteosarcoma, Weiser (204) reports that increased number and bilateral occur-rence is important for the prognosis.

Conventional surgery is the traditional approach, and still valid. There are, however, a number of reports on resection of metastasis with laser. The advantage is that it pre-serves more parenchyma, hence it can be used in sites where traditional resection would have been impossible (196). It can also be repeated (204); resection of up to 110 metastases in one patient has been reported (202).

4.4.2 Obstruction of the central airways

Symptom Type of cancer

Treatment Reference Evidence level

49

Pain, problems breathing, accu-mulation of mu-cus

Bronchial primary can-cer or local metastasis from adja-cent organs.

Stenting or laser therapy

191Chella192 Diaz-Jimenez188 Bolliger190 Brutinel193 George197 Miyazawa198 Monnier205 Wilson325 Cacalier

1+1+

3333

333

Centrally located bronchial cancer, sometimes also malignant processes in adjacent organs, can choke the airways partially or completely. Symptoms will be coughs, dys-pnoea, haemorrhage, atelectasis and pneumonia; they reduce quality of life and could be life-threatening.

In two randomised studies, laser surgery was compared with either photodynamic therapy (192) or combined with brachytherapy (191). Photodynamic therapy turned out to be just as good as laser therapy, but there were staging differences between the groups that make the results inconclusive. A combined treatment with brachytherapy and laser gave the most prolonged palliation. This is a small study with 15 and 14 in each group and the randomisation is inadequately described.

In a prospective series of 28 patients, 23 (82%) had improved ventilation and per-fusion of the lungs (193). Another prospective study of 116 patients who underwent 176 treatments showed reduced breahing difficulty in 66%, while 41.2% had reduced symptoms of pneumonia. Repeated laser treatment is often necessary; a series of 1839 patients underwent a total of 2610 treatments (223).

Either silicon stents (188) or self-expanding metal stents (197,198,205) have been used. Laser therapy of the process of stenosis, possibly combined with stenting, im-mediately relieves symptoms. Experienced operators have few complications. Natur-ally, the effect is gradually declining as new tumour growth occurs, but then the treat-ment can be repeated Treatment results can be measured objectively by parameters of respiration physiology (FVC, FEV 1 and PF). Clear results are also found through quality of life measurements (Karnofsky Index, WHO Index).

4.4.3 Stenosis/occlusion of the superior vena cava

Symptom Type of cancer

Treatment Reference Evidence level

Plethora, face swelling, strong headache with visual disturb-ances, influence on conscious-ness

Most often local meta-stasis from bronchial cancer

Stenting 194 Marcy199 Shah201 Thony

333

50

More often than not, the reason for the obstruction of the superior vena cava is local metastasis from bronchial carcinomas. This condition gives a vast oedema in the up-per half of the body in which the cerebral symptoms are the most troublesome and, after some time, life-threatening.

Often it is possible to improve the patient’s condition quite quickly through percu-taneous blocking preceded thrombolysis, as the case may be. In most cases this ther-apy should be followed by stenting. Reports of the results from three series of patients with, respectively, 13, 26 and 39 patients tell of immediate and good palliation with a method with few complications (194,199,201). These patients invariably have ad-vanced disease; usually the vein will stay open until the patient dies from his or her cancer. Median survival in these studies is, respectively, 4.8 months, 13.5 weeks and 5.5 months.

ConclusionIn some patient groups, metastasectomy prolongs life. Patients with metastases from soft tissue carcinomas or carcinomas of the testis have the best prognosis.

Obstruction of the central airways caused by cancer could in most cases be treated with good symptomatic effect, though life is not prolonged. Laser and, possibly, stent-ing are the preferred methods.

Stenosis or occlusion of the superior vena cava can be treated with blocking and stent-ing, possibly preceded by thrombolysis. This treatment gives immediate symptomatic relief and is recommended.

4.5Urologic surgery

IntroductionThe urologic types of cancer include prostate cancer, cancer of the bladder, renal can-cer, cancer of the renal pelvis, of the ureter, testis and penis. In 1999 there were 21 200 new cancer cases in Norway, of which 23% (4928) were urologic cancers. In the same year the total number of patients with urologic cancer in the population (pre-valence) was 30 877 (21% of all cancer cases) and 1774 persons died from urologic cancer. The majority of these deaths were caused by prostate cancer (1119) while only 10 patients died from cancer of the testis and 8 from cancer of the penis. In compar-ison, the prevalence of cancer of the testis was 3921, of the penis 288. These mortality figures correspond well to the resources needed for palliative treatment of the various form of urologic cancer. For example, palliation of advanced prostate cancer requires considerable efforts at several levels, in hospital and ambulatory.

We have been tasked with assessing the documented effect of surgical palliation in urologic cancer. Oncologic (radiation) and other palliative therapies have not been in-cluded. On the basis of clinical experience with the need for palliation, supported by statistics, we have chosen to limit our assessment to prostate cancer, cancer of the bladder, and renal cancer. Numerically speaking, cancer of the penis is a very small problem, and the few men who die from advanced disease are only in exceptional cases in need of surgical palliation. For cancer of the testis the need for palliation is small, as by far the most patients are cured. Close to 100% of patients with local or re-

51

gional diseases are cured, and even among those with highly advanced disease about 80% are cured. For those few who die from cancer of the testis, surgical palliation is not a relevant issue.

In addition to local problems from the affected organ, the cancer could cause loco-regional disease which may call for palliation. This may be due to direct ingrowth from the tumour or metastasis to nearby lymph nodes. An important problem in a uro-logic context is a cancer that grows in such a way that it produces malignant obstruc-tion of the ureter followed by uraemia. This may be urologic cancer (of the prostate or bladder) or other types of cancer, most frequently colorectal or gynaecologic cancers. Literature searches have been conducted specifically on this issue; it turned out to be the search that gave most of the relevant hits. Non-urologic symptoms caused by uro-logic cancer disease are considered in the respective chapters (gastrosurgery, neuro-surgery and orthopaedic surgery).

Distant metastasis from other types of cancer to the urogenital organs very rarely oc-curs. Metastases to the kidneys and testicles (most frequently from lymphomas) may occur; they are of small practical importance.

Over the last few decades, urologic surgery has changed a great deal; open surgery and traditional endoscopic surgery in the lower urinary tracts have been replaced by or supplemented by less invasive methods. This applies above all to radiologic proced-ures such as embolisation and various catheter insertions (e.g. internal ureteral stent-ing and percutaneous nephrostomy), hence we have found it relevant to include these semi-invasive techniques in our searches.

After the last stage in the assessment of the articles identified by the searches, 31 art-icles remain in which we are inclined to find that the palliative intent is clearly formu-lated, and which to some extent can illuminate the issue by way of data. The material is certainly varied (from 3 to 118 patients). Articles focusing on techniques only as well as case reports have been excluded. It should also be noted that articles from the 1970s and 1980s are not up to the standards of documentation etc. that are required today.

Only one randomised controlled study was found ( 229) in addition to one case-con-trol study (239). The others were non-prospective patient series, mostly institutionally based.

It may seem as if the final number of articles is low when the issues involved are pre-valent conditions. The reason is probably that some of the therapeutic modes seem so evident that they are in fact not evaluated in these groups of patients, quite apart from the difficulty of conducting studies with patients in the terminal stage of cancer.

EpidemiologyProstate cancerIn 1999, 14 376 patients in Norway lived with a diagnosis of prostate cancer; 1119 persons died from the disease. The incidence increases steadily from the age of fifty, but very few patients are diagnosed before they reach this age. Prostate cancer is char-acterised by a high degree of biological indeterminacy in the individual patient. On the basis of the data in the Norwegian Cancer Registry one might say that cancer ex-

52

clusively in the prostate gland has a five-year relative survival of about 80%, while the corresponding figure in disease with distant metastases is about 20%. Disease that is locally advanced, metastatic or in which radical therapy (radical surgery or radi-ation) has failed, is treated hormonally. Standard hormone therapy is surgical or med-ical castration which eliminates the testicles’ production of testosterone. This therapy is in point of principle palliative and will help about 80% of patients. For patients with distant metastases, average duration of the response will be slightly less than two years before the disease progresses into a so-called hormonally refractive phase and the patient dies after on average six months. The same goes for hormonally treated locally advanced disease, but the time horizon could then be substantially longer than with metastatic disease. It is particularly in this phase, when hormonal therapy has ceased to have effect, that there is a need for various forms of palliation.

Renal cancer In 1999 there were 448 new cases of renal cancer in Norway, 2866 persons living with this diagnosis and 304 dying from this disease. Most die from distant metastases after resection of the kidney with the primary tumour. Only a small minority have not had their primary tumour resected, either because it was impossible to operate or be-cause the disease had several metastases at the time of diagnosis. By and large, pa-tients with an intact primary tumour are candidates for locally oriented urologic palli-ation. A characteristic of renal cancer is that it is highly resistant to radiotherapy as well as chemotherapy.

Cancer of the bladderIn Norway in 1999, there were a total of 8750 patients with cancer of the bladder; 797 new men were diagnosed and 272 women. Age-adjusted incidence in the same year was 21/100 000 among men and 5.5/100 000 among women. The incidence has gone up steadily among men and been relatively stable among women. Cancer of the blad-der strikes down in the elderly part of the population with increasing incidence from the age of forty-five, and reaches a top among people in their seventies; five-year sur-vival is 72% in men and 62% in women. The difference might be explained by the fact that women are diagnosed at a later stage with more severe disease. For localised cancer of the bladder, five-year survival among men is 80%, among women 70%. The corresponding figures for regional disease are 22% among men and 21% among wo-men. Most cases of cancer of the bladder are superficial and rarely develop into loc-ally advanced disease, hence only a minority of patients will have locally advanced disease that requires palliative surgery. The literature on palliative surgery in the con-ditions of haematuria and vesicointestinal fistula has been assessed.

4.5.1 Haematuria

Symptom Type of cancer

Treatment Reference Evidence level

Haematuria Prostate can-cer

TUR No relevant studiesEmbolisation No relevant studies

Renal cancer Nephrectomy No relevant studiesEmbolisation 250 Marx

251 Nurmi33

53

Cancer of the bladder

TUR No relevant studiesLaser No relevant studiesEmbolisation 323 Guillou 3Irrigation 242Brühl

241Arrizabadaga245 Ludgate248 Servadio322 Fair

33333

Prostate cancerMacroscopic haematuria, partly with clot retention (”bladder tamponade”) in patients with advanced prostate cancer is a routine problem in departments of urology; the in-dividual patient may experience this several times daily. The standard treatment is transurethral evacuation of coagula from the bladder, possibly combined with a transurethral resection/revision of the prostate (TURP). In our review of the literature we did not, in fact, find any studies of this approach, the reason probably being that this treatment is so self-evident and so well documented through decades of clinical practice that no-one has found it worth studying. Patients with several such episodes are offered palliative local radiotherapy of the prostate; this is, however, outside the scope of our literature search.

It is also known that selective/super-selective radiologic embolisation of branches to the prostate from the internal iliac artery has been used in patients in whom haemo-stasis by way of TURP or radiation has not succeeded. We have, however, not found any literature with a patient material that documents the effect of this treatment, such as in cancer of the bladder (see below).

Renal cancer Visible bleeding into the renal pelvis from a primary tumour can produce pain in the flanks caused by clot obstruction in the ureter and anaemia requiring transfusion. In earlier years, attempts at nephrectomy used to be an approach, but no patient material on this has been found. There is, however, now widespread agreement to the effect that embolisation of the renal artery is the method of choice in this situation. The method has been described for benign renal tumours, as in angiomyolipoma, but pa-tient materials on treatment of bleeding from renal cancers are scant. Two publica-tions (250,251) do, however, report on this method applied on the indication of mac-roscopic haematuria. Marx et al. (250) treated 13 patients with renal bleedings. In all patients the macroscopic bleeding stopped after embolisation, while 3 patients de-veloped a new bleeding after 1 to 10 months. In a report from Nurmi (251), the mac-roscopic haematuria was stopped in 11 out of 14 patients. Both groups report that most patients have temporary flank pain and fever (1–5 days) and there were, respect-ively, 2 and 1 fatal outcomes in connection with this treatment. It is not clear whether or not these were related to the treatment or were a consequence of advanced disease. Hypertension in patients who used to be normotensive occurs in a small minority of both patient groups.

Cancer of the bladderHaematuria is the most common symptom in renal cancer and is routinely treated with transurethral resection of the bleeding tumour (TURB). We found no publication on this therapeutic modality, probably because it represents a long and appropriate thera-

54

peutic tradition. Patients may, however, develop haematuria from a locally advanced tumour of the bladder that cannot be controlled with TURB.

Rinsing the bladder with various substances in order to stop a bleeding has been de-scribed. Several authors have used continuous rinsing with a 1% aluminium po-tassium sulphate solution. The procedure does not require anaesthesia. Arrizabadaga et al. (241) achieved complete response in 66% (10/13) of the patients, partial re-sponse in 15% and no effect in 20%. The side effects were few (tenesmus/spasm of the bladder) and no cases of aluminium poisoning, shrinking of the bladder, QQQ or vesicoureteral reflux were observed.

Irrigation with formalin (1%–10%) is described in older publications (248,322). It is an efficient method, 7/8 with complete response reported by Servadio and Nissenkorn in 1976 (248), and similarly 14/18 according to Fair in1974 (322). Serious side effects have been reported from the use of formalin 10%, with shrunken bladder /skrump-blære QQQ/, vesicoureteral reflux and ureteral obstruction. The procedure is done in general anaesthesia or epidural anaesthesia, often done when aluminium rinsing is not successful.

Selective obstruction of the internal iliac artery or more peripheral vessels is described in two articles with 7 and 3 patients respectively (223,242). The procedure has been carried out unilaterally as well as bilaterally with “prolonged” symptomatic “good” effect and without “major” side effects. The authors recommend the procedure for strong bleedings that cannot be controlled with TURB or rinsing of the bladder, but the documentation is weak.

Hyperthermic perfusion (45C) of the distended urinary bladder is described as a treat-ment for intractable cases of haematuria in cancer of the bladder (245). The method was effective in all 13 patients but requires epidural anaesthesia and an advanced ir-rigation procedure. There is no report of the method being used in Norway. We have not assessed palliative radiotherapy in haematuria.

4.5.2 Urinary retention

Symptom Type of cancer

Treatment Reference Evidence level

Urinary reten-tion

Cancer of the bladder

Urinary diver-sion

309 Montie 3

Prostate Transurethral resection (TUR)

229 Thomas 246 Mazur

1+3

Stenting 249 Yachia240 Anson

33

Difficulty in voiding the bladder is a very usual problem in prostate cancer. Mazur and Thompson (246) have reviewed the results from ”channel” TURP in 41 patients with prostate cancer, 70% with metastatic disease, the others with locally advanced disease. 22% were patients with urinary retention requiring a catheter; 78% had sub-jective difficulties voiding. All patients were able to void spontaneously after the pro-cedure without additional treatment. Nine patients had to undergo a new TURP after on average 15 months and another 2 patients had to undergo a third TURP. There

55

were no perioperative deaths, but 2 patients became completely incontinent as one de-liberately operated down in the external sphincter because of cancer ingrowth. Two patients who had previously undergone radiotherapy developed stress incontinence. The authors are of the opinion that TURP in advanced prostate cancer gives a some-what higher risk of incontinence than in surgery for benign prostate hypertrophy but that this risk is still acceptable. Caution should be taken if the disease affects the ex-ternal sphincter and the risk of incontinence is also increased following previous local radiotherapy (about 7%).

In a randomised controlled study of 22 patients, Thomas et al. (229) compared TURP plus bilateral orchiectomy and quick postoperative removal of the catheter (group A) with bilateral orchiectomy only and removal of the catheter after 1 month (group B). The two groups were comparable and comprised patients with locally advanced can-cer (stage T3/T4) who had not undergone hormonal therapy. In group A, 5 out of 10 patients immediately had spontaneous voiding after postoperative removal of the cath-eter. Four patients had to have a catheter for 1 month postoperatively and the last pa-tient had to undergo a new TURP after 2 months. In group B, 10 out of 12 patients were voiding spontaneously 1 month postoperatively while 2 patients had to undergo a new TURP after 2 months. There were only small differences in length of hospital-isation, and the number of complications in the TURP group was low (2 blood trans-fusions and 1 urinary tract infection). The authors recommend hormonal therapy fol-lowed by removal of the catheter as the therapy of choice for this group of patients. TURP should be held in reserve for patients unable to void spontaneously after 2 months. The authors do not, however, provide data on how long the therapeutic effect lasted. It should also be noted that surgical castration was carried out in this group of patients, though medical castration with a GnRH agonist is now standard procedure. As the effect of castration occurs a few weeks later with medical castration, one should allow for 2 months with catheter if this therapeutic modality is chosen. Hospit-alisation is, however, eliminated or substantially reduced with medical as opposed to surgical castration.

Two more recent articles (240,249) have looked into the use of temporary prostatic stents (ProstaCoil) placed in the prostatic part of the urethra pending the effect of ini-tiated hormonal therapy, a therapy used for patients with carcinoma of the prostate who still has hormonal therapy in reserve. Anson et al. (240) used this therapy on 10 patients with locally advanced disease with or without distant metastases. The patients were hormonally treated with either antiandrogen (9 patients) or with GnRH agonist (1 patient). Eight out of 10 patients kept their stents for 3 months, as intended. One patient had to have the stent removed after 2 weeks because of local pain from the stent and underwent a TURP; the other patient lost his stent spontaneously after 4 weeks. Yachia and Aridogan (249) used a self-expanding prostate stent in 27 patients with locally advancer prostate cancer and urinary retention combined with hormonal therapy. 24 patients voided spontaneously after insertion of the stent while 3 patients had to be treated for retention of coagula in the bladder. The majority (16) of the pa-tients had their stents removed after 3–6 months; the others somewhat later. After on average 2 years (24.8 months), 15 patients voided satisfactorily assessed on the basis of urine flow and measurements of residual urine (<100 ml). Both groups of authors view stenting of the prostate as a very good alternative to TURP or to transurethral catheter until hormonal therapy has taken effect.

56

4.5.3 Flank pain

Symptom Type of cancer

Treatment Reference Evidence level

Flank pain Renal cancer Nephrectomy 250 Marx251 Nurmi

33

A renal tumour may completely fill out the flank and generate pain because of its volume as well as infiltration in the surrounding structures. Attempts at palliative nephrectomy will usually be hazardous or impossible. The frequency of flank pain re-quiring treatment is not given in the literature, but experience indicates that it is low. Various types of analgesic treatment, from drugs to epidural analgesia, might be con-sidered.

However, two publications from the 1980s report experience with infarction QQQof the kidney by embolisation of the renal artery as a treatment for flank pain from a loc-ally advanced tumour (250,251). This intervention was originally launched about 30 years ago in order to technically ease removal of a kidney with a large tumour and, it was believed, improve survival through unclear immunological mechanisms. These indications have, however, been abandoned. Still, the experience reported in these two articles shows that embolisation could be used in the treatment of flank pain. In a ma-terial of a total of 29 patients with renal cancer who underwent transfemoral catheter embolisation of a kidney, Marx et al. (250) report that 5 patients were treated on the indication of pain; all of them achieved palliation of local pain, though neither the de-gree nor the duration of the pain is stated. Nurmi et al. (251) treated 25 patients in a similar manner, 6 of whom on the indication of pain. Three of them achieved an (un-defined) palliation of severe local pain.

4.5.4 Metabolic disturbances from renal cancer

Symptom Type of cancer

Treatment Reference Evidence level

Symptom

Hyper-calcaemia

Renal cancer Local spread-ing/advanced disease or metastatic can-cer

Nephrectomy 239 Walther 2

Paraneoplastic symptoms

Renal cancer Nephrectomy No relevant studies

Embolisation No relevant studies

It is well known that some renal tumours can produce metabolic/endocrine disturb-ances, either through local spreading or metastatic cancer. One of the reasons for this is probably that these tumours produce peptides that mimic the effect of several hor-mones (including insulin, prednisone, parathyroid hormone, thyroids). Whether this phenomenon is caused by the primary tumour, metastases or both is not clear. Tradi-tionally it has been seen as a possible indication for nephrectomy, even in metastatic disease when nephrectomy is not otherwise indicated. We have, however, identified only one clinical report in which the effect of nephrectomy has been studied. In a

57

case-control study, Walther et al. (239) studied 15 patients with metastatic renal can-cer who had hypercalcaemia and underwent nephrectomy. 18 normocalcaemic pa-tients with metastatic renal cancer and 4 normocalcaemic patients without renal can-cer were used as controls. The authors conclude that cytoreductive surgery (nephrec-tomy) has a temporary effect (<16 weeks) on hypercalcaemia, but that it may enable these patients to undergo immunotherapy, which otherwise would have been difficult.

4.5.5 Vesicovaginal/intestinal fistula

Symptom Type of cancer

Treatment Reference Evidence level

Vesicovaginal/ intestinal fistula

Cancer of the bladder

Cystectomy No relevant studies

Exenteration 257 Olsson 3

A vesicointestinal fistula or a vesicovaginal fistula based on a locally advanced cancer of the bladder is a rare sequela that is highly disabling, with considerable reduction of quality of life. There are hardly any studies of this condition. Olsson et al. 1976 (233) recommend pelvic exenteration on a liberal indication, even in patients with incurable disease; 5 out of 8 patients who underwent surgery and later died, lived at least 10 months without local symptoms.

4.5.6 Malignant ureter obstruction

Symptom Type of cancer

Treatment Reference Evidence level

Ureteral ob-struction

Other types of cancer

Urinary diversion 232 Sharer224 Meyer235 Meyer

333

Percutaneous nephrostomy

234 Emmert228 Janetchek 230 Fukuoka225 Kearney

3333

Percutaneous nephrostomy and/or ureteral stenting

237 Shekarriz 243 Gasparino 244 Harrington 227 Amadzadeh238 Wawrochek

33333

Ureteroneo-cystomy QQQ

No relevant studies

Exenteration 233 Olsson 3Ureteral stenting 226 Casparini

231 Hepperlen247 Minhas

333

Various types of cancer can lead to ureteral obstruction caused by local spreading or metastatic cancer. The obstruction may occur with metastases to the retroperitoneum, mainly in breast cancer, lymphoma or sarcoma, or in locally advanced tumours or lymph node metastases from cancer of the bladder, prostate cancer, gynaecologic can-cer or colorectal cancer.

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This condition is not rare and untreated bilateral ureter obstruction leads to renal fail-ure. Unilateral obstruction could cause pain and infections. Today, the obstruction may be relieved with simple techniques as opposed to earlier approaches with open surgical techniques such as nephrostomy and cutaneous ureterostomy. Deciding whether a patient with locally advanced or metastatic disease could be treated for ureteral obstruction can be difficult. There are several different contemporary methods for resolving ureteral obstruction; nephrostomy (percutaneous or open) ureteral stent-ing (internal JJ stent, extra-anatomic or metal stent), cutaneous ureterostomy, ureteroneocystostomy /finnes ikke på Medline QQQ/. In our review of the literature we have assessed these indications of effect: time outside institution, length of re-maining life, and complications.

The articles often report on patient groups with various forms for cancer, hence it is difficult to come up with specific therapeutic recommendations for the various forms of cancer at different stages. A general recommendation is to show caution in recom-mending relief to patients with general metastatic disease. Several authors (234,235, 243,244) limit the treatment to three groups of patients: Those who have not yet been given oncologic treatment or have been given insuf-

ficient treatment Patients who have been given radiation When it is unclear whether or not there is recidivation and to patients in good gen-

eral condition

The authors report that 41–77% could leave the hospital after relief (224,230,235, 237,243,244). These patients spent from 62% (230) to 86% (243) of their remaining lifespan outside hospital. In one study (231), the proportion of patients who spent their remaining lifespan in hospital was 4.6% of patients with regional metastases and 11.1% with metastatic disease. Only one study (237) gives Karnofsky Performance Score for patients treated with a JJ stent or nephrostomy. Median score is 2 (confined to their beds at home, with pain in spite of analgesics).

How long the patients lived after palliation is highly variable and the reports state this in different ways. Average survival is given as 5–19 months (234,237,243). Others re-port that, respectively 33.3 % (235) and 40.5 % (244) survived 6 months.

The various procedures reverse to a great extent the renal failure in 73–82% (235,243, 244). In Norway today, one prefers to use percutaneous technique or JJ stent inserted retrograde or antegrade. The studies show failure in up to 61% of cases (243) with in-serting a JJ stent because of strictures that one cannot perforate. Percutaneous neph-rostomy thus has a higher success rate but there are complications such as infections, sepsis, leaks and dislocation. With JJ stenting there are complication such as obstruc-tion, infections and sepsis. Reference 326 cites 63% fewer complications and 5.4% serious complications. No study specifies the effect on palliation in terms of pain and infection.

For the other relief methods there have so far not been documented advantages in re-lation to JJ stenting or nephrostomy, but they may be alternatives when these fail.

Conclusion

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There are practically no randomised studies; still there are results from retrospective patient series that provide a reasonably good support for clinical work on palliation of symptoms from advanced urologic cancers.

Haemorrhage from the lower urinary tracts in prostate cancer and cancer of the blad-der is primarily treated with transurethral evacuation of blood from the bladder and, if needed, resection of bleeding cancer tissue, although this therapeutic modality is not described for this indication. In case of repeated bleedings, radiotherapy is recommen-ded. If these modalities are not successful in bleeding cancer of the bladder, bladder rinsing with aluminium potassium sulphate may be used. Alternatively, rinsing with formalin may be tried, but this approach has potentially more serious side effects. Em-bolisation of veins to the bladder is also described, but the documentation of effect is as yet weak. Still it is an alternative if all the modalities described above fail.

Bleeding from a kidney with a cancer in cases in which the kidney has not been resec-ted, either because it is inoperable or the patient has several metastases, is effectively treated with embolisation of the blood supply to the kidney.

Urinary retention in prostate cancer is effectively treated with TURP. The frequency of complications is low, but patients who have received radiotherapy to the prostate/bladder have a somewhat higher risk of postoperative incontinence. If the prostate cancer grows down in the external sphincter, the risk of incontinence is so high that one should maintain an attitude of reserve towards TURP.

In prostate cancer patients with urinary retention who have hormonal therapy as a re-serve option, hormonal therapy plus catheterisation in 1 to 2 months may be preferred to hormonal therapy plus primary TURP (randomised study). Temporary stenting of the urethra pending effect of hormonal therapy is documented as an alternative to TURP.

Flank pain in renal cancer may be relieved through radiologic embolisation of the kid-ney, although the documentation is somewhat scant.

Results of surgical treatment of a cancer-induced fistula between bladder and vagina or between bladder and intestine are not sufficiently documented.

Modern treatment of malignant ureteral obstruction with percutaneous nephrostomy and JJ stenting is relatively well documented. The majority of patients no longer have renal failure and may spend most of their remaining lifespan outside hospital. The main problem with this condition is the selection of patients. Material emphasis in de-termining the indication should be placed on patients’ general condition and life ex-pectancy.

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5 Relevant assessment criteria

5.1Economic aspects of palliative cancer surgery

The pubic health services have several and to some extent contradictory objectives. A committee set up to assess health care priorities in Norway and headed by a former president of the University of Oslo, Inge Lønning, which received broad support in the Norwegian parliament, laid down that effectiveness, severity and cost-effective-ness should be the fundamental criteria for setting priorities in the health services.

Quite clearly, palliative cancer surgery fills the criterion of severity. It comprises a great variety of procedures with varying evidence levels. As the effect of several palli-ative surgical procedures is not documented through randomised controlled trials, it is difficult to give a comprehensive assessment of whether or not the criterion of effect-iveness is filled. Few studies are available on the cost-benefit relationship of palliative surgery; i.e. that the estimated costs of surgery stand in a reasonable relationship to its effectiveness.

We did not search specifically for literature on the costs of palliative cancer surgery, as our terms of reference did not include conducting a comprehensive cost-benefit analysis. We did, however, identify two articles on gastroenterologic surgery for icterus caused by pancreatic cancer which compared costs related to type of stent and surgery. In a randomised controlled study (39), three groups of patients were com-pared: 1 group in which a plastic stent is inserted and replaced when needed; one group with plastic stent and planned replacement every three months and one group with primary insertion of a self-expending metal stent.

Procedure-related morbidity and mortality as well as median survival were the same in these groups. Time to symptoms of stent dysfunction was significantly longer with planned replacement of the stent compared to replacement of the stent when needed. In a cost-benefit analysis with questionable transferability to Norwegian conditions, it was found that costs were lower with primary plastic stents when expected patient survival was less than 3 months, without this having a negative effect on the fre-quency of symptoms of recidivation. The cost estimates were the same for the three therapeutic strategies given an expected patient survival of less than 3 months, without this having a negative influence on the frequency of symptoms of recidiva-tion. The cost estimates were also the same for the 3 strategies with a survival of 3–6 months; metal stents gave lower cost with survival of more than 6 months.

A retrospective study from the Mayo Clinic compared surgical bypass with stenting (40) in patients who had inoperable pancreatic cancer. There were no significant dif-ferences in survival, procedure-related morbidity, or mortality. The costs of bypass surgery were significantly higher than with stenting, also when the costs of stent re-placement were taken into account. Again, the transferability to Norwegian conditions is uncertain.

All treatment requires resources and there are always alternative uses for these re-sources. Resources used for the treatment of one patient will necessary be at the ex-

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pense of another – usually anonymous – patient. This is the argument for cost-benefit being a criterion when priorities are set. The logical consequence is that the health ser-vices should not commit resources to treatment with no effect or negative effect.

Lack of documentation of treatment is no proof that the treatment is without effect. Hence, when there is a paucity of documentation of effect for some form of palliative surgery, it does not mean that the type of surgery in question should be given low pri-ority. The effectiveness of a considerable proportion of diagnostics and therapy in modern health services is still not documented. Considering that one knows little about the effect of palliative cancer surgery (and hence about its cost-efficiency), but that a patient’s condition is very severe, it seems reasonable to assign less importance to the criterion of cost-effectiveness when deciding on the priority of this type of treatment.

5.2 Palliative cancer surgery in Norwegian hospitals

The objective is to use register data in order to have some indication of the scope of and in palliative cancer surgery over the period 1999–2002 and changes that may have taken place over this period.

Information about Norwegian practice is based on data from the Norwegian Patient Registry (NPR) and developed in collaboration with the Patient Classification and Funding (PaFi) Unit, both at SINTEF Unimed. The data basis is all hospitalisations in approved public hospitals and private institutions over the 1999–2002 period. For-eigners who are not resident in Norway have been excluded. The results are sub-divided by region of residence; these are comparable over the period. The datasets start with 1999, chosen because of the introduction of ICD-10.

During the period, the number of hospitalisations with surgery exceeded 300 000 a year, with cancer surgery accounting for 8.2–8.4%. It should be noted that the number of cancer procedures includes major as well as minor procedures in hospital, for in-stance conisation in malignant disease. Cancer surgery here includes all ICD-10 codes starting with a C and codes for preinvasive tumours (carcinoma in situ) D00–D09.

Table 5.2.1 Cancer surgery in Norway as a proportion of total surgery

NORWEGIAN TOTAL 1999 2000 2001 2002No. of hospitalisations, all surgery 299 900 306 992 329 239 345 841No. of hospitalisations, cancer surgery 24 901 25 721 26 952 28 707Cancer surgery as a proportion of all surgery 8.3% 8.4% 8.2% 8.3%

Total numbers are broken down by region of residence so that table 5.2.2 shows total number of procedures, table 5.2.3 number of cancer procedures, and table 5.2.4 cancer procedures as a proportion of all surgically procedures. This proportion varies among regions; residential region North has increased its proportion (6.7% to 7.6%), it is re-duced in the South region (8.6% to 8.2%), East is stable, West and Middle Norway somewhat varying. The lowest proportion is shown for the North region in 1999 (6.7%), the highest for the West region in 2000 (8.9%).

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Table 5.2.2 No. of hospitalisation, all surgery, by region of residence

 No. of hospitalisations for

surgery, totalHealth region (region of residence) 1999 2000 2001 2002East 105 856 106 792 115 951 121 854South 60 454 63 474 67 669 72 440West 56 346 57 776 61 797 63 466Middle Norway 43 760 44 093 46 427 48 638North 33 484 34 857 37 395 39 443Total 299 900 306 992 329 239 345 841

Table 5.2.3 No. of hospitalisation, cancer surgery, by region of residence

 No. of hospitalisations for

cancer surgeryHealth region (region of residence) 1999 2000 2001 2002East 8 983 9 144 9 755 10 193South 5 220 5 317 5 513 5 941West 4 814 5 156 5 344 5 523Middle Norway 3 642 3 694 3 715 4 047North 2 242 2 410 2 625 3 003Total 24 901 25 721 26 952 28 707

Table 5.2.4 Cancer surgery as a proportion of all hospitalisations for sur-gery by region of residence  Cancer surgery, proportionHealth region (region of residence) 1999 2000 2001 2002East 8.5 % 8.6 % 8.4 % 8.4 %South 8.6 % 8.4 % 8.1 % 8.2 %West 8.5 % 8.9 % 8.6 % 8.7 %Middle Norway 8.3 % 8.4 % 8.0 % 8.3 %North 6.7 % 6.9 % 7.0 % 7.6 %

Population rates for the regions are given in table 5.2.5; they show an increase for all regions over the period, with the biggest increase in the North region, from 1.9% to 2.6%.

Table 5.2.5 Hospitalisations per year for cancer surgery per unit of popu-lation by region of residence   Cancer surgery, no. by yearPopulation by health region (region of res-idence* 1999 2000 2001 2002East (average 1 610 054) 2.3% 2.3% 2.4% 2.5%South (average 880 452) 2.4% 2.4% 2.5% 2.7%West (average 924 502) 2.1% 2.3% 2.3% 2.4%Middle Norway (average 636 699) 2.3% 2.3% 2.3% 2.5%North (average 463 526) 1.9% 2.1% 2.3% 2.6%*Population numbers are averages for the years 1999–2002. The proportions of populations are com-puted on the basis of the annual population figures. Source: Statistics Norway.

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Whether the surgical treatment had a curative or palliative intention is not registered, hence it has been difficult to extract completely relevant data. It has, however, been generated a survey of hospitalisations registered with surgery for metastases, though this gives an incomplete picture of the total of relevant palliative surgery.

A sample has been drawn based on diagnostic codes (ICD-10) and procedural codes (NCSP) (see appendix 12.2). Metastasis is used as the main indicator of palliative treatment, hence any curative treatment of metastasis is included in these figures. Metastasis could be the main or sub-diagnosis (table 5.2.6).

Table 5.2.6. Hospitalisations for surgery on patients with metastases in gastroen-terologic, orthopedic, neurologic, thoracic and urologic cancer in NorwaySample of patients 1999 2000 2001 2002Surgery on patients with bone meta-stases– Of this, spinal surgery

330

102

302

122

552

120

418

131Surgery on patients with pulmonary metastasis

247 355 420 521

Surgery on patients with metastasis in the urinary tracts

10 14 41 24

Surgery on patients with cerebral metastasis

167 231 211 238

Surgery on patients with metastasis in the alimentary tract

2515 2737 2751 2829

SummaryCancer surgery as a proportion of all surgery 1999–2002 averages 8.3%, a relatively stable level considering the population increase. Annually, more than 2% of the popu-lation undergo such surgery. There are variations between regions and over the period; in two regions the proportion increased, in one it fell, and in two the propor-tion varies from year to year. The population rates show an increase in all regions over the period in question.

Surgery in cases of metastasis has increased substantially.

5.3Ethical aspects of palliative surgery for cancer patientsPalliative surgery means surgery in which the objective is not curative, but prolonging life and alleviating symptoms (327). The aim is to help persons who are in a very dif-ficult situation (with incurable diseases) in the best possible manner, by a) trying to prolong his or her life, b) alleviating the patient’s symptoms, and c) preventing symp-toms. This objective substantially corresponds to the general objectives of the health services, for example as they are expressed in the Code of Ethics of the Norwegian Medical Association, article 1: “A doctor shall protect human health. A doctor shall cure, alleviate and console.” Still there are some aspects of palliative surgery in the treatment of cancer that are morally challenging; in the following these are tied in with crucial aspects of medical ethics.

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5.3.1 The duty to helpThe duty to help has a strong standing in modern medicine; in many ways it is the de-ontological (the theory about moral duty) core in all health related disciplines. The corresponding duty to attend to and care for the weak has a very long tradition. The same goes for the duty to learn. All these duties are relevant to palliative surgery.

In medicine, the duty to help has been challenged by serious examples of over-treat-ment. Surgeons have been accused of being more ready to take action than their knowledge basis justifies and of having too much professional autonomy. In the days when one removed the colon in order to cure epilepsy, removed the adrenal glands be-cause of hypertension and pinched off the internal thoracic artery in order to treat angina pectoris (328), it was surely based in a desire to help. With the benefit of hind-sight such examples stand out as manifestations of over-treatment, paternalism and hubris rather than of the duty to help.

The duty to help may a) be understood in too absolutist terms, b) be misinterpreted, or c) not counterbalanced by other considerations. There is a danger of this in relation to palliative surgery in which the patient is weak, vulnerable and in great pain, the know-ledge basis on effectiveness and risks is limited, and the patient expects that “everything that is possible” is done.

This means that palliative surgery is an area in which the duty to help has to be ap-proached with a great degree of caution and with reference to the duty to obtain bene-fits and balance benefits against risks, in normative ethics usually referred to as “be-nevolence” and be weighed up against the non nocere duty (330).

5.3.2 Compassion and vulnerability

Facing a patient suffering from cancer, with considerably reduced level of function-ing, and strong pain invokes pity and compassion, which are among the core virtues of medicine (332,333). Selfless help to those who are weak and vulnerable is a tradi-tion of long standing and seems particularly relevant in relation to cancer patients with strongly crippling and painful symptoms.

Pity and compassion may be seen as tied in with the helper’s moral sensitivity and good intentions; these virtues are, however, necessary but not sufficient conditions. Compassion also implies an awareness of whether compassionate acts really help the person that one wishes to help. Benevolence as an ideal requires that one does not act blindly. Drastic interventions with lack of knowledge cannot be justified by reference to the interventions being based on pity and compassion.

5.3.3 Risk and lack of knowledge

There is limited knowledge about palliative surgery; this applies to effects as well as risks. There are very few studies of acceptable quality; moreover, there seems to be considerable variations from hospital to hospital in the treatment of the same condi-tion. Knowledge about preventive palliative surgery is particularly scant (chapter 7). This lack of knowledge about effects, risks and degree of prevention seems morally

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relevant. Professor Alan G. Johnson of the University of Sheffield Surgical Unit ex-presses this in this way:

Many operations for cancer have not been properly evaluated by randomized controlled trials, and there are situations where the placebo effect is likely to be strong but the specific effect may even be harm-ful. One concerns the pressure on the surgeon to ”do something” such as operating even if it is im-possible to remove all of the tumour. Sometimes palliation can be achieved, but in others, the ’benefit’ is the patient’s knowledge that much of the tumour has been removed, even at the expense of a depres-sion of the immune system, which could lead to a more rapid spread. (329)

For some conditions there is an undocumented tradition of treatment that is seen as valuable and obviously effective also without documentation. It is considered un-ethical not to conduct such procedures and seen as a loss to the patient if they are not done (chapter 7). On the other hand it is considered unethical to carry out surgical procedures that are of no use to the patient seen in relation to the strain and risk they represent (331).

Regrettably there are examples of traditional procedures without any effect, also in the field of palliative surgery (laminectomy without fixation in spinal compression, palli-ative nephrectomy for flank pain), hence it always seems important to identify docu-mentation that is as good as possible. Because of the deficient knowledge basis, ex-treme caution should be exercised in relation to the danger of overtreatment. The Nor-wegian Cancer Plan (327) states that the danger of overtreatment is particularly great in symptom-oriented palliation (3.2.2.5). The crucial duty to help and to do everything that is possible also calls for soberness in assessing benefit against risk (benevolence).

This limited knowledge basis opens up for the danger of renouncing on the require-ment of scientific documentation, though it does call for research on palliative sur-gery. The Norwegian Cancer Plan made it clear that there is a considerable need for defining the knowledge basis and indications for palliative surgery. It seems that this has not been sufficiently followed up. The medical community has a special respons-ibility for taking stock of and analyse procedures that are considered “obviously use-ful” and of which it is thought that it would to be detrimental to patients if they go out of use.

With regard to preventive palliative surgery, the challenge with regard to uncertainty is particularly striking; not only is there uncertainty as to the effect of the treatment but also as to the extent to which the patient would have developed the assumed symptoms if he or she had remained untreated. Operating on an asymptomatic person with an incurable cancer who will need all available resources in order to meet the (uncertain) course of the disease requires a good justification and special caution.

5.3.4 The wish to do ”everything that is possible”

Many patients are of a persuasion that calls for doing “everything that is possible”. As long as one acts (operates), there is hope. If the physicians do not act, the patient could perceive it as “being given up by the health services”.

This wish, to do “everything that is possible”, is a challenge in several respects: it could reinforce a misconceived “duty to help” (overtreatment), it is also a challenge in

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relation to informing patients and their families (see below). A hard question is whether the patient has the ability to critically evaluate what “everything that is pos-sible” means. A thorough evaluation of the knowledge basis, risks and the possibility of overtreatment is usually not part the wish to have “everything that is possible” done. Many patients have great faith in the quality and control of modern medicine, including a faith in the options being many and good and the risk minimalised. Sur-gery in particular is the emblem of what modern medicine can achieve. Added to this: cancer is also a disease with a special symbolic character; metaphors like “fighting cancer” and “cancer crusade” are used. Fighting and crusading allow strong measures, though in many contexts it is the weakest who suffer the most.

In an era in which patient autonomy and patient rights are crucial concerns, many would claim that one should go far in complying with the wishes of patients and their families. The challenge arises when the benefit (and cost-benefit) of the relevant treat-ment is uncertain. Should we operate on patients “so that they do not lose their hope”? Is surgery, with its consequences, possible side effects and complications, the right way of instilling hope in patients? What is the role of information in this context?

5.3.5 Patient autonomy and information

Pursuant to the Norwegian Patients’ Rights Act (334)2, the patient is entitled to parti-cipate in the implementation of his medical treatment (section 2-1), has a right to be informed (section 3-2), and the right to give consent (section 4-1) to the health care that is given (section 4-1). Patients have the right to be informed about their situation, what the treatment implies, and of possible risks and side effects. Health personnel have a duty to provide such information adapted to the patient’s individual condition (section 3-5).

There are several reasons why this duty to inform is particularly difficult and import-ant in relation to cancer patients in general and to palliative surgery in particular:

a) There is limited knowledge (that is, documented effect) about the benefitb) The patient is especially vulnerable and with a limited ability to receive and un-

derstand informationc) The patient’s state of health could change rapidlyd) The risk related to some procedures could be considerable (perioperative mortal-

ity, postoperative infection rate, morbidity)e) There are great expectations to the effect that the health services will do

”everything that is possible” without there being nuanced views of what this means in terms of uncertain effect and risk

f) Patients could fear that they are being ”given up” by the health services if surgery is not done

g) There could be other types of palliation than surgery that are not well known.

Giving sober information without destroying hope or giving false hope is one of the most usual dilemmas in palliative surgery (333). It turns out that a large proportion of patients remember little of the information about risk that they got before certain oper-ative procedures (337,339). Patients also have difficulty understanding the reality they 2 http://odin.dep.no/hd/engelsk/news/new_publ/030071-200002/index-dok000-b-n-a.html

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are facing and this leads to a great deal of misunderstanding (339). The boundaries between information, persuasion and paternalism are not clear-cut when it comes to vulnerable patients. There being no alternatives is a source of confidence, but also of power (340).

Similarly, the circumstances listed under a–g above that pertain to patients’ right to participation, to consent to or refuse treatment (section 49) are real-life challenges. Is a very ill patient in a state in which he can exercise these rights? If the patient’s condi-tion is worsening, is it certain that he still wishes to undergo the procedure? What should be done when the patient does not find that he is capable of receiving informa-tion in such a situation? How well are sorrowful and despairing relatives able to take care of the patient’s interests? Will they tend to recommend that “everything that is possible” is done for those closest to them because of anticipated decision regret? In this respect, health personnel are facing great practical and fundamental problems.

5.3.6 Priorities

Pursuant to Norwegian Official Reports no. 18, 1997, the health services shall set pri-orities according to 1) severity, 2) benefits, and 3) cost efficiency. This is specified in the Patients’ Rights Act (334), from which it appears that the patient has a right to ne-cessary help if: 1) the patient either to some extent has a worse prognosis in terms of remaining lifespan if help is delayed, 2) the patient may have an expected benefit of the help, 3) expected costs are in a reasonable relationship to the effect of the treat-ment. Incurable cancer meets the requirement of severity. For most form of palliative surgery, the benefit is either poor or undocumented. This does not necessarily imply that there is no benefit, but that the requirement of documented benefit, b), is not filled. If the benefit is not known, nothing can be said about cost-benefit; c) the costs of palliative surgery are considerable (roughly estimated at 50% of the resources used on cancer surgery, cf. chapter 2.1). Solely on the basis of priority criteria, palliative surgery will not be given priority.

Lack of documented benefit is not unique for palliative surgery; it applies to a range of therapeutic modalities generally and to surgery in particular. This means that in set-ting priorities between surgical procedures, palliative surgery stands up reasonably well on the basis of severity. Some will maintain that there is a limit here: cure is more important than palliation. In the choice between a seriously ill patient who could be cured and a severely ill patient for whom there is only the potential for palliation, and in a situation in which the methods are otherwise just as badly or well docu-mented, one should give priority to the patient who has a potential for cure, among other things because he or she may live longer. In no way is it clear that one has reached this stage in setting priorities.

5.3.7 Research and ethics

The lack of knowledge about benefit and risk is a moral as well as a scientific chal-lenge. Some observers point to a paternalistic tradition in surgery as a reason for the lack of knowledge (324): surgeons have been accustomed to being able to take de-cisions, chose and develop methods for the benefit of their patients (paternalistically) without the need to document their usefulness. The lack of a knowledge basis to some

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extent could be seen as the outcome of a paternalistic tradition, the great expectations for the health services to do “everything that is possible”, the health services’ pre-paredness to act on the basis of the duty to help, the ”evident usefulness” of some pro-cedures, a long undocumented tradition for some methods, and lack of a tradition of research in some fields. This is, however, hardly a complete explanation.

There seems to be several methodological challenges in the field of palliative surgery. Patients’ state of health may change rapidly and, in consequence, so may treatment objectives. Other aspects that pose methodological problems are treatment and selec-tion bias, randomisation, surgical learning curves, grey zones in relation to emergency treatment, and variations between therapists. Documenting preventive palliative sur-gery seems to be particularly difficult (chapter 7).

There are a range of moral concerns related to these methodological problems:a) Some maintain that reexamining procedures that are considered ”evidently useful”

is immoral.b) Many consider placebo surgery immoral.c) Some think it immoral to included seriously ill people in research.d) It is problematic to obtain informed consent from the seriously ill.e) Assessing the effect of surgical intervention against best supportive care is seen as

immoral.

This has made some maintain that ethics stands in the way of knowledge enhancement in palliative surgery (324).

5.3.8 Knowledge and ethicsThe limited knowledge basis for palliative surgery represents moral challenges that may be seen in the light of different perspectives within normative ethics. If there is not enough knowledge about effect and risk, it is difficult to apply the principles of benevolence and non nocere. Consequence analysis of benefit and risk could be spec-ulative without an adequate knowledge basis. Correspondingly, in situations with lim-ited knowledge it is a challenge to respect the autonomy of patients, their right to par-ticipation in decision making, to give consent and receive good information. This is all the more difficult because of the patients’ condition.

Virtues such as compassion and mercy as well as the duty to help seem strong in rela-tion to this group of patients. The principle of justice and the prioritisation criterion of severity could also benefit palliative surgery, though areas with limited knowledge re-quire special caution.

There are, therefore, many ethical challenges that follow from the limited knowledge basis. To some extent the cause of the lack of documented knowledge can be traced to the necessary research being considered unethical. This might have a self-reinforcing effect and be seen as paradoxical: Lack of knowledge is unethical but so is also devel-oping new knowledge. This is hardly an adequate explanation. Providing the founda-tion for offering palliative surgery to patients on the basis of the best possible know-ledge is a methodological and moral challenge which the professional community must take seriously, also in relation to registration.

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Palliative surgery is a potentially valuable treatment for a group of patients that are particularly exposed. It is essential that these very vulnerable patients are not exposed to unnecessary treatment, that they get as good palliative care as possible, that their rights as patients are respected, in particular that they get as good information as pos-sible on effects as well as risks, and, as the case may be, on the lack of documentation of these factors. When the patient has a short remaining lifespan and there is great risk associated with a surgical procedure, non-surgical palliation will be the best alternat-ive.

Palliative surgery calls for a considerable degree of skills, in moral and communicat-ive terms as well as in surgical terms.

Addendum The Norwegian Cancer Society’s comments have been incorporated in the text above. They consider it important to bring out the issues related to treatment of patients with palliative needs. They see it as a strength that this theme is approached with a ques-tioning attitude with no hard conclusions. In particular they point to discussion and advice to patients and their families and the importance of communicating well. In-formation is important and knowledge about the benefits and risks is useful for those that are going to inform them. Patients and their families have a need to understand, to find a meaning and to find comfort in the belief in that all the best that can be done for them is done. The Society agrees that palliative surgery requires moral as well as sur-gical skills and good communication skills.

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6 Discussion

A cancerous tumour is no longer curable when it cannot be resected surgically or de-structed through radiotherapy or chemotherapy. Treatment of such cancerous disease is defined as palliative and aims at delaying or reducing symptoms and prolonging life. It is underscored that non-surgical treatment in many situations will be the best alternative, especially in situations when the patient has a short expected lifespan and the risk of a surgical procedure must be assumed to be great. In all cases of palliative surgery there is broad agreement that patients and their families should be involved in decision making. If such a joint assessment from patient and family shall be of more than symbolic value, opportunities and limitation of any palliative procedure must be as well documented as possible.

Because symptomatic treatment, not cure, is the objective in palliative surgery, the SMM and its group of experts have chosen to concentrate efforts on two main prob-lems: The effect of procedures that reduce symptoms from various organ systems, ir-

respective of the origin of the primary tumour. The effect of procedures that aim at preventing well-known future symptoms from

an incurable primary tumour.

This approach may be exemplified by palliative thoracic surgery. Instead of going through all procedures of thoracic surgery and check which of these are documented in palliative cancer problems or examine the results of surgical procedures done on thoracic structures and isolate those who may be palliative, one has focused on those thoracic symptoms that thoracic surgeons are particularly equipped to take care of. This reduces the scope to three main problems: difficulty breathing, obstruction of the superior vena cava, and prolonging life through excision of lung metastases.

The most difficult assessment in palliative surgery is the use of procedures that may prevent or delay symptoms. This requires extensive knowledge of the “natural” course of the disease and defined endpoints of the effectiveness of the procedure. Knowledge about the course of the disease will usually be based on post hoc statistical estimates and cannot with certainty be applied to the individual patient. Prophylactic procedures should be simple, have a reliable effect, and low risk of complications.

The group of experts finds that this approach is a better reflection of the real clinical situation within palliative surgery. Textbooks usually focus on primary tumour types in a single organ, staging, procedures and survival, with strikingly little focus on and evaluation of the problem of palliation. Surgeons are therefore often left with their colleagues’ and their own experience as a supplement to a literature that is hard to sur-vey and of doubtful quality. Palliative surgery is not a small and sporadic practice but a substantial part of the surgical approach to cancer, hence this is an activity that will benefit from a systematic review of and standardisation of methods that will be of help in the evaluation of the individual patient.

The structure on which surgical specialisation in Norway is based is also reflected in the composition of the group of experts. The subspecialties have explained in detail what studies are available on their respective palliative problems and in conclusions

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summed up the basis of evidence for their respective treatments. In the first part of the project, when a search strategy was developed and the first results were obtained, it became clear that palliative procedures in gynaecologic cancer so much involved urin-ary tracts and the intestine that it was a natural thing to do for surgeons in these field to evaluate the documentation on palliative procedures. This is underlined by the Co-chrane review of reports on malignant intestinal obstruction, in which metastases from ovarian cancer were the largest group (20). Metastases that threaten the spinal channel are an area in which neurosurgeons and orthopaedists have overlapping skills. In such areas, experts from both fields have independently assessed and classified the avail-able documentation. It turned out that there was full agreement between the two groups with the exception of one article (129), which was excluded by the ortho-paedist on the grounds that it included too few patients.

For some widely used palliative procedures there is no documentation of effect in the available databases (which often cover only the last 15 to 25 years); examples are pal-liative transurethral resections for bleeding of the mucosa of the urinary bladder or the prostate. Still it would have been beneficial for patients if one systematically re-gistered effect, complications and limitations and studied combinations with other methods. There is little reason to question the effect of the transurethral methods men-tioned, but an undocumented therapeutic tradition also carries a risk that less effective procedures that require a great deal of resources are carried on with. Laminectomy without fixation in impending or manifest spinal compression is a traditional method which a review of documented effects clearly shows is inferior to other methods for relieving pressure.

Under optimal conditions, palliative cancer surgery should be evidence-based. As it will appear from the results presented in this report, this is only in exceptional cases the case. There is little reason to believe that this will change radically in the foresee-able future, because the primary scientific method, randomised clinical trials, is gener-ally difficult (but not impossible) to apply in the evaluation of surgical procedures, and because a randomisation between active (surgical) and palliative supportive treat-ment poses great practical and ethical problems. Compulsory registration of cancer surgery as palliative and/or potentially curative would obviously be an improvement in relation to present practice.

With a figure or a letter included with the necessary release of a surgical DRG code, the basis for future evaluation of effects could be greatly improved. With a link to the Norwegian Cancer Registry, the cost of palliative surgery could easily be estimated, as well as median lifespan and variations and prevention of the symptoms that require treatment. A longitudinal registration such as this would be a better way of mirroring the population’s needs and problems than randomised studies, which always have an inclusion-based bias.

Our primary objective, as will appear from our terms of reference, not been achieving consensus, but assessing the documentation available. Because there is usually no documentation of particular problems that makes it possible to determine the absolute value of a method, we have focused on a “best evidence” approach. This means that we started out with broad search criteria and included prospective as well as retro-spective studies. The large number of excluded studies in the final assessment is the result of a wish to start out with all studies that might be relevant to the problem. This

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approach appreciably prolonged the time period needed for the project. In order to avoid that new documentation published during the project period was not included in the assessment, a final attempt at updating was conducted in February 2003. Although a few reports were identified, there are still no major international assessments that satisfactorily answer the questions that are included in our terms of reference.

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