evidence-based guideline recommendations on the use of positron emission tomography imaging in...

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Clinical Oncology 24 (2012) 232e249

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Clinical Oncology

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Guidelines

Evidence-based Guideline Recommendations on the use of Positron EmissionTomography Imaging in Colorectal Cancer

K. Chan *, S. Welch y, C. Walker-Dilks z, A. Raifu z* Sunnybrook Odette Cancer Centre, Toronto, Ontario, CanadayDepartment of Oncology, University of Western Ontario, London Health Sciences Centre, London, Ontario, Canadaz Program in Evidence-Based Care, Cancer Care Ontario (CCO), McMaster University, Hamilton, Ontario, Canada

Received 11 February 2011; received in revised form 17 October 2011; accepted 23 November 2011

Abstract

Aims: To provide evidence-based practice guideline recommendations on the use of fluoro-2-deoxy-D-glucose positron emission tomography (PET) for diag-nosis, staging, assessing treatment response, liver metastasis and restaging or recurrence of colorectal cancer.Materials and methods: A systematic review by Facey et al. (Health Technology Assessment 2007;11(44):iiieiv, xie267) was used as the evidence base forrecommendation development. As the review was limited to August 2005, the evidence base was updated to May 2010 using the same search strategies forMEDLINE and EMBASE used in the original review. The authors of the current systematic review drafted recommendations, which were reviewed, adapted andaccepted by consensus by the Ontario provincial Gastrointestinal Disease Site Group and a special meeting of clinical experts.Results: The results from the Facey et al. review for colorectal cancer included three other systematic reviews and 24 primary studies. The 2005 to 2010 updatedsearch included 10 additional systematic reviews and 28 primary studies. Recommendations were developed based on this evidence and accepted by consensus.Conclusions: The routine use of PET is not recommended for the diagnosis or staging of clinical stage IeIII colorectal cancers. PET is recommended fordetermining management and prognosis if conventional imaging is equivocal for the presence of metastatic disease. PET is also not recommended for routinesurveillance in patients with colorectal cancer treated with curative surgery at high risk for recurrence. It is recommended to determine the site of recurrence inthe setting of rising CEA when conventional work-up fails to unequivocally identify metastatic disease. Finally, PET is recommended in the preoperativeassessment of colorectal cancer liver metastasis before surgical resection.� 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Key words: Colorectal cancer; diagnosis; FDG-PET; liver metastases; recurrence; staging

Introduction

Colorectal cancer (CRC) is the thirdmost common cancer,with an estimated 22,500 new cases and 9100 deaths for2010 in Canada [1]. According to Canadian cancer statistics[1] for 2010, CRC is the second cause of death from canceramong both men and women. The mortality due to CRC inCanada has gradually declined since 1986 by�1.2 and�1.7%in males and females, respectively [1]. The decline in CRC

Author for correspondence: C. Walker-Dilks, Cancer Care Ontario,Program in Evidence-Based Care, McMaster University, Juravinski HospitalSite, G Wing, 2nd Floor, 711 Concession Street, Hamilton, Ontario L8V 1C3,Canada. Tel: þ1-905-527-4322x42847; Fax: þ1-905-526-6775.

E-mail addresses: [email protected], [email protected](C. Walker-Dilks).

0936-6555/$36.00 � 2011 The Royal College of Radiologists. Published by Elsevdoi:10.1016/j.clon.2011.11.008

mortality since 1986 has been attributed to the treatment ofthe cancer through chemotherapy.

The use of positron emission tomography (PET) asa major diagnostic imaging tool for cancer is on the increasein the USA, Canada, Europe and parts of Asia. Differentstudies have suggested that PET may perform better thanother technological imaging modalities like X-ray,computed tomography (CT) and magnetic resonanceimaging (MRI) in some circumstances.

Because of the promising results on the use of PET for thediagnosis, staging and detection of recurrence of CRC andother cancers in the literature, the Ontario PET SteeringCommittee made a special request to the Clinical Council ofCancer Care Ontario to co-lead the development of guid-ance regarding the clinical use of PET imaging. The Programin Evidence-Based Care (PEBC), worked with the PEBC

ier Ltd. All rights reserved.

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K. Chan et al. / Clinical Oncology 24 (2012) 232e249 233

Disease Site Groups (DSGs) to synthesise the clinicalresearch and to draft recommendations for 10 disease sites(brain, cervical, colorectal, oesophageal, head and neck,melanoma, ovarian, pancreatic, small cell lung cancer, andtesticular).

The target population for this review and clinical practiceguideline is patients with CRC. Its purpose is to find answersto the following research questions:

� What benefit to clinical management does PET or PET/CT contribute to:

B The diagnosis or staging of CRC?B The assessment of treatment response for CRC?B The assessment of recurrence of CRC is suspected

but not proven?B The restaging at the time of the documented

recurrence for CRC?B The assessment of a solitary metastasis is identi-

fied at the time of recurrence and a metastectomyis being contemplated?

As these questions were identified to guide the devel-opment of guidelines across all cancers, they may not beequally relevant in the consideration of CRC. The objectiveof these questions is to provide evidence-based recom-mendations on the use of fluoro-2-deoxy-D-glucose (FDG)PET for diagnosis, staging, assessing treatment response,liver metastasis and restaging or recurrence of CRC. Theserecommendations will be useful in informing clinicaldecision making regarding the appropriate role of PETimaging and in guiding priorities for future PET imagingresearch.

Materials and Methods

In order to develop the recommendations and achieveconsensus, two methodological approaches were under-taken; systematic review and formal consensus. Althoughthis paper concentrates on the identification of evidenceand the development of recommendations with respect toCRC, in fact the process was conducted for all the cancersmentioned above simultaneously.

Systematic Review

Literature Search

A scoping review undertaken by a PEBC methodologistto identify any existing systematic reviews on PETimaging in the cancers of interest yielded such a review.A systematic review by Facey et al. [2] evaluated theeffectiveness of (FDG-PET) imaging in several selectedcancers, including CRC. It included systematic reviews andprimary studies dating from 2000 to August 2005.Because the Facey et al. review [2] sufficiently covered theevidence of interest to address the questions identifiedabove, its results were used for the evidence base from2000 to August 2005, and its search strategies were

carried out in MEDLINE and EMBASE to update theliterature to May 2010. The search strategies used areavailable upon request from the corresponding author ofthis review.

Study Selection Criteria

All systematic reviews and primary studies in the Faceyet al. review [2] that addressed the questions of interest inthis current review (diagnosis, staging, treatment response,recurrence and restaging) with respect to CRC wereincluded. The inclusion criteria of the Facey et al. review [2]were used to select systematic reviews and primary studiesidentified in the updated search. These criteria were asfollows.

Other systematic reviews were included in theupdate if:

� They were dedicated to FDG-PET in CRC in humans;� They contained evidence related to diagnostic accuracy,change in patient management, clinical outcomes ortreatment response.

Primary studies were included in the update if:

� They were prospective clinical studies of FDG-PET inCRC;

� They were published after the end date of the search inthe Facey et al. review [2];

� They were published as a full article in a peer-reviewedjournal;

� They reported evidence related to diagnosticaccuracy, change in patient management, or clinicaloutcomes;

� They included �12 patients with CRC;� They used a suitable reference standard (pathologicalconfirmation and clinical follow-up) when appropriate.

The citations and abstracts from the updated searcheswere reviewed by a PEBC methodologist and marked asrelevant or not according to the inclusion criteria. Themethodologist and the clinical lead authors reviewed therelevant citations and the full text of the articles tomake thefinal decision on inclusion.

Synthesising the Evidence

The Facey et al. review [2] did not pool individualstudies, and no meta-analysis of studies from the updatedsearch was planned due to an a priori expectation ofheterogeneity among the studies. Facey et al. [2] extracteddata into separate tables for systematic reviews andprimary studies for each type of management decision. Thesame approach was used for data extraction for theevidence from the updated search. Full text and dataextractions of the studies from the updated search wereprovided to the clinical lead authors to aid in the formu-lation of the recommendations.

K. Chan et al. / Clinical Oncology 24 (2012) 232e249234

Consensus

Disease Site Group Consensus Process

The clinical lead authors wrote a summary of the keyevidence and drafted initial recommendations and qual-ifying statements with respect to the research questions.Because of the special interest of the GastrointestinalDSG, an initial recommendation was also drafted per-taining to the use of PET in CRC liver metastasis. Theensuing documents were circulated to all members ofthe Gastrointestinal DSG and discussed during a telecon-ference. The recommendations that were generatedduring this process are referred to below as the draftDSG recommendations. The intent of these recommen-dations was to guide discussion at the consensusmeeting.

Provincial Consensus Process

The consensus meeting on 19 September 2008 wasconducted as follows:

� Consensus meeting participants sat at tables set up todiscuss a particular disease site. Participating at theCRC table were the two clinical leads, other DSGmembers attending, and other invited healthprofessionals.

� The recommendations and summary of key evidencedrafted by the clinical lead authors and refined andconfirmed by the Gastrointestinal DSG were presentedby the clinical leads to the group at the colorectaltable.

� During small-group discussion at the colorectal tablein the morning and discussion among all entireconsensus meeting participants in the afternoon, therecommendations underwent further refinement andmodification. The attendees then voted on the revisedrecommendations to indicate their extent of agree-ment on a scale from 1 to 9 (1 indicating strongagreement, 5 indicating no agreement or disagree-ment, and 9 indicating strong disagreement). Theattendees’ ratings were used to assess the level ofconsensus achieved by the meeting participants oneach recommendation.

After the consensus meeting, the exact wording of therecommendations was edited for consistency with therecommendations resulting from the other disease discus-sions. These modifications included using emphatic,unambiguous language (i.e. PET is recommended.) andremoving the need to distinguish between PET and PET/CT.It was made clear at the consensus meeting that PETimaging alone is being phased out and PET/CT imaging isthe current standard. Thus, the term PET is used to coverPET and PET/CT imaging. These recommendations thatresult from this consensus process are referred to below asthe final recommendations.

Results

Literature Search Results

The results from the Facey et al. review [2] for CRCincluded three other systematic reviews and 24 primarystudies. The 2005 to 2010 updated searches included eightrecently published systematic reviews and 28 primarystudies. Data extracted from the other systematic reviewsand primary studies in the Facey et al. [2] are available onthe UK Health Technology Assessment website (http://www.hta.ac.uk/1487). Data extracted from the primarystudies from the updated search are in the Appendix. Noneof the recently published systematic reviews [3e9] from theupdated search provided any additional evidence to thatextracted from the primary studies, so they are not dis-cussed further. The key evidence identified from the Faceyet al. review [2] and the primary studies from the updatedsearch are described below.

Key Evidence

DiagnosisOne systematic review of two primary studies and one

additional primary study in the Facey et al. review [2]summarised that PET has good sensitivity to detectprimary tumours >2 cm, but not smaller tumours, withvariable specificity. No additional studies were identified inthe 2005e2010 updated search.

StagingTwo primary studies in the Facey et al. review [2] and

four studies [10e13] from the updated searches wereidentified. These studies had different patient case mixesand proportions of patients with stage IV disease. Althoughsome studies showed changes in patient managementbecause of changes in M-staging, such findings were instudies with a relatively large proportion of stage IV disease.The studies by Furukawa et al. [10] and Nahas et al. [11] didnot show any significant changes in M-staging. Kosugi et al.[12] included 53 patients with lymph node metastases onCT. PET detected 24 para-aortic, 29 epicolic/paracolic/orintermediate lymph node. The results of the Kosugi et al.study [12] showed that PET has lower sensitivity, higherspecificity, higher accuracy and higher positive predictivevalue than CT for N1 and N2e3 lymph nodes. For N4 lymphnodes, PET has high sensitivity and high specificity, whereasCT has only high sensitivity but low specificity and lowpositive predictive value. Thus, it is reasonable to considerusing PET when N4 nodes are suspected.

The Facey et al. review [2] did not identify any studiesthat involved the use of PET/CT exclusively for stagingbefore any therapy. The 2005e2010 updated search iden-tified four studies [14e17]. Park et al. [14] included onlypatients with equivocal CT findings or elevated Carci-noembryonic antigen (CEA), which resulted in 49% stage IVpatients. PET/CT changed management in 24%. Tsunodaet al. [15] evaluated the detection rate of PET/CT with

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http://www.hta.ac.uk/1487


respect to nodal metastasis (proximal and distal). PET/CThad better performance than CT overall. Given the smallproportion of patients with distant nodal metastasis plusthe fact that the study did not separately compare PET/CTand CT with respect to distant nodal metastasis only, it isdifficult to know whether distant nodal M-staging ischanged significantly with the use of PET/CT. Studies byVeit-Heibach et al. [16] and Kinner et al. [17] did not showa significant change in M-staging.

The updated searches identified one primary study [18]that included 467 patients. There was concordance amongPET, CT and PET/CT in 91.2% of the cases. Seventy-two percent of the cases were true positive for liver metastases,suggesting that the patients in the study had a higher indexof suspicion for liver metastases than might be expected inthe routine clinical setting. The study provided a formalstatistical Z test comparison, which showed that PET/CT isbetter than PET or CT alone with P-values < 0.05. Thesensitivity and specificity were all greater than 90% in CT,PET and PET/CT.

Assessment of treatment responseThe updated search identified a randomised control trial.

Bystrom et al. [19] evaluated PET before and after two cyclesof chemotherapy and also evaluated CT before and after fourcycles of chemotherapy. The results showed that PETcorrelated with CT and has relatively low sensitivity andspecificity. PET also failed to predict the time to progressionor overall survival in patients with metastatic CRC. Thestudy suggested that PET should not be used as a substitutefor CT for short-term response assessment and should notbe used as a surrogate for long-term clinical end points. TheFacey et al. review [2] identified six non-randomised studiesshowing that changes in standardised uptake values (SUV)between pre-therapy and post-therapy scans may predictresponse. The updated search identified four additionalprimary studies evaluating treatment response. One-timePET after preoperative therapy poorly predicteda complete pathological response after preoperativetherapy in the studies by Capirici et al. [20] and Kalff et al.[21] and poorly predicted post-therapy staging in Casciniet al. [22]. Glazer et al. [23] conducted a prospective cohortstudy of 138 patients with presumptive diagnosis of livermetastasis that had at least one PET scan after chemo-therapy and before liver resection. The study showed thatultrasonography also guides surgical decision makingduring intraoperative assessment and suggested that PETafter chemotherapy should not be used in decision makingfor liver resection.

The updated search identified two studies [24,25].Capirci et al. [24] suggested that a change in SUV before andafter preoperative chemoradiotherapy predicted tumourregression grade in rectal cancer, whereas Kristiansen et al.[25] suggested that a single PET/CT after preoperativetherapy poorly predicted a complete pathological response.

Recurrence/restagingThe review by Facey et al. [2] identified one other

systematic review that included 13 primary studies and two

additional primary studies. Overall, these studies showedthat PET had sensitivity for detecting recurrence of �85%and specificities varying from 43 to 90%. Accuracy andsensitivity were superior to CT and similar to MRI. Twostudies noted that PET’s ability to detect lesions <1 cmwaspoor. The updated search identified one randomisedcontrolled trial [26] that evaluated the role of PET in thesurveillance of CRC in patients who underwent curativesurgery and were at high risk for recurrence. Overall, therewas no difference in recurrence rate with the addition ofPET to conventional work-up, but there was a significantimprovement in the time to detection of recurrence and innumbers of patients treated with potentially curativesurgery. The small sample size (n ¼ 130) precludes defini-tive conclusions on the role of PET as part of surveillance inCRC.

Liver Metastasis

In the Facey et al. review [2], one other systematic reviewthat included nine primary studies and five additionalstudies in primary and recurrent populations showed PET tobemore accurate than comparators for the detection of livermetastases. Furthermore, in 15 studies of mixed pop-ulations, including patients with suspected recurrence, PETsensitivity was about 90% compared with 73% sensitivity forCT. PET specificity was �85%. A change in managementattributed to PET (compared with conventional imaging)varied from 9 to 39% in the reported studies. Two studies inFacey et al. [2] noted that 6 and 15%, respectively, hadstaging incorrectly changed.

The updated search identified one randomised study[27] that considered 150 patients with CRC liver metastasiseligible for potentially curative surgery. This study sug-gested a significant decrease in futile laparotomy (45%versus 28%) when FDG-PET was added to the preoperativeimaging strategy. Seven additional non-randomisedstudies [28e36] were identified in the updated searchthat evaluated the use of PET in these patients. Rappeportet al. [28] showed that CT and MRI were more sensitive butless specific than PET/CT in the detection of liver metas-tases. However, PET/CT was more sensitive and specific forthe detection of extrahepatic metastasis than CT alone. Inthe study by Huguet et al. [29], PET had higher sensitivitythan CT for hepatic, pulmonary and extrahepatic/extrap-ulmonary sites. Clinical management was changed in nineof 31 patients (29%) and was attributed to the results ofPET. Liu et al. [30] supported the superiority of PET/CT overcontrast-enhanced CT for the detection of metastaticlesions of CRC. Kitajima et al. [31] showed that integratedPET/contrasted-enhanced CT is an accurate modality forassessing CRC recurrence and led to changes in thesubsequent therapy. Potter et al. [32] recommendeda serial imaging review with careful correlation of suspi-cious findings with previous studies in suspected recur-rence. Only the study by Adie et al. [33] suggested thatpreoperative assessment with PET/CT is not useful forhepatic colorectal metastases, particularly when preoper-ative chemotherapy is used, with a trend towards an


underestimation of lesions. Therefore, PET/CT is a usefultool when findings remain equivocal after a serial imagingreview for CRC.

Recommendations

Consensus Recommendations

Diagnosis/stagingThis draft DSG recommendation was:

� The routine use of PET or PET/CT is not indicated for thediagnosis or staging of clinical stage IeIII CRC.

During the Provincial Consensus Meeting deliberations,although therewas agreement in principle with this recom-mendation, there was debate in the small-group discussionand again in the large-group discussion around puttingforward a recommendation for PET in the initial assessmentof rectal cancer to determine N-stage for consideration ofneoadjuvant locoregional chemoradiation. However, it wasagreed insteadto include this asanarea for futureresearch. Inthesmall-groupdiscussion,andconfirmedinthelarge-groupdiscussion, the suggestion was to include a second recom-mendation regarding a role for PET in determining themanagement and prognosis of patients if conventionalimaging is equivocal for the presence of metastatic disease.

Assessment of treatment responseThe draft DSG was:

� The routine use of PET or PET/CT in locally advancedrectal cancer before and after preoperative chemo-radiotherapy is not indicated.

The extent of agreement with this recommendationduring the Provincial Consensus Meeting deliberations wasfairly strong, and no major issues were raised during thesmall- or large-group discussion. It was suggested thata trial may be needed to confirm this recommendation.

Recurrence/restagingThe draft DSG recommendations were:

� PET is not indicated for routine surveillance in patientswith CRC treated with curative surgery at high risk forrecurrence.

� PET is recommended to determine the site of recurrencein the setting of rising CEA or suspicious symptomswhen conventional work-up fails to unequivocallyidentify metastatic disease.

The extent of agreement with these recommendationsduring the Provincial Consensus Meeting deliberations wasfairly strong. The suggestion was made to remove ‘suspi-cious symptoms’ from the second recommendation and oneparticipant was concerned with the non-specificity of thisstatement.

Liver metastasisThe DSG suggested this draft recommendation:

� PET is indicated in the preoperative assessment beforesurgical resection of CRC liver metastasis.

There was discussion during the Provincial ConsensusMeeting deliberations about a randomised controlled trial(PETCAM) on this topic, which was ongoing at the time,because this recommendation could affect accrual. Thepossibility of evidence to support the use of PET for thisindication might be an ethical reason to end the trial. Thesuggestion was made that the safety monitoring board ofthe trial should be consulted. It is acknowledged that theresults of the PETCAM randomised trial, when available,could result in a change to the recommendation concerningPET in the preoperative assessment of CRC liver metastasesbefore surgical resection.

Final Recommendations

After recommendations were put to vote during themeeting, these final recommendations were confirmed:

� The routine use of PET is not recommended for thediagnosis or staging of clinical stage IeIII CRC.

� PET is recommended for determining management andprognosis if conventional imaging is equivocal for thepresence of metastatic disease.

� The routine use of PET is not recommended for themeasurement of treatment response in locally advancedrectal cancer before and after preoperative chemothe-rapy.

� PET is also not recommended for routine surveillance inpatients with CRC treated with curative surgery at highrisk for recurrence.

� PET is recommended to determine site of recurrencein the setting of rising CEA when conventionalwork-up fails to unequivocally identify metastaticdisease.

� PET is recommended in the preoperative assessment ofCRC liver metastasis before surgical resection.

Discussion

Some studies evaluated the diagnostic performance ofPET or PET/CT with respect to each metastatic site/organ/lesion, whereas some evaluated it with respect to the M-staging of each patient. It would seem that studies thatanalysed results based on each site/organ/lesion showeda better performance of PET or PET/CT, whereas studiesthat analysed results based on the overall M-staging ofpatients did not show an obvious improvement inperformance of PET or PET/CT. As solitary or oligo-metastasis is not a very common presentation in theinitial diagnosis of CRC, it would be unlikely that PET orPET/CT would detect such a situation when CT missed it, ifthe analysis was to change M-staging and the


management of these patients. However, in patients whoalready have suspicious or confirmed metastasis based onCT, it is quite possible that PET or PET/CT could detectfurther metastases in other sites/organs that were notconclusively detected by CT alone. This will inflate thediagnostic performance of PET or PET/CT if analysis wasbased on sites/organs/lesions instead of overall M-stagingof each patient. This factor may be important whenmaking recommendations for early-stage disease versusmetastatic disease.

On the other hand, for patients who already have whatappears to be solitary or oligo-metastases on CT only, andwho are potential candidates for resection, and given thatthe possibility of further metastasis in other sites/organs isnot low, PET or PET/CT may assist in the decision making ofresection with curative intent by helping to assess theextent of metastasis. Studies that analysed the diagnosticperformance of PET or PET/CT with respect to sites/organs/lesions provided evidence to support this approach.Therefore, there may be a role for the use of PET or PET/CTwhen conventional imaging raises suspicion of the pres-ence of potentially resectable metastatic disease, andpatients are potential candidates to undergo such surgery.The incremental benefit of PET or PET/CT over MRI of theliver is unclear in such populations as none of the studiesincluded the routine use of MRI as part of conventionalimaging.

Most studies that showed that PETor PET/CTchanged themanagement of a significant proportion of patientsincluded a relatively large number with stage IV disease (upto 46% of patients). Studies that included a relatively smallproportion of stage IV patients did not appear to showa significant benefit or change in the patient managementplan with PET or PET/CT. Some of those changes inmanagement involved the detection of a larger than ex-pected volume of disease in the liver or extrahepaticmetastasis by PETor PET/CT in patients originally diagnosedwith low-volume resectable liver metastasis by conven-tional imaging.

Most studies that compared PET or PET/CT withconventional imaging were carried out in the time periodwhen multi-detector CT (MDCT) was not yet widelyavailable. The only study that clearly stated that MDCTwas used [10] did not show clinically relevant superiorityof PET in addition to MDCT. As MDCT is being usedroutinely in most of the cancer centres and hospitals inOntario, the incremental benefit of PET or PET/CT forroutine staging of CRC remains to be established.Although some studies reported the numerical compari-sons of diagnostic performance between PET (or PET/CT)and conventional imaging, few studies tested whether thenumerical differences observed were statistically signifi-cant or not.

It is unclear whether PET or PET/CT leads to animprovement in survival or simply results in stage migra-tion. Nonetheless, many practitioners may accept that more

accurate staging will lead to a better choice of treatmentplan, thereby avoiding overtreatment and sparing patientsthe unnecessary risk or side-effects of therapy or avoidingunder-treatment when patients might otherwise benefitfrom aggressive curative-intent therapy.

There are very few studies that evaluated rectal cancerand colon cancer separately. The current limited evidencedid not obviously suggest or refute that PET or PET/CTsignificantly changed management in patients with non-metastatic rectal cancer. However, some studies seemedto suggest that PET or PET/CT has better N-stage accuracythan CT. It is unclear how PET or PET/CT compares with MRIor trans-rectal ultrasound with respect to N-staging. Theremay be a role of PET/CT with respect to N-staging in thedecision making for patients with non-metastatic rectalcancer who may be candidates for preoperativechemoradiotherapy.

When conventional imaging with CT suggests equivocalpara-aortic lymph node involvement as the only potentialsite of concern and that the patient is otherwise a potentialcandidate for curative intent surgery of the primary CRC,PET can be considered to rule in or out metastatic disease inthe para-aortic region.

Despite the change in management reported in the non-randomised studies of PET in the evaluation of livermetastases, the possibility cannot be ruled out that factorsother than PET results were involved in that change. In theevaluation of patients potentially eligible for curativeresection of CRC liver metastasis, a diagnostic CT is neces-sary in addition to PET/CT to provide information on hepaticvasculature and anatomy.

The sensitivity of PET for detecting liver metastasesdecreases after neoadjuvant chemotherapy in patients withCRC liver metastasis [34]. If PET is to be used for stagingpurposes, it should be carried out before the start of neo-adjuvant chemotherapy.

Review and Update

Practice guidelines developed by the PEBC are reviewedand updated as required. Please visit the Cancer CareOntario website (www.cancercare.on.ca) for the full reportand subsequent updates.

Acknowledgements

This work was supported by the Ontario Ministry ofHealth and Long-Term Care through PEBC, a provincialinitiative of Cancer Care Ontario. This work is editoriallyindependent from its funding source. The authors wouldlike to thank the members of the Gastrointestinal DSG fortheir contributions to the development of this practiceguideline. We also thank Mr Afshin Vafaei for his previouswork on this article.

http://www.cancercare.on.ca

AppendixPositron emission tomography (PET) for colorectal cancer (CRC): summary of the primary study evidence from 2005 to 2010

Reference Objective No.patients

PET Reference test Comparisontest

Blinding Key results Authors’ conclusions

Diagnosis/staging[18] To compare the

diagnosticaccuracy of FDG-PET and CT withPET/CT in thedetection of livermetastasesduring tumourstaging inpatients sufferingfrom CRC for thepurposes ofcorrect surgicalplanning andfollow-up.

467 FDG-PET Histopathologyor clinicalfollow-up

CT and FDG-PET

Radiologist andnuclear physicianwere double blinded

PET: sensitivity ¼ 94.05% (95%CI 91.52e96.58%),specificity ¼ 91.60% (95% CI86.85e96.35%),accuracy ¼ 93.36% (95% CI91.10e95.62%), PPV ¼ 96.64%(95% CI 94.69e98.59%),NPV ¼ 85.71% (95% CI79.92e91.51%)CT: sensitivity ¼ 91.07% (95% CI88.90e94.12%),specificity ¼ 95.42% (95% CI91.84e99.00%),accuracy ¼ 92.29% (95% CI89.87e94.71%), PPV ¼ 98.08%(95% CI 96.55e99.60%),NPV ¼ 80.65% (95% CI74.43e86.86%)PET/CT: sensitivity ¼ 97.92%(95% CI 96.39e99.44%),specificity ¼ 97.71% (95% CI95.15e100.00%),accuracy ¼ 97.86% (95% CI96.55e99.17%), PPV ¼ 99.10%(95% CI 98.08e100.00%),NPV ¼ 94.81% (95% CI91.07e98.56%)

PET/CT is very usefulin staging andrestaging patientssuffering from CRC. Itwas particularlyuseful whenrecurrences could notbe visualised eitherclinically or byimaging despiteincreasing tumourmarkers, as itguaranteed an earlierdiagnosis. PET/CT notonly provides highdiagnosticperformance in termsof sensitivity andspecificity, enablingmodification ofpatient treatment, butit is also a unique,high-profileprocedure that canproduce cost savings.

[16] To evaluate thediagnosticaccuracy ofPET/CT in stagingCRC comparedwith CT aloneand CT followedby PET

47 PET/CT fromskull to upperthigh

Histopathologyor clinicalfollow-up(M1 patients)

CT aloneCT followed byPET

All participatingphysicians blinded toother imaging results,colonoscopy andhistopathology

PET/CT (see data extractionforms for CT and CTþPETresults):Tumour detection:sensitivity ¼ 98%,specificity ¼ 75%, PPV ¼ 98%,NPV ¼ 75%N-stage: sensitivity ¼ 80%,specificity ¼ 97%, PPV ¼ 94%,NPV ¼ 88%M-stage: sensitivity ¼ 100%,specificity ¼ 100%, PPV ¼ 100%,NPV ¼ 100%

PET/CT is at leastequivalent to CTfollowed by PET fortumour staging.

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[14] To assess the useof PET/CT in theevaluation ofprimary CRC andto evaluate theimpact onchanges to thetreatment plan

100 PET/CT fromhead toabdomen

Histopathologyand clinicalfollow-up

CT NR Identification of metastaticdisease: 13 true negative, 10false positive or false negativePET/CT results changedtreatment modality in 9patients: 8 true positive, 1 falsenegative.PET/CT changed extent ofsurgery in 18 patients. In 10patients with increasedoperative intent: 8 truepositive, 2 false positive. In 8patients in whom unnecessaryprocedure prevented: all 8 truepositive

PET appears toaccurately changetumour stage in one-third of patients andalter therapy in aboutone-fifth.

[10] To evaluate theadditional valueof PET asa stagingmodalitycomplementaryto routine CT

44 FDG-PET fromskull base togroin

Histopathology CT andmacroscopicdiagnosis

PET interpretationblinded to patients’medical history andCT.Pathologists blindedto preoperative PETand CT.

Tumour detection rate: 100%for PET, 95% for CT, 100% formacroscopic diagnosis.N-stage (PET):sensitivity ¼ 37%,specificity ¼ 83%, PPV ¼ 70%,NPV ¼ 43%, accuracy ¼ 59%N-stage (CT): sensitivity ¼ 58%,specificity ¼ 67%, PPV ¼ 65%,NPV ¼ 60%, accuracy ¼ 62%

PET is not superior toroutine CT in theinitial staging ofprimary CRC.

[13] To evaluate PETin initial stagingcompared withconventionalstaging methods

104 FDG-PET Histopathologyor clinicalfollow-up

CT PET and CTinterpretation blindedto other imagingresults

N-stage: sensitivity ¼ 21%,specificity ¼ 95%, PPV ¼ 83%,NPV ¼ 51%, accuracy ¼ 56%M-stage: sensitivity ¼ 89%,specificity ¼ 93%, PPV ¼ 73%,NPV ¼ 98%, accuracy ¼ 92%PET changed tumour staging in13.46% of patients, modifiedscope of surgery in 11.54%, andled to change in therapeuticapproach in 17.85%

PET appears to beuseful in pre-surgicalstaging comparedwith conventionaltechniques.

[17] To assess PET/CTfor staging CRC

55 PET/CT fromskull base toupper thighs

Histopathology CT NR PET/CT:TNM staging accuracy ¼ 74%,T-stage accuracy¼ 84%, N-stageaccuracy ¼ 82%CT:TNM staging accuracy ¼ 44%,T-stage accuracy¼ 70%, N-stageaccuracy ¼ 68%PET/CT significantly moreaccurate than CT

Staging patients withPET/CT is feasible, hasaccurate tumourdetection rates andshows promisingstaging results.

[15] To assess thediagnostic valueof PET/CT for

88 FDG-PET/CTfrom skull baseto pelvic floor

Histopathology None PET interpretationblinded to clinicalinformation

Visual diagnosis:sensitivity ¼ 28.6%,specificity ¼ 92.9%,

PET is useful for thedetection of distantlymph node

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lymph nodemetastases ofCRC

accuracy ¼ 75.0%Size diagnosis (cut-off point10 mm): sensitivity ¼ 30.6%,specificity ¼ 95.3%,accuracy ¼ 74.4%SUV diagnosis (cut-off point1.5): sensitivity ¼ 53.1%,specificity ¼ 90.6%,accuracy ¼ 80.1%

metastases. SUV isa better diagnosticcriterion thanabnormal FDG uptakeor nodal diameter.

[11] To determine theaccuracy of PETin detectingdistant disease inpatientsotherwiseeligible forneoadjuvant CRT

93 FDG-PET Surgicalexploration,clinical follow-up, imaging orhistopathology

CT forpre-CRT stageIV patients

PET interpretationblinded to clinicalinformation but notCT images

Pre-CRT PET:Distant metastases:sensitivity ¼ 78%,specificity ¼ 99%, PPV ¼ 56%,NPV ¼ 100%, accuracy ¼ 94%Liver: sensitivity ¼ 100%,specificity ¼ 99%, PPV ¼ 88%,NPV ¼ 100%, accuracy ¼ 100%Lung: sensitivity ¼ 80%,specificity ¼ 100%, PPV ¼ 100%,NPV ¼ 99%, accuracy ¼ 100%

Post-CRT PET:Distant metastases:sensitivity ¼ 39%,specificity ¼ 100%, PPV ¼ 88%,NPV ¼ 99%, accuracy ¼ 77%Liver: sensitivity ¼ 71%,specificity ¼ 100%, PPV ¼ 100%,NPV ¼ 98%, accuracy ¼ 85%Lung: sensitivity ¼ 40%,specificity ¼ 99%, PPV ¼ 67%,NPV ¼ 97%, accuracy ¼ 89%

Baseline PET canreliably detectmetastatic disease inliver and lung.

[12] To evaluate theimpact ofFDG-PET for thepreoperativedetection oflymph nodemetastasis andassociatedlocations, inpatients withdiagnosed locallyadvanced and/orpara-aortic

53 FDG-PET fromupper portionof the abdomento pelvis

Histopathology CT Radiologists wereblindedof the clinical findings

PET primary tumours andlymph node metastasis:N1: sensitivity ¼ 52.2%,specificity ¼ 87.5%,accuracy ¼ 70.2%, PPV ¼ 80.0%,NPV ¼ 65.6%N2e3: sensitivity ¼ 75.0%,specificity ¼ 94.4%,accuracy ¼ 89.6%, PPV ¼ 81.1%,NPV ¼ 91.9%N4: sensitivity ¼ 100.0%,specificity ¼ 100.0%,accuracy ¼ 100.0%,

Although FDG-PET ismarkedly moresensitive than CT forthe detection of N4lymph nodeinvolvement, thenumber of metastaticlymph nodes isdifficult to determine.

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lymph nodemetastaticcolorectaladenocarcinoma,as determined byCT findings,compared withpathological andCT findings

PPV ¼ 100.0%, NPV ¼ 100.0%CT primary tumours and lymphnode metastasis:N1: sensitivity ¼ 91.3%,specificity ¼ 41.6%,accuracy ¼ 65.9%, PPV ¼ 60.0%,NPV ¼ 83.3%N2e3: sensitivity ¼ 91.7%,specificity ¼ 72.2%,accuracy ¼ 77.1%, PPV ¼ 52.3%,NPV ¼ 96.3%N4: sensitivity ¼ 100.0%,specificity ¼ 17.6%,accuracy ¼ 41.7%, PPV ¼ 33.3%,NPV ¼ 100.0%

Treatment response[19] To evaluate

FDG-PET forearly evaluationof the responseto palliativechemotherapyand forprediction of thelong-termoutcome inpatients withmetastatic CRC

51 FDG-PETincluding trunkand neck

Histopathologyor clinicalfollow-up

None Pathologist blinded toclinical and PETfindings

Radiological group: Meanbaseline SUV for responderswas 5.6 (95% CI 4.4e6.8)compared with non-responders7.4 (95% CI 6.3e8.5) withP-value ¼ 0.02PET group: Mean baseline SUVfor responders was 6.1 (95% CI4.9e7.1) compared with 7.3(95% CI 6.1e8.5) withP-value ¼ 0.11Follow-up and survival:Median follow-up time was 19months. 1 year survival rates forPET responders was 78% and fornon-responders was 57%.

Although metabolicresponse assessed byFDG-PET reflectsradiological tumourvolume changes, thesensitivity andspecificity are too lowto support the routineuse of PET inmetastatic CRC.Furthermore, PETfailed to reflect long-term outcome andcan, thus, not be usedas surrogate end pointfor hard end pointbenefit.

[22] To monitor PETfindings duringneoadjuvant CRTand to correlateSUV changes andpathologicalresponse

33 FDG-PET beforeand 12 daysafter initiationof CRT

Histopathology None Pathologist blinded toclinical and PETfindings

The cut-off point value of themean decrease in SUV �52%yielded sensitivity andspecificity of 100%Significant correlation betweenpathological tumour regressiongrade and early SUV changes(P < 0.0001)

Early PET can predictpathological responseto neoadjuvant CRT.

[20] To assess theprognostic valueof PET carried outat restaging afterneoadjuvant CRT

88 FDG-PET 6e7weeks afterneoadjuvantCRT

Histopathology None NR Prediction of downstagingafter CRT:Sensitivity ¼ 61%,specificity ¼ 74%,accuracy ¼ 70%

Prediction ofdownstaging by post-CRT PET was notabsolute but PET incombination withpathological


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evaluation canidentify a subgroup ofpatients with morefavourable prognosis.

[21] To determine theprognostic valueof the degree ofchange intumour on PETinduced byneoadjuvant CRT

34 FDG-PET beforeand afterneoadjuvantCRT

Histopathology None NR PET indicated completeresponse in 17 of 30 patientsbut only 5 of these patients hadpathological absence of tumour.PET response was significantlyassociated with overall survivaland progression-free survival(P < 0.0001).

Complete responsewith PET does notindicate completepathological responsein most cases.Qualitative analysis ofPET can provideprognosticinformation.

[24] To evaluatesequential PET/CT comparedwithconventionalimaging topredict responseto neoadjuvantCRT

48 FDG-PET/CTfrom skull toupper legs

Histopathology None PET/CT interpretationblinded tohistopathologicalanalysis

Using SUV maximum decreasecut-off point of 66.2%:sensitivity ¼ 81%,specificity ¼ 79%, PPV ¼ 77%,NPV ¼ 89%, accuracy ¼ 80%

PET is potentiallyuseful asa complementarydiagnostic andprognostic procedureto assess treatmentresponse. Suggestreserving forprospectivecontrolled studies atthis stage of clinicalresearch.

[25] To investigatethe ability of PET/CT to predictpathologicalresponse toneoadjuvant CRT

30 FDG-PET/CTfrom skull baseto proximalthigh

Histopathology None Pathologist blindedto PET/CT results

Sensitivity ¼ 45%,specificity ¼ 75%, PPV ¼ 83%,NPV ¼ 33%, accuracy ¼ 53%

PET/CT performed 7weeks aftercompletion of CRTcannot predictcomplete pathologicalresponse or extent ofresidual disease.

[23] To determine theaccuracy of PETscans to detectresidual viableCRC liver aftera significantresponse tosystemicchemotherapy

138 FDG-PET Histopathology None NR PET within 4 weeks ofchemotherapy:Sensitivity ¼ 89.9% (95% CI83.3e94.5%), specificity¼ 22.2%(95% CI 2.8e60.0%), PPV¼ 94.3%(95% CI 88.6e97.7%),NPV ¼ 13.3% (95% CI1.7e40.5%), accuracy ¼ 85.5%(95% CI 78.5e90.9)

PET within 4 weeks ofchemotherapy is nota useful test forevaluation ofcolorectal hepaticmetastases. The highrate of false-negativeresults is probablydue to metabolicinhibition caused bychemotherapeuticdrugs. Werecommend that

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physicians not usePET in patientsrecently completingchemotherapy; theyshould undergo theappropriateoncological hepaticoperation based onthe high probability ofviable malignantdisease.

Recurrence[37] To evaluate PET

andintraoperativegamma probe forthe detection ofsuspectedrecurrent CRC

21 FDG-PET/CT,scull base toproximalfemoral region

Histopathology Intraoperativegamma probe

NR PET: sensitivity ¼ 84%,specificity ¼ 31%Intraoperative gamma probe:sensitivity ¼ 95%,specificity ¼ 38%

PET andintraoperative gammaprobe potentiallyhelpful to locate anddetermine extent oftumour recurrence.Intraoperative gammaprobe more sensitivein detecting extent ofabdominal and pelvicrecurrence but PETmore sensitive indetecting livermetastases.

[24] To assess thecontribution ofsystematic PET tothe detection andtreatment of CRCrecurrence aftercurative surgeryin patients athigh risk ofrecurrence

130 FDG-PET 9 and15 months aftersurgery, plusconventionalwork-up

Histopathology,clinical follow-up

Conventionalwork-up

PET interpretationblinded to CT, but notpatient history orother conventionalwork-up findings

Time from baseline untildetection of recurrence shorterwith PET than conventionalwork-up alone (12.1 versus15.4 months; P ¼ 0.01)PET: sensitivity ¼ 96%,specificity ¼ 92%, PPV ¼ 89%,NPV ¼ 97%Conventional work-up alone:sensitivity ¼ 91%, spec ¼ 93%,PPV ¼ 88.6%, NPV ¼ 95%

Regular PETmonitoring may leadto earlier detection ofrecurrence andinfluence treatmentstrategies.

[31] To evaluate theaccuracy ofintegrated PET/CT using FDGwith intravenouscontrast for thedepiction ofsuspectedrecurrent CRCand to assess theimpact of PET/

170 Whole bodyFDG-PET/CTscanning frommeatus of theear to the mid-thigh

Histopathology,radiologicalimaging andclinical follow-up

CT Radiologist wereblinded to imagingresults and otherclinical data

Patient-based diagnosticresults:CT alone: sensitivity ¼ 79.7%(95% CI 70.5e88.9%),specificity ¼ 93.8% (95% CI89.0e98.6%), PPV ¼ 90.8% (95%CI 83.8e97.8%), NPV ¼ 85.7%(95% CI 78.8e92.7%),accuracy ¼ 87.6% (82.7e92.6%)PET/non-contrast-enhanced CT:sensitivity ¼ 89.2% (95% CI

Integrated PET/contrast-enhanced CTis an accuratemodality for assessingCRC recurrence andled to changes in thesubsequent therapy.


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contrast-enhanced CTfindings onclinicalmanagementcompared withPET/non-contrast-enhanced CT andCT component

82.1e96.3%), specificity¼ 94.8%(95% CI 90.4e99.2%),PPV ¼ 93.0% (95% CI87.1e98.9%), NPV ¼ 91.9% (95%CI 86.5e97.3%),accuracy ¼ 92.4% (88.4e96.4%)PET/contrast-enhanced CT:sensitivity ¼ 93.2% (95% CI87.5e98.9%), specificity¼ 95.8%(95% CI 91.8e99.8%),PPV ¼ 94.5% (95% CI89.3e99.7%), NPV ¼ 94.8% (95%CI 90.4e99.2%),accuracy ¼ 94.7% (91.3e98.1%)Change in management:CT alone: 12/170 (7%)PET/contrast-enhanced CT: 64/170 (38%)PET/non-contrast-enhanced CT:4/170 (2%)

[32] To examine thesensitivity andspecificity of CT/MRI serial reviewcompared with18FDG-PET/CTscanning tooptimise CRCfollow-up

50 FDG-PET/CT Histopathologyand clinicalfollow-up

CT/MRI Radiologist wereblinded to all imagingreport

PET: sensitivity ¼ 83e87%,specificity ¼ 93e96%,accuracy ¼ 88e92%CT/MRI: sensitivity ¼ 83%,specificity ¼ 89e100%,accuracy ¼ 86e92%

With suspectedrecurrence, a serialimaging review isrecommended withcareful correlation ofsuspicious findingswith previous studies.FDG-PET/CT imagingwas useful whenfindings remainequivocal after serialimaging review forCRC recurrence.

Liver metastastases[27] To investigate

the value of theaddition ofFDG-PET toconventionalCT-baseddiagnosticimaging inpatientsconsideredeligible for

150 Whole bodyFDG-PETscanning


CT NR Significant proportion (45%) ofpatients in control groupunderwent futile laparotomycompared with 28% in theexperimental group(P-value ¼ 0.042).Relative risk reduction was 38%(95% CI 4e60%) with anabsolute difference of 17%means that 6 patients need to

Preoperative FDG-PETin patients with CRCliver metastasesconsidered resectablebased on CT reducesthe number of futilelaparotomies due tounexpectedunresectable disease.The finding ofextrahepatic disease

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hepatic surgeryof colorectal livermetastases

undergo FDG-PET to avoid 1futile laparatomy

on PET and PETnegative liver lesionsshould not bedisregarded.

[35] To evaluate PETfor theassessment oflocal control andsystemic diseasein patients withsuspectedtumourprogression afterlaser-inducedthermotherapyof CRC livermetastases

21 FDG-PET fromskull to upperlegs

Histopathology,imaging,clinical follow-up

None PET interpretationblinded to otherimaging methods andclinical information

PET detection of residualtumour:Visual diagnosis (overall,including immediate, short-term and long-term follow-up):sensitivity ¼ 97%,specificity ¼ 96%, PPV ¼ 97%,NPV ¼ 96%, accuracy ¼ 96%T/N, SUVmax: sensitivity ¼ 97%,specificity ¼ 92%, PPV ¼ 93%,NPV ¼ 96%, accuracy ¼ 94%

PET is a reliable toolfor the evaluation oflocal control anddetection ofunexpectedextrahepatic diseasein patients withsuspected recurrenceafter laser-inducedthermotherapy of CRCliver metastases.

[28] To compare PET/CT, MRI, PET andCT in thedetection of livermetastases andextrahepatictumour

35 PET/CT Ultrasoundmorphology orhistopathology

MRI, CT, PETalone

Interpretation blindedto results of otherimaging studies

Detection of liver metastases(analysis by lesion):PET/CT: sensitivity ¼ 66%,specificity ¼ 99%, PPV ¼ 98%,NPV ¼ 76%, accuracy ¼ 83%CT: sensitivity ¼ 89%,specificity ¼ 67%, PPV ¼ 72%,NPV ¼ 86%, accuracy ¼ 77%PET: sensitivity ¼ 54%,specificity ¼ 99%, PPV ¼ 97%,NPV ¼ 69%, accuracy ¼ 77%MRI: sensitivity ¼ 82%,specificity ¼ 81%, PPV ¼ 81%,NPV ¼ 82%, accuracy ¼ 82%Detection of extrahepatictumour (analysis by patient):PET/CT: sensitivity ¼ 84%,specificity ¼ 96%CT: sensitivity ¼ 59%,specificity ¼ 87%

CT and MRI are moresensitive but lessspecific than PET indetection of livermetastases. PET/CTdetected morepatients withextrahepatic tumourthan CT alone.

[34] To examine theeffect ofneoadjuvantchemotherapyfor CRC livermetastases on CTand PET/CTfindings and todetermine the

75 PET/CT fromhead to pelvicfloor

Histopathology CT NR Identification of livermetastases in patients withoutneoadjuvant chemotherapy(n ¼ 27):PET: sensitivity ¼ 93.3%CT: sensitivity ¼ 87.5%Identification of livermetastases in patients withneoadjuvant chemotherapy

Sensitivity of PET indetecting livermetastases decreasesfollowingneoadjuvantchemotherapy.Patients should bestaged with PET/CTbefore and after


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role of theseimagingmodalities

(n ¼ 48):PET: sensitivity ¼ 49%,specificity ¼ 83.3%CT: sensitivity ¼ 65.3%,specificity ¼ 75%

neoadjuvant therapy.CT is more sensitivethan PET in detectingmetastases followingneoadjuvant therapy.

[36] To evaluate theaccuracy ofpreoperative andintraoperativePET and CTimaging ofpatients withCRC livermetastases

131 FDG-PET Histopathology,intraoperativeultrasound asback-up

CT NR PET and CT missed most lesionssmaller than 10 mm and 25% oflesions between 10 and 20 mm.PET: sensitivity ¼ 98%,specificity ¼ 100%CT: sensitivity ¼ 99%,specificity ¼ 0% (0/3)Extrahepatic intra-abdominaldisease was found in 10patients. PET missed 4 patientsand CT missed 8 patients.

CT and PET havea similar diagnosticyield for identificationof liver metastases butboth are inadequateto detect smalllesions.Frequency ofunexpected findingsat laparotomy isrelatively low whenusing CT and PET inthe preoperativework-up.

[29] To evaluateFDG-PET inpatients beingconsidered forresection ofcolorectal livermetastases andwhether PETalters treatmentmanagement

31 FDG-PET Surgicalexploration,histopathology,clinicalradiologicalfollow-up

CT NR PET sensitivity:liver metastases ¼ 96%,pulmonary metasases ¼ 100%extrapulmonary/extrahepatic ¼ 100%CT sensitivity:liver metastases ¼ 70%pulmonary ¼ 83%extrapulmonary/extrahepatic ¼ 20%PET results altered clinicalmanagement in 9 patients(29%)

FDG-PET offers highersensitivity than CT inthe detection of CRCsecondary depositsand has a majorinfluence on theselection of patientsfor resection ofcolorectal livermetastases.

[33] To investigateFDG-PET/CT asa preoperativeplanning tool fordissecting liverlesions inpatients with andwithoutpreoperativechemotherapy.

74 FDG-PET/CT Histopathology None Nuclear medicinephysicians were notblinded to previouspatient imagingresults

21 patients with preoperativechemotherapy:accurate scans in 6 patients(28.6%), false-negative scans in11 patients (52.4%), false-positive in 4 patients (19.0%)53 patients withoutpreoperative chemotherapy:accurate scans in 28 patients(52.8%), false-negative scansin 18 patients (34.0%),false-positive in 7 patients(13.2%)

Preoperativeassessment with FDG-PET/CT is not usefulfor hepatic colorectalmetastases,particularly whenpreoperativechemotherapy isused, with a trendtowardsunderestimation oflesions.

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27 patients with necrosis:accurate scans in 11 patients(40.7%), false-negative scans in10 patients (37.0%), false-positive scans in 6 patients(22.2%)47 patients without necrosis:accurate scans in 22 patients(46.8%), false-negative scans in20 patients (42.6), false-positivescans in 5 patients (10.6%)

[30] To assess theimpact of PET/CTon thetherapeuticstrategy of thepatience withCRC metastasis

15 Whole bodyFDG-PET/CTscanning


CT NR Liver metastasis:PET/CT: sensitivity ¼ 100%,specificity ¼ 100%CT: sensitivity ¼ 80%,specificity ¼ 100%Statistical significant differencewith P-value ¼ 0.0009

PET/CT is superior tocontrast-enhanced CTfor the detection ofthe metastatic lesionsof CRC, and isa valuable tool to helpselect the correcttherapeutic strategies

CI, confidence interval; CRT, chemoradiotherapy; CT, computed tomography; FDG-PET, fluoro-2-deoxy-D-glucose positron emission tomography; MRI, magnetic resonance imaging;NPV, negative predictive value; NR, not reported; PPV, positive predictive value; SUV, standard uptake value.

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