Enucleation of Tumor Versus Partial Nephrectomy as Conservative Treatment of Renal Cell Carcinoma Richard Stephens, MD, and Sam D. Graham Jr, MD

In patients with renal insufficiency, solitary kidney, or bilateral renal malignancies, conservative surgery for renal cell carcinoma has been suggested. The authors treated 17 such patients with either enucleation of tumor or partial nephrectomy. Overall survival from disease in this series was 58.8%. Seventy percent of patients undergoing enucleation and 42.9% undergoing partial nephrectomy survived with a mean follow-up period of 5 years. Survival or local recurrence rate after enucleative surgery is an effective treatment of renal carcinoma in selected patients, and despite concerns about tumor invasion of the pseudocapsule, the clinical data do not indicate any difference in survival. There was no significant difference between enucleation of tumor and partial nephrectomy regarding morbidity, mortality, or recurrence rate. Cancer 65:2663-2667, 1990.

T WAS DEMONSTRATED in 1969 by Robson and asso- I ciates that radical nephrectomy improved survival over simple nephrectomy.' The 5-year survival rate after radical nephrectomy in patients with Stage I, 11, and 111 disease has been noted to be 65% to 80%, 42% to 64%, and 42% to 5 1 %, respectively. 's2 Under ideal circumstances, the goal of the surgeon should be radical resection of the tumor in its entirety, including the kidney and its perinephric tissue. In certain clinical settings, the surgical approach must be altered to preserve functioning renal parenchyma. Indications for conservative surgery include bilateral renal cell carcinoma (synchronous and asynchronous) and uni- lateral renal cell carcinoma in a patient with a solitary or sole functioning kidney or with renal insufficiency. There has been considerable controversy regarding the appro- priate technique for conservative treatment of renal cell carcinoma with some proponents advocating formal par- tial nephrect~rny,~,~ whereas others have advocated enu- cleation of turn or^.^-^ The proponents of formal partial nephrectomy argue that the risk of enucleation leaving tumor in the capsule would be a contraindication to enu- ~ l e a t i o n . ~ , ~ This study reviews 17 consecutive patients treated in a 10-year period with either formal partial ne- phrectomy or enucleation.

From the Department of Surgery, Section of Urology, Emory Uni-

Address for reprints: Sam D. Graham, Jr, MD, Section of Urology,

Accepted for publication December 19, 1989.

versity School of Medicine, Atlanta, Georgia.

1365 Clifton Road, Atlanta, GA 30322.

Materials and Methods

Seventeen patients treated within the Emory University Hospital system (Atlanta, GA) underwent conservative surgical treatment for renal cell carcinoma during a 10- year period (1974-1984) (Tables 1 and 2). All patients' charts were reviewed for pathologic stage, early and late morbidity, and survival. Ten of these patients underwent enucleation and seven underwent a formal partial (guil- lotine) nephrectomy. All patients undergoing partial ne- phrectomy had polar lesions, whereas enucleations were performed primarily for multiple tumors, mid-kidney tu- mors, or for other reasons where wide margins were not possible.

Results

Demographics

Of the 17 patients, there were seven women and ten men. The patients ranged in age between 36 and 76 years (average, 59.1 years). Seven patients had contralateral be- nign disease (Group A) whereas ten had contralateral ma- lignancies (Group B). Two patients in Group A had had no prior nephrectomy, but had conservative therapy for renal insufficiency. Within Group B, six had synchronous and four had asynchronous tumors. Of the six patients with synchronous disease, three patients underwent si- multaneous procedures on both kidneys whereas three had staged procedures. All patients were followed for a time period of 27 to 112 months (average, 59.8 months).

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2664 CANCER June 15 1990 Vol. 65

Pathologic Findings

Of the 17 patients, 12 of 17 had Stage I and five of 17 had Stage I1 or 111 tumors. Three of seven (43%) patients undergoing partial nephrectomy and two of ten (20%) patients in the enucleation group had higher stage tumors (P = NS). Of the ten patients with contralateral tumors, nine of ten had Stage I disease and one of ten had Stage Ill disease. Maximal tumor diameter was 2.7 to 10 cm (mean, 5.5 cm) in the enucleation group and 2 to 10 cm (mean, 5.8 cm) in the partial nephrectomy group (P = NS).

Survival

The results are shown on Tables 1 through 4. The over- all survival free of disease was 58.8% with a mean follow- up of 59.8 months (5 years). The ten patients undergoing enucleative surgery had a 70% (seven of ten) survival rate free of disease during a mean follow-up of 59.3 months (4.9 years); the seven patients who were treated with partial nephrectomy had a survival rate free of disease of 42.9% (three of seven) during a mean follow-up of 60.6 months (5 years). This did not represent a statistically significant difference in survival between the two groups.

In patients with contralateral benign disease, the sur- vival free of disease was 57.1% with a mean follow-up of 59 months. For those ten patients with contralateral renal cell carcinoma, the survival free of disease was 60% with

a mean follow-up of 60.4 months. This was not a statis- tically significant difference.

In our six patients with synchronous tumors, the sur- vival free of disease was 67% with a mean follow-up of 67.2 months. The four patients with asynchronous tumors had a survival of 50% with a mean follow-up of only 41.5 months after the second surgery. This difference in sur- vival was not statistically significant. In our small number of patients with asynchronous tumors, a longer time pe- riod between sequential tumors tended to be associated with a poor prognosis, even though these patients were relatively young when the first tumor was diagnosed. Overall there were five patients who developed systemic recurrence (three in the partial nephrectomy and two in the enucleation group). There were no local recurrences.

Morbidity

The serum creatinine levels for the preoperative and postoperative period (after stabilization of renal function) are shown in Table 3. This table does not include those patients with synchronous renal cell carcinoma who un- derwent surgery for the second tumor simultaneously or within a 3-month period from the first surgery, as the degree of impact of the particular conservative surgery on renal function could not be accurately assessed in these patients. There was no significant difference in the two groups regarding early or late changes from the preoper- ative treatment.

TABLE 1. Enucleation

Interval Surgery for synchronous Reason for between

Patient Age Reason for prior renal conservative sequential Size of largest Stage FOIIOW-UP no. (yr) Sex nephrectomy adenocarcinoma surgery tumors (mo) tumor (cm) (initial/last) NED (mo)

1 74 M R Conservative Bilateral 0 4.0 111 + 75 L Radical RCC

2 48 F TB Prior 10.0 111 + 112

3 76 M Chronic Pyelo Prior 9.5

4 63 M R Conservative Bilateral 0 5.5 I/IV

nephrectomy

nephrectomy 62

80

6 64 F Stones Prior 8.0 11/11 + 15 nephrectorny

13 54 F R Conservative Bilateral 0 4.3 I/I + 38

14 61 F R Conservative Bilateral N/A 3.5 I/I + 27

15 68 M Renal 4.4 I/I + 28

II/IV -

- L Radical RCC (died)

L Radical PCC

L Radical tumor*

insufficiency (died) Renal

16 63 M adenocarcinoma Prior 26 3.0 I/I +- 53 Stage I nephrectomy

17 49 M R Conservative Bilateral 0 2.7 I/I + 42 L Radical RCC

TB: tuberculosis; R: right; L left; Pyelo: pyelonephritis; RCC: renal * L angiomyolipoma. cell carcinoma; N/A: not available; NED no evidence of disease.

No. 12 ENUCLEATION OF TUMOR IN RENAL CELL CA - Stephens and Graham 2665

TABLE 2. Partial Nephrectomy

Surgery for Interval synchronous Reason for between

Patient Age Reason for prior renal conservative sequential Size of largest Stage FOIIOW-UP no. (yr) Sex nephrectomy adenocarcinoma surgery tumors (mo) tumor (cm) (initial/last) NED (mo)

90 5 58 F R Conservative Bilateral 0 6.7 II/IV -

7 76 M Bilateral Bilateral 0 3.7 I/I + 93 L Radical RCC (died)

conservative RCC 5.1 8 49 M Chronic Pyelo Prior 9.2 III/III + 80

nephrectomy (died) Renal

Stage I nephrectomy Renal

Stage I nephrectomy (died)

9 42 M adenocarcinoma Prior 45 6.5 I/I + 57

10 36 F adenocarcinoma Prior I25 10 I/IV - 35

11 69 M Renal 2 11/11 + 28 insufficiency

Renal

Stage I nephrectomy 41 12 55 F adenocarcinoma Prior 63 3.5 I/IV -

Pyelo: pyelonephritis; RCC renal cell carcinoma; R right; L left; NED no evidence of disease.

Discussion and possible transplantation) to partial nephrectomy. The

Since the report by Robson et al. of increased survival with radical versus simple nephrectomy, the standard method of treatment of renal cell carcinoma has been radical nephrectomy with removal of the kidney, peri- nephric fat, and Gerota's fascia.' Some patients, however, are not candidates for radical nephrectomy due either to an absolute or functional loss of the contralateral renal unit. This group includes patients who have had prior contralateral nephrectomy for benign or malignant dis- ease, patients with a congenitally absent kidney, and pa- tients with insufficient renal function secondary to chronic pyelonephritis, atherosclerosis, or other renal insult, and patients with bilateral simultaneous adenocarcinoma.'-' '

Suggested therapy for patients with a tumor in a solitary kidney has ranged from radical nephrectomy (with dialysis

TABLE 3. Renal Insufficiency in Patients Undergoing Conservative Surgery Only: Partial Nephrectomy Versus Enucleation

Creatinine

Patient Preoperative Postoperative

Partial 8 9

10 I 1 12

Enucleation 2 3 6

15 16

1.2 1.2 1.2 0.8 1.2

1.1 1.9 1.3 2.2 2.1

15-2.8 1.5 1.4 1 .o 1.7

1 .o 9.5-2.3

1.2 2.1 2.2

latter procedure can be performed in vivo, ex vivo, and can be either a guillotine or wedge resection, taking a margin of normal renal tissue, or enucleation of the tumor from its pseudocapsule.

If partial nephrectomy is considered, it is very important that a complete preoperative assessment be performed in order to be prepared for appropriate surgical intervention. The extent of the disease must be documented by com- puted tomography (CT) scan and possibly magnetic res- onance imaging (MRI) to rule out vena caval thrombus. Angiography is helpful in determining the vascular anat- omy of the affected kidney. The patient should be advised in advance that even though the plan is to preserve the kidney, there may arise a circumstance necessitating re- moval of the kidney, or the patient may require temporary or permanent dialysis due to acute chronic renal failure.

During the surgical procedure, it is imperative to work quickly and to avoid warm ischemia as much as possible. If a formal partial nephrectomy or enucleation will involve temporary cross clamping of the renal artery, it is nec-

TABLE 4. Enucleation for Renal Adenocarcinoma

Tumor Follow-up in size cm

Patients yr (mean) (mean) '% NED Reference

5 0.75-5 (2.75) 1.5-5 (3.5) 100 22 7 0.5-7 (3.7) 2-6.5 (4.6) 100 25

33 0.75-13 (3.8) 1-10 (3.6) 85 26 10 2.3-9.3 (4.9) 1-10 (4.5) 70 current study

NED: no evidence of disease.

2666 CANCER June 15 1990 Vol. 65

essary to institute a diuresis (25 g mannitol) and use saline slush to reduce the core temperature of the kidney, thereby preventing warm ischemia. One of the advantages of enu- cleation, especially of small tumors, is the ability to per- form the operation without vascular occlusion.

In a report of 6 1 cases by Jacobs et al., ten patients treated by radical nephrectomy and hemodialysis or transplantation had only a 40% survival at the time of report; the longest survival on chronic dialysis in six pa- tients was 42 months.” This decrease in survival, however, may be due to patient selection with the higher local stages being treated in this manner. Spees et al. showed a 50% tumor-free survival at 4 to 9 years’ follow-up in patients in whom an asymptomatic renal cell carcinoma was dis- covered incidentally during a pretransplant nephrec- tomy. Other transplantation studies have shown an in- crease in survival rate in patients with asymptomatic renal cell carcinoma and in patients in whom there was a longer waiting period between nephrectomy and transplanta- tion. l4

In some cases conservative surgery is not possible be- cause the renal unit is so extensively involved with tumor; under these circumstances, total nephrectomy has been recommended in patients with low-stage tumors. In pa- tients with limited-functioning renal tissue and less ex- tensively involved kidney, aggressive treatment consisting of radical nephrectomy with chronic hemodialysis or transplantation has been questioned.” The disadvantages include the inherent risks and complications of dialysis and transplantation, an altered quality of life for the pa- tient with life-long dependence on drugs and artificial life supports, and an increase in medical expenditures. The age at presentation of many of these patients with renal cell carcinoma disqualifies them as suitable candidates for transplantation. The mortality from hemodialysis after total radical nephrectomy is similar to that associated with hemodialysis in other high-risk group^.'^,'^

Many studies have shown the success of partial ne- phrectomy for treatment of renal cell carcinoma in pa- tients with limited-functioning renal tissue. With partial nephrectomy, the malignancy may be removed with its tumor-free margin and sometimes with its attached peri- nephric fascia; however, valuable functioning renal tissue is lost, either by excision of tumor margin or by infarction secondary to hemostatic closure or secondary to transec- tion of parenchyma vessels. Ischemic damage secondary to intraoperative clamping of the artery is usually only temporary but can complicate the postoperative care.

Partial nephrectomy has been recently reported in nu- merous studies and reviews of the literature to have sur- vival rates ranging from 50% to 100% at the time of re-

ese rates overall compare favorably to the survival rates after radical nephrectomy for low- stage tumors. With partial nephrectomy, tumor excision

port.3,9, I I . I 2,15,17-26 Th

crosses normal renal tissue and the segmental arteries, at times making hemostasis difficult.

Bench surgery, even though it offers a more precise and hemostatic resection of the tumor, requires more com- plicated surgery with prolonged anesthesia time. 12,17 Bench surgery has also been associated with a much higher com- plication rate.18

Enucleative surgery has been presented as an alternative to partial nephre~tomy.~,~ The surgical technique involves exposure of the vascular pedicle, after which blunt enu- cleation may be performed quickly, usually requiring only digital compression of the parenchymal vessels. The ad- vantages of enucleative surgery include minimal blood loss and minimal loss of functioning renal tissue, and ability to treat multiple tumors in one kidney. Although guillotine partial nephrectomy is usually only possible in either upper or lower pole tumors, enucleation is not lim- ited by the position of the tumor. In reviewing 45 patients with carcinoma in a solitary kidney, Grabstald and Aviles noted that 18% were not situated near either pole.20

Some authors are skeptical of enucleative surgery in that it conflicts with the postulates of radical removal of a neoplasm. Rosenthal et al. and Marshall et al. showed in the enucleation of tumors, there were residual tumor cells with the pseudo~apsule.~~~ Graham and Glenn,’ Ca- rini et a1.,6 and Novick et al.,7 however, have shown sur- vival statistics equivalent to those of most partial ne- phrectomy series. Critics of enucleation have also ques- tioned the efficacy of enucleation in larger tumors; however, in this series, size of the tumor did not correlate with survival in the enucleation population.

In none of our patients undergoing enucleation was the tumor locally recurrent. Furthermore, from our study, there is no indication that partial nephrectomy improves the survival from tumors greater than 5 to 6 cm. Our study agrees with other recently published studies dem- onstrating good survival among patients undergoing enu- cleative surgery (Table 4).5-7

Our group of patients undergoing formal partial ne- phrectomy had a lower survival rate than one might ex- pect; this could be due to the fact that three of seven patients had Stage 11-111 tumors versus two of ten patients undergoing enucleation.

In his review of patients from 19 10 to 1974, Wickham suggested that patients with benign contralateral disease have a greater survival than those patients with contra- lateral renal cell carcin~ma.’~ Review of his cases, how- ever, reveals that only nine of 26 patients with contralat- era1 carcinoma underwent surgical treatment; whereas, 22 of 25 patients with benign contralateral disease un- derwent surgery. Recent studies, including our series of patients, have shown that if conservative surgery is per- formed, survival rates are similar despite the fate of the contralateral kidney.’ Earlier reports indicated a worse

No. 12 ENUCLEATION OF TUMOR IN RENAL CELL CA - Stephens and Graham 2667

prognosis for sequential bilateral tumors with a shorter interval between tumor diagnosis in the two kidneys. ” Marberger et al. found no prognostic significance in the time interval between discovery of asynchronous tumors and no significance difference in the survival of asyn- chronous and synchronous tumors.’8 Our study confirms that synchronous tumors do not have the poor prognosis with which they were associated in the past.

Although the groups are relatively small, this study in- dicates that actual survival and recurrence in patients un- dergoing enucleation of renal cell carcinoma may be comparable to formal partial nephrectomy. Concerns re- garding residual tumor may be overstated and in this series do not appear to be clinically significant. Recently, we have utilized the argon beam coagulator (CR Bard Inc., Englewood, CO) for both hemostasis and possible tumor stasis in the capsule. Another alternative would be the use of the Nd:YAG laser for the same purpose. However, this and other series of patients undergoing enucleation are small and it may be hazardous to draw long-term con- clusions at this time.

Our preference remains to obtain optimal surgical margins, yet enucleation is a good alternative in very se- lected patients. The best modality for treatment of renal carcinomas remains radical nephrectomy in all patients for whom this is feasible.

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