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Is Ipsilateral Adrenalectomy a Necessary Component of Radical Nephrectomy?
~~22-5347/95/1535-1415$03.00/0 THE JOURNAL OF UROLOGY copyright 0 1995 by AMERICAN UROLOCICAL ASSOCIATION, Lc.
Vol. 153, 1415-1417,May 1995 Prinfed in U S A .
IS IPSILATERAL ADRENALECTOMY A NECESSARY COMPONENT OF RADICAL NEPHRECTOMY? M. SHALEV, B. CIPOLLA, F. GUILLE, F. STAERMAN
AND
B. LOBEL*
From the Department of Urology, Hopital Pontchaillou, Rennes, France
ABSTRACT
Due to t h e increased use of modern imaging systems during the last few years, kidney tumors are often diagnosed at an earlier and less advanced stage. This fact implies a reevaluation of t h e operative technique of radical nephrectomy that was recommended 30 years ago. The ipsilateral adrenal involvement during radical nephrectomy for renal cell carcinoma is assessed and the necessity of its extirpation is discussed. Between September 1987 and September 1993, we performed 299 radical nephrectomies for renal cell carcinoma and removed 285 ipsilateral adrenal glands. Eleven adrenal glands (3.8%) were involved with the kidney tumor and 274 (96.2%) were free of disease. I n 7 of the adrenal gland involved cases (63.6%) the tumor invaded the gland by direct extension from the superior pole of the kidney. In the other 4 cases the ipsilateral adrenal gland was affected by a metastatic lesion. In all 11adrenal gland involved cases the tumors were at a n advanced stage (the lowest was stage pT3N1). Our results led us to recommend adrenalectomy during radical nephrectomy only when direct extension of the kidney tumor into the gland is suspected (upper pole or large tumors) or when the adrenal is the site of a single metastasis. Macroscopically normal adrenal glands at radical nephrectomy should not be routinely extirpated. Metastatic renal cell carcinoma (not by contiguity) in the ipsilateral adrenal gland should be regarded as a stage M+ (distant metastasis) tumor. KEYWORDS:adrenal glands; adrenalectomy; kidney neoplasms; nephrectomy;carcinoma, renal cell
In 1963 Robson recommended radical nephrectomy including ipsilateral adrenalectomy as the treatment of choice for renal cell Carcinoma.’ This operation was universally accepted because of its relative simplicity and adherence to the surgical oncology principle of a “wide margin beyond the malignancy.” At that time adrenal involvement in renal cell carcinoma was estimated to be present in 5 to 10% of the cases. Due to the increased use of ultrasound and computerized tomography (CT) during the last decade, the incidence of small, low stage tumors has grown considerably. This high incidence of accidentally discovered low stage renal cell carcinoma gave rise to new ideas about a more conservative surgical approach. It was suggested that ipsilateral adrenalectomy should be performed only if the tumor was in the upper pole of the kidney, or when there was preoperative or intraoperative evidence of adrenal metastasis. However, some urologists still recommend adrenalectomy in patients undergoing radical nephrectomy. We assess the ipsilateral adrenal involvement in renal cell carcinoma to determine whether routine ipsilateral adrenalectomy during radical nephrectomy is still required.
ian vessels were dissected and tied. Disease was staged according to the 1992 TNM classification. To examine the possibility of predicting adrenal involvement in renal cell carcinoma in relation to stage or lymph node involvement, the likelihood ratio test was performed (Bayes’ theorem1.2 To test the likelihood ratio for adrenal involvement in relation to advanced T stage, patients were divided into 2 groups: group 1-stages T1 and T2 disease, and group 2-stages T3 and T4 cancer. Regarding lymph node involvement, the patients were divided into those with positive and negative lymph nodes. The test was not considered predictive of adrenal involvement for likelihood ratio values of less than 5 , while values of 5 to 10 were considered good prediction (but insufficient as a solitary test) and those greater than 10 as excellent prediction. Likelihood ratio is calculated by the formula true positivdnumber of adrenal invo1vement:false-positivdnumberof nonadrenal involvement. RESULTS
Involvement of the ipsilateral adrenal gland in renal cell carcinoma was found in 11 of 285 patients (3.8%),including PATIENTS AND METHODS 3 women and 8 men (mean age 59.4 years, table 1). All Between September 1987 and September 1993, 299 pa- adrenal glands were reviewed by the pathologist and no tients with renal cell carcinoma were treated surgically. Rad- incidental tumors were found in this series. In 7 of the 11 ical nephrectomy with ipsilateral adrenalectomy was per- patients with adrenal involvement the tumor invaded the formed in 179 men and 106 women 35 to 85 years old (mean gland by direct extension from the upper pole. In the other 4 age 64.6 years). The operative technique consisted of removal patients the renal tumor was in the mid or lower portion of of the tumor en bloc together with the adipose capsule, prox- the kidney and extension to the adrenal gland was by distant imal third of the ureter and adrenal gland, according to the metastasis. The renal cell carcinoma measured 6 to 15 cm. in anatomical boundaries of Gerota’s fascia. In addition, re- largest diameter. The disease was stage pT3c in 3 patients gional lymph nodes were excised, and the spermatic or ovar- and stage pT4a in 2. In the latter 2 patients the tumor invaded the peritoneum in 1 and the liver in 1. Lymph node Accepted for publication September 23, 1994. * Requests for reprints: Department of Urolo Hopital Pontchail- metastases were found in all 11 patients (9 stage N2 and 2 stage Nl). Distant metastases were found in the lung of IOU, Rue Henri Le Guilloux, 35033 Rennes Ce%k, France. 1415
1416
ADRENALECTOMY DURING RADICAL NEPHRECTOMY TABLE1. Tumor stage, location, and mechanism of adrenal involvement in patients with adrenal metastases
Pt.-Sex -Age
Stage
Location of TumorlKidney
Diameter (cm.)
1-M-70 2-M-66 3 - F -85 4-M-72 5-M-53 6-M-54 7-M-42 8-M-39 9 - F -57 10-F -55 11 -M - 6 1
T3cN2Mo T3cN2Mo T3cN2Mo T3cNlMo T3cN2Mo T3cN2Mo T4ah'2Mo T3cN2M1 T4aN2M1 T3cNlMo T3cN2Mo
Lower pole& Lower poldrt. Upper pole and mid portiodrt. Upper poldrt. Upper pole and mid portiodrt. Lower poldrt. Upper poldt. Upper poldrt. Upper poldrt. Upper poldt. Lower pole and mid portiodrt.
7 6 12 14 15 12 15 15 9 11 13
patients 8 and 9. Adrenal metastases were identified by CT preoperatively in only patients 4 and 6. The excised ipsilateral adrenal glands were free of disease in 274 patients (96.2%). Of these patients 98 (35.7%) had stage pT3 and 4 (1.4%) had stage pT4 carcinoma, with lymph node involvement in 52 (18.9%). The likelihood ratio for adrenal involvement was 2.7 in relation to T stage and 5.2 in relation to lymph node involvement (N stage). Therefore, we assume that in the case of nodal metastases the likelihood of adrenal involvement is high. Nodal involvement seems to be far more predictive of adrenal involvement than local spread of the tumor (likelihood ratio 5.2 compared to 2.7 when T stage is concerned). DISCUSSION
Mechanism of Adrenal Involvement Metastases Metastases Contiguous Contiguous Contiguous Metastases Contiguous Contiguous Contiguous Contiguous Metastases
TABLE2 . Frequency of adrenal metastases in renal cell carcinoma after nephrectomy Reference
No. Pts
No. Adrenal Metastases (W)
88 4 (4.5) Robsong 58 6 (10) Angervall and Wahlqvist'" 429 5 (1.2) Hohenfellner and Zingg" 82 2 (2.4) Rnbey and Schellhammer12 138 8 (5.8) Winter et all3 111 3 (2.8) Jaschke et all4 72 4 (5.5) O'Brien and Lynch15 161 9 (5.6) Jaeger and Vahlensieck'6 119 6 (5) Haab et all7 156 12 (8.3) Saussine et all8 233 CoulangeIg.* 9 (3.9) 285 11 (3.8) Present study Totals 1,932 79 (4.08) * Comitd de Cancerologie de I'association Franqaise d'Urologie.
In 1963, when Robson described the surgical approach to radical nephrectomy,' renal cell carcinoma was diagnosed mostly by the appearance of clinical symptoms. All urological but when related t o the local stage of the tumor (T stage) it textbooks from that period described the classical triad of was only 2.7. In other words, adrenal involvement seems to flank pain, flank mass and hematuria as pathognomonic for depend more on the lymphatic spread than on the local T renal cell carcinoma. As a result of late diagnosis, most of the stage of the tumor but it should also be emphasized that to patients had large volume tumors and advanced stage dis- our knowledge adrenal involvement with renal cell carciease. Due to the increased use of ultrasound and CT during noma of less than 5 cm. has never been reported.17 Adrenalectomy during radical nephrectomy is also justified the last decade, there has been an increase in the incidence of small renal cell carcinoma detected at an early stage. This when it is the site of a solitary metastasis. A better prognosis tendency of early diagnosis led surgeons to consider kidney was reported (30% survival at 5 years) when solitary metassparing surgery when the tumors were small (mean 3.3 cm.) tases were removed,21*22an approach valid for the contralatera1 adrenal as well. and of low grade and ~ t a g e . 3 . ~ Is adrenalectomy justified when the adrenal is macroscopThe staging classification was also adjusted to this new approach, differentiating between stage T1 renal cell carci- ically normal? Winter et al, analyzing 138 radical nephrecnoma (a localized tumor up to 2.5 cm. in diameter that does tomies, found 8 patients (5.8%) with adrenal involvement, 3 not distort the calices and renal pelvis, in which case renal of whom (2.1%) had adrenal micrometastases that could not sparing surgery should be considered) and stage T2 disease be diagnosed preoperatively or intraoperatively.13 Based on (for which radical nephrectomy is still mandatory). Never- these findings, they concluded that ipsilateral adrenalectomy theless, the benefit of radical nephrectomy compared to sim- should be performed routinely to eliminate the potential miple nephrectomy considering the progression of the disease crometastases-bearing adrenal glands with the possibility of and survival rates has not yet been proved.5.6 Moreover, being cured. We do not agree with the concept that adrenal renal cell carcinoma is an unpredictable tumor. Metastases micrometastases are a local extension from the renal cell have been reported to appear as late as 13years after radical carcinoma. In fact, adrenal micrometastases, invading the nephrectomy and sometimes were dormant for as long as 35 gland lymphogenously or hematogenously, are rather the years when left untreated.7.8 expression of a systemic disease that should be a t a higher Despite the tendency to perform more conservative surgery stage in the TNM classification, that is stage pTxM+ instead during the last few years, urologists still perform ipsilateral of pT3a. Routine ipsilateral adrenalectomy for the presumed adrenalectomy during nephrectomy for renal cancer as a benefit of2.1% of the patients who at least theoretically have matter of routine. Adrenal involvement in radical nephrec- a systemic disease with multiple micrometastases is not justomy specimens has been reported to occur in 1.2 to 10% of tified in our opinion. the patients (mean 4.08%, table 2),9-19 and as a single meIn renal cell carcinoma the adrenal gland is the site of tastases in 1.3 to 2%.13s20 In our series adrenal involvement metastasis only in the fifth place, after the lungs, bones, was found in 11 patients (3.8%) who had advanced stage regional lymph nodes and main renal vein.23 In our series renal cell carcinoma with lymph node metastases (table 1). 35.7% of the patients with normal ipsilateral adrenal glands Similar results were found in other series: 5 of 8 patients had high stage disease (greater than stage pT3) and 18.9% reported on by Winter et all3 and all with adrenal involve- had lymph node metastases. Therefore, we conclude that ment reported on by Haab et all7 had lymph node metasta- both adrenal glands are not easily invaded by the tumor, ses. allowing the possibility of leaving the macroscopically norIn our series the likelihood ratio for adrenal involvement in mal adrenal gland in place for localized tumors not appearing relation t o metastatic regional lymph node disease was 5.2 to invade the upper pole boundaries of the kidney.
ADRENALECTOMY DURING RADICAL NEPHRECTOMY Adrenal lesions of more than 1 cm. can be easily detected by CT but this test does not always distinguish a metastatic lesion from an adenoma. Preoperatively, Haab e t a1 obtained a 60% positive predictive value for detecting adrenal metastases with CT.17 I n only 2 of our patients were the adrenal lesions suspected preoperatively. On the other hand, they can almost always be palpated intraoperatively.17 When only upper pole renal cell carcinoma is concerned, it is difficult to assess the adrenal involvement by CT, especially with large tumors. Assessment might also be difficult intraoperatively. In t h e upper pole with small tumors up to 2.5 cm. i n diameter not invading t h e renal capsule adjacent to the adrenal (stage Tl), the adrenals should be spared. In a n autopsy study on patients with renal cell carcinoma conducted by Saitoh e t al, ipsilateral and contralateral adrenal metastases were reported i n 19.1%and 11.5%,respectively.24 The percentage of contralateral adrenal involvement with micrometastases during radical nephrectomy remains unknown. Lemmers e t a1 reported a case of renal cell carcinoma with contralateral adrenal metastases occurring 15 years after radical nephrectomy, when the ipsilateral adrenal was not removed at operation and adrenalectomy was then possible without steroid replacement therapy postoperatively.25 Contralateral adrenal metastases are rare clinical conditions as a r e ipsilateral adrenal metastases, not by contiguity, appearing as a single metastasis or micrometastasis with a presumed potential for cure. Isolated adrenal metastases are estimated to occur i n 1.3 to 2% of the ipsilateral and 1.4%of t h e contralateral adrenal glands.ls,zo However, we still do not advise contralateral adrenal removal during radical nephrectomy. In conclusion, if we consider that adrenal metastases are present i n 4% of t h e patients during radical nephrectomy (table l),the adrenal glands are extirpated in 96% of the cases without any benefit to the patient. CONCLUSIONS
On review of our data and the literature, we conclude that adrenalectomy during radical nephrectomy should be performed only when a direct extension of the tumor from the kidney into the gland is suspected intraoperatively, or when 1 of the adrenal glands is the site of a single metastasis. Adrenal metastases, not by contiguity from the upper pole of the kidney, should be regarded as systemic disease and adrenal extirpation as palliative treatment. This stage of the disease should be classified as p W + in the TNM classification. Macroscopically normal adrenal glands should not be extirpated during radical nephrectomy. Since renal cell carcinoma is a n unusual disease, with metastases appearing many years after nephrectomy and sometimes at bizarre locations, we postulate that prophylactic surgery is unsuitable i n this situation.
1. 2.
3. 4.
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5. Skinner, D. G., Calvin, R. B., Vermillion, C. D., Pfister, R. C. and Leadbetter, W. F.: Diagnosis and management of renal cell carcinoma: a clinical and pathological study of 309 cases. Cancer, 28 1165, 1971. 6. Rafla, S.: Renal cell carcinoma: natural history and results of treatment. Cancer, 25 26, 1970. 7. Takatera, H., Maeda, O., Oka, T., Namiki, M., Nakamo, E.,
Matsuda, M., Arita, N., Jamshidi, J., Ushio, Y. and Sonoda,T.: Solitary late recurrence of renal cell carcinoma. J. Urol., 136 799, 1986. 8. Ljungberg, B., Duchek, M., Hietala, S. O., Roos, G. and Stenling,
R.: Renal cell carcinoma in a solitary kidney: late nephrectomy after 35 years and analysis of tumor deoxyribonucleic acid content. J. Urol., 139 350, 1978. 9. Robson, C. J.: Results of radical thoraco-abdominal nephrectomy in the treatment of renal cell carcinoma. In: Renal Tumors: Proceedings of the First International Symposium on Kidney Tumors. Edited by R. Kiiss, G. P. Murphy, S. Khoury and J. P. Karr. New York Alan R. Liss, Inc., p. 474, 1982. 10. Angervall, L. and Wahlqvist, L.: Follow-up and prognosis of renal carcinoma in a series operated by perifascial nephrectomy combined with adrenalectomy and retroperitoneal lymphadenectomy. Eur. Urol., 4 13, 1978. 11. Hohenfellner, R. and Zingg, E. J.: Urologie in Klinic und Praxis. New York: Georg Thieme Verlag, vol. 1, p. 504, 1982. 12. Robey, E. L. and Schellhammer, P. F.: The adrenal gland and renal cell carcinoma: is ipsilateral adrenalectomy a necessary component of radical nephrectomy. J. Urol., 135 453, 1986. 13. Winter, P., Miersch, W.-D., Vogel, J. and Jaeger, N.: On the necessity of adrenal extirpation combined with radical nephrectomy. J. Urol., 144:842, 1990. 14. Jaschke, W., van Kaick, G., Peter, S. and Palmtag, H.: Accuracy of computed tomography in staging of kidney tumors. Acta Rad., 2 3 593, 1982. 15. OBrien, W. M. and Lynch, J. H.: Adrenal metastases by renal cell carcinoma. Incidence a t nephrectomy. Urology, 2 9 605, 1987. 16. Jaeger, N. and Vahlensieck, W.: Prognose beim Neirenkarzinom. Lebensversicherungsmedizin,37:75, 1985. 17. Haab, F., Gattegno, B., Duclos, J . M., Tchala, It, Lagrange, L., Ouakil, E., Lukacs, B. and Thibault, P.: La surrenaleetomie el-
argie doit-elle etre systematique lorn de la nephredomie elargie pour cancer due rein? Revue de 119 dossiers. Prog. Urol., 1:889, 1991. 18. Saussine, C., Delepaul, B., Jacqumin, D. and Bollack, C.: Local-
isation surrenalienne dans les nephrectomies pour cancer due rein. Communication au 86eme Congres de l'AFU. Prog. Urol., 9 4, 1992. 19. Coulange, C.: Enquete epidemiologique des tumeurs du rein. Progres en Urologie, CCAFU, 2: 200, 1993. 20. Saitoh, H., Hida, M., Nakamura, K., Shimbo, T., Shiramizu, T. and Satoh, T.: Metastatic processes and a potential indication of treatment for metastatic lesions of renal adenocarcinoma. J. Urol., 128 916, 1982. 21. ODea, M. J., Zincke. H., Utz, D. C. and Bernatz. P. E.: The treatment bf renal cell carcinoma with solitary metastasis. J. Urol., 120 540, 1978. 22. Tolia, B. M. and Whitmore, W. E.: Solitary metastases from renal cell carcinoma. J. Urol., 114:836, 1975. REFERENCES 23. Williams, R. D.: Renal, perirenal and ureteral neoplasms. In: Adult and Pediatric Urology. Edited by J. Y. Gillenwater, J. T. Robson. C. J.: Radical neuhrectomv for renal cell carcinoma. J. Grayhack, S. S. Howards and J . W. Duckett. St. Louis: Mosby Urol.: 8 9 37, 1963. Year Book, Inc., vol. 1, chapt. 16, p. 582, 1991. Campbell. J . M. and Machin. D.: Medical Statistics, A Common Sense Approach. New York: John Wiley & Sons, p. 32, 1990. 24. Saitoh, H., Nakayama, M., Nakamura, K and Satoh, T.: Distant metastases of renal adenocarcinoma in nephrectomized cases. Bazeed, M. A,, Scharfe, T., Becht, E., Jurincic, C., Alken, P. and J . Urol., 127: 1092, 1982. Thiiroff, J . W.: Conservative surgery of renal cell carcinoma. 25. Lemmers, M., Ward, K., Hatch, T. and Stenzel, P.: Renal adenoEur. Urol., 12:238, 1986. carcinoma with solitary metastasis to the contralateral adreMorgan, W. R. and Zincke, H.: Progression and survival after nal gland report of 2 cases and review of the literature. J. renal conserving sureen for renal cell carcinoma: experience Urol., 141: 1177, 1989. in 104 patients &d eitended followup.J . Urol., 144:852,1990.
Vol. 153, 1415-1417,May 1995 Prinfed in U S A .
IS IPSILATERAL ADRENALECTOMY A NECESSARY COMPONENT OF RADICAL NEPHRECTOMY? M. SHALEV, B. CIPOLLA, F. GUILLE, F. STAERMAN
AND
B. LOBEL*
From the Department of Urology, Hopital Pontchaillou, Rennes, France
ABSTRACT
Due to t h e increased use of modern imaging systems during the last few years, kidney tumors are often diagnosed at an earlier and less advanced stage. This fact implies a reevaluation of t h e operative technique of radical nephrectomy that was recommended 30 years ago. The ipsilateral adrenal involvement during radical nephrectomy for renal cell carcinoma is assessed and the necessity of its extirpation is discussed. Between September 1987 and September 1993, we performed 299 radical nephrectomies for renal cell carcinoma and removed 285 ipsilateral adrenal glands. Eleven adrenal glands (3.8%) were involved with the kidney tumor and 274 (96.2%) were free of disease. I n 7 of the adrenal gland involved cases (63.6%) the tumor invaded the gland by direct extension from the superior pole of the kidney. In the other 4 cases the ipsilateral adrenal gland was affected by a metastatic lesion. In all 11adrenal gland involved cases the tumors were at a n advanced stage (the lowest was stage pT3N1). Our results led us to recommend adrenalectomy during radical nephrectomy only when direct extension of the kidney tumor into the gland is suspected (upper pole or large tumors) or when the adrenal is the site of a single metastasis. Macroscopically normal adrenal glands at radical nephrectomy should not be routinely extirpated. Metastatic renal cell carcinoma (not by contiguity) in the ipsilateral adrenal gland should be regarded as a stage M+ (distant metastasis) tumor. KEYWORDS:adrenal glands; adrenalectomy; kidney neoplasms; nephrectomy;carcinoma, renal cell
In 1963 Robson recommended radical nephrectomy including ipsilateral adrenalectomy as the treatment of choice for renal cell Carcinoma.’ This operation was universally accepted because of its relative simplicity and adherence to the surgical oncology principle of a “wide margin beyond the malignancy.” At that time adrenal involvement in renal cell carcinoma was estimated to be present in 5 to 10% of the cases. Due to the increased use of ultrasound and computerized tomography (CT) during the last decade, the incidence of small, low stage tumors has grown considerably. This high incidence of accidentally discovered low stage renal cell carcinoma gave rise to new ideas about a more conservative surgical approach. It was suggested that ipsilateral adrenalectomy should be performed only if the tumor was in the upper pole of the kidney, or when there was preoperative or intraoperative evidence of adrenal metastasis. However, some urologists still recommend adrenalectomy in patients undergoing radical nephrectomy. We assess the ipsilateral adrenal involvement in renal cell carcinoma to determine whether routine ipsilateral adrenalectomy during radical nephrectomy is still required.
ian vessels were dissected and tied. Disease was staged according to the 1992 TNM classification. To examine the possibility of predicting adrenal involvement in renal cell carcinoma in relation to stage or lymph node involvement, the likelihood ratio test was performed (Bayes’ theorem1.2 To test the likelihood ratio for adrenal involvement in relation to advanced T stage, patients were divided into 2 groups: group 1-stages T1 and T2 disease, and group 2-stages T3 and T4 cancer. Regarding lymph node involvement, the patients were divided into those with positive and negative lymph nodes. The test was not considered predictive of adrenal involvement for likelihood ratio values of less than 5 , while values of 5 to 10 were considered good prediction (but insufficient as a solitary test) and those greater than 10 as excellent prediction. Likelihood ratio is calculated by the formula true positivdnumber of adrenal invo1vement:false-positivdnumberof nonadrenal involvement. RESULTS
Involvement of the ipsilateral adrenal gland in renal cell carcinoma was found in 11 of 285 patients (3.8%),including PATIENTS AND METHODS 3 women and 8 men (mean age 59.4 years, table 1). All Between September 1987 and September 1993, 299 pa- adrenal glands were reviewed by the pathologist and no tients with renal cell carcinoma were treated surgically. Rad- incidental tumors were found in this series. In 7 of the 11 ical nephrectomy with ipsilateral adrenalectomy was per- patients with adrenal involvement the tumor invaded the formed in 179 men and 106 women 35 to 85 years old (mean gland by direct extension from the upper pole. In the other 4 age 64.6 years). The operative technique consisted of removal patients the renal tumor was in the mid or lower portion of of the tumor en bloc together with the adipose capsule, prox- the kidney and extension to the adrenal gland was by distant imal third of the ureter and adrenal gland, according to the metastasis. The renal cell carcinoma measured 6 to 15 cm. in anatomical boundaries of Gerota’s fascia. In addition, re- largest diameter. The disease was stage pT3c in 3 patients gional lymph nodes were excised, and the spermatic or ovar- and stage pT4a in 2. In the latter 2 patients the tumor invaded the peritoneum in 1 and the liver in 1. Lymph node Accepted for publication September 23, 1994. * Requests for reprints: Department of Urolo Hopital Pontchail- metastases were found in all 11 patients (9 stage N2 and 2 stage Nl). Distant metastases were found in the lung of IOU, Rue Henri Le Guilloux, 35033 Rennes Ce%k, France. 1415
1416
ADRENALECTOMY DURING RADICAL NEPHRECTOMY TABLE1. Tumor stage, location, and mechanism of adrenal involvement in patients with adrenal metastases
Pt.-Sex -Age
Stage
Location of TumorlKidney
Diameter (cm.)
1-M-70 2-M-66 3 - F -85 4-M-72 5-M-53 6-M-54 7-M-42 8-M-39 9 - F -57 10-F -55 11 -M - 6 1
T3cN2Mo T3cN2Mo T3cN2Mo T3cNlMo T3cN2Mo T3cN2Mo T4ah'2Mo T3cN2M1 T4aN2M1 T3cNlMo T3cN2Mo
Lower pole& Lower poldrt. Upper pole and mid portiodrt. Upper poldrt. Upper pole and mid portiodrt. Lower poldrt. Upper poldt. Upper poldrt. Upper poldrt. Upper poldt. Lower pole and mid portiodrt.
7 6 12 14 15 12 15 15 9 11 13
patients 8 and 9. Adrenal metastases were identified by CT preoperatively in only patients 4 and 6. The excised ipsilateral adrenal glands were free of disease in 274 patients (96.2%). Of these patients 98 (35.7%) had stage pT3 and 4 (1.4%) had stage pT4 carcinoma, with lymph node involvement in 52 (18.9%). The likelihood ratio for adrenal involvement was 2.7 in relation to T stage and 5.2 in relation to lymph node involvement (N stage). Therefore, we assume that in the case of nodal metastases the likelihood of adrenal involvement is high. Nodal involvement seems to be far more predictive of adrenal involvement than local spread of the tumor (likelihood ratio 5.2 compared to 2.7 when T stage is concerned). DISCUSSION
Mechanism of Adrenal Involvement Metastases Metastases Contiguous Contiguous Contiguous Metastases Contiguous Contiguous Contiguous Contiguous Metastases
TABLE2 . Frequency of adrenal metastases in renal cell carcinoma after nephrectomy Reference
No. Pts
No. Adrenal Metastases (W)
88 4 (4.5) Robsong 58 6 (10) Angervall and Wahlqvist'" 429 5 (1.2) Hohenfellner and Zingg" 82 2 (2.4) Rnbey and Schellhammer12 138 8 (5.8) Winter et all3 111 3 (2.8) Jaschke et all4 72 4 (5.5) O'Brien and Lynch15 161 9 (5.6) Jaeger and Vahlensieck'6 119 6 (5) Haab et all7 156 12 (8.3) Saussine et all8 233 CoulangeIg.* 9 (3.9) 285 11 (3.8) Present study Totals 1,932 79 (4.08) * Comitd de Cancerologie de I'association Franqaise d'Urologie.
In 1963, when Robson described the surgical approach to radical nephrectomy,' renal cell carcinoma was diagnosed mostly by the appearance of clinical symptoms. All urological but when related t o the local stage of the tumor (T stage) it textbooks from that period described the classical triad of was only 2.7. In other words, adrenal involvement seems to flank pain, flank mass and hematuria as pathognomonic for depend more on the lymphatic spread than on the local T renal cell carcinoma. As a result of late diagnosis, most of the stage of the tumor but it should also be emphasized that to patients had large volume tumors and advanced stage dis- our knowledge adrenal involvement with renal cell carciease. Due to the increased use of ultrasound and CT during noma of less than 5 cm. has never been reported.17 Adrenalectomy during radical nephrectomy is also justified the last decade, there has been an increase in the incidence of small renal cell carcinoma detected at an early stage. This when it is the site of a solitary metastasis. A better prognosis tendency of early diagnosis led surgeons to consider kidney was reported (30% survival at 5 years) when solitary metassparing surgery when the tumors were small (mean 3.3 cm.) tases were removed,21*22an approach valid for the contralatera1 adrenal as well. and of low grade and ~ t a g e . 3 . ~ Is adrenalectomy justified when the adrenal is macroscopThe staging classification was also adjusted to this new approach, differentiating between stage T1 renal cell carci- ically normal? Winter et al, analyzing 138 radical nephrecnoma (a localized tumor up to 2.5 cm. in diameter that does tomies, found 8 patients (5.8%) with adrenal involvement, 3 not distort the calices and renal pelvis, in which case renal of whom (2.1%) had adrenal micrometastases that could not sparing surgery should be considered) and stage T2 disease be diagnosed preoperatively or intraoperatively.13 Based on (for which radical nephrectomy is still mandatory). Never- these findings, they concluded that ipsilateral adrenalectomy theless, the benefit of radical nephrectomy compared to sim- should be performed routinely to eliminate the potential miple nephrectomy considering the progression of the disease crometastases-bearing adrenal glands with the possibility of and survival rates has not yet been proved.5.6 Moreover, being cured. We do not agree with the concept that adrenal renal cell carcinoma is an unpredictable tumor. Metastases micrometastases are a local extension from the renal cell have been reported to appear as late as 13years after radical carcinoma. In fact, adrenal micrometastases, invading the nephrectomy and sometimes were dormant for as long as 35 gland lymphogenously or hematogenously, are rather the years when left untreated.7.8 expression of a systemic disease that should be a t a higher Despite the tendency to perform more conservative surgery stage in the TNM classification, that is stage pTxM+ instead during the last few years, urologists still perform ipsilateral of pT3a. Routine ipsilateral adrenalectomy for the presumed adrenalectomy during nephrectomy for renal cancer as a benefit of2.1% of the patients who at least theoretically have matter of routine. Adrenal involvement in radical nephrec- a systemic disease with multiple micrometastases is not justomy specimens has been reported to occur in 1.2 to 10% of tified in our opinion. the patients (mean 4.08%, table 2),9-19 and as a single meIn renal cell carcinoma the adrenal gland is the site of tastases in 1.3 to 2%.13s20 In our series adrenal involvement metastasis only in the fifth place, after the lungs, bones, was found in 11 patients (3.8%) who had advanced stage regional lymph nodes and main renal vein.23 In our series renal cell carcinoma with lymph node metastases (table 1). 35.7% of the patients with normal ipsilateral adrenal glands Similar results were found in other series: 5 of 8 patients had high stage disease (greater than stage pT3) and 18.9% reported on by Winter et all3 and all with adrenal involve- had lymph node metastases. Therefore, we conclude that ment reported on by Haab et all7 had lymph node metasta- both adrenal glands are not easily invaded by the tumor, ses. allowing the possibility of leaving the macroscopically norIn our series the likelihood ratio for adrenal involvement in mal adrenal gland in place for localized tumors not appearing relation t o metastatic regional lymph node disease was 5.2 to invade the upper pole boundaries of the kidney.
ADRENALECTOMY DURING RADICAL NEPHRECTOMY Adrenal lesions of more than 1 cm. can be easily detected by CT but this test does not always distinguish a metastatic lesion from an adenoma. Preoperatively, Haab e t a1 obtained a 60% positive predictive value for detecting adrenal metastases with CT.17 I n only 2 of our patients were the adrenal lesions suspected preoperatively. On the other hand, they can almost always be palpated intraoperatively.17 When only upper pole renal cell carcinoma is concerned, it is difficult to assess the adrenal involvement by CT, especially with large tumors. Assessment might also be difficult intraoperatively. In t h e upper pole with small tumors up to 2.5 cm. i n diameter not invading t h e renal capsule adjacent to the adrenal (stage Tl), the adrenals should be spared. In a n autopsy study on patients with renal cell carcinoma conducted by Saitoh e t al, ipsilateral and contralateral adrenal metastases were reported i n 19.1%and 11.5%,respectively.24 The percentage of contralateral adrenal involvement with micrometastases during radical nephrectomy remains unknown. Lemmers e t a1 reported a case of renal cell carcinoma with contralateral adrenal metastases occurring 15 years after radical nephrectomy, when the ipsilateral adrenal was not removed at operation and adrenalectomy was then possible without steroid replacement therapy postoperatively.25 Contralateral adrenal metastases are rare clinical conditions as a r e ipsilateral adrenal metastases, not by contiguity, appearing as a single metastasis or micrometastasis with a presumed potential for cure. Isolated adrenal metastases are estimated to occur i n 1.3 to 2% of the ipsilateral and 1.4%of t h e contralateral adrenal glands.ls,zo However, we still do not advise contralateral adrenal removal during radical nephrectomy. In conclusion, if we consider that adrenal metastases are present i n 4% of t h e patients during radical nephrectomy (table l),the adrenal glands are extirpated in 96% of the cases without any benefit to the patient. CONCLUSIONS
On review of our data and the literature, we conclude that adrenalectomy during radical nephrectomy should be performed only when a direct extension of the tumor from the kidney into the gland is suspected intraoperatively, or when 1 of the adrenal glands is the site of a single metastasis. Adrenal metastases, not by contiguity from the upper pole of the kidney, should be regarded as systemic disease and adrenal extirpation as palliative treatment. This stage of the disease should be classified as p W + in the TNM classification. Macroscopically normal adrenal glands should not be extirpated during radical nephrectomy. Since renal cell carcinoma is a n unusual disease, with metastases appearing many years after nephrectomy and sometimes at bizarre locations, we postulate that prophylactic surgery is unsuitable i n this situation.
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