SURGERY FOR PULMONARY METASTASES FROM
RENAL CELL CARCINOMA Army Experience from 1977-1987 CPT. JAMES B. THRASHER, MC (USA) COL. JEFFREY R. CLARK, MC (USA) MAJ. BRUCE P. CLELAND, MC (USA) From the General Surgery Service, Fitzsimons Army Medical Center, Aurora, Colorado
-ABSTRACT--The Army Medical Centers" combined ten-year experience (1977-1987) with renal cell carcinoma metastatic to the lung is presented. Those patients who underwent resection oJ the lung metastases were compared with those who did not. Certain Jactors within the two groups were analyzed mainly for effect on survival: number and location of pulmonary metastases, disease-free interval from nephrectomy, extent of lung resection, and synchronous vs asynchronous metastases. Comparisons were made with reports from the literature, and conclusions were made in reference to indications for resection and other modes of therapy.
In spite of the recent advances in the management of solid tumors with eytotoxie agents as well as hormonal agents, advanced renal cell carcinoma has remained recalcitrant to all medical modes of therapy. It is evident from the irecent literature that aggressive surgical ~management remains the standard of care for this disease. Churchill and Barney are generally credited as catalysts for the beginning of aggres:~isivesurgical management of pulmonary metasrases from renal cell carcinoma. In 1938 they 1 !~reported the first case in which a patient underwent both nephrectomy and excision of a soli;tary pulmonary metastasis. The patient underwent a partial lobectomy in 1933 and died itwenty-three years later of coronary artery dis:ease.2 Since that time, many studies have re!,,ported excellent survival rates in patients with nephrectomy and excision of solitary pulmo-
i
The opinions or assertions expressed in this article are those of :the authors a n d are not to be construed as official or as necessarily r e f l e c t i n g the views of the D e p a r t m e n t of the A r m y or the Department of Defense.
UROLOGY
/
JUNE 1990
/
V O L U M E XXXV. N U M B E R 6
nary metastases, and more recently the subject of surgery for both multiple unilateral and multiple bilateral pulmonary metastases has come into question. We, therefore, undertook a multieenter review of the Army's combined tenyear experience with surgery for pulmonary metastases from renal cell carcinoma to specifically address the question of increased survival with aggressive surgical management not only in patients with solitary pulmonary metastases but also those with multiple unilateral and multiple bilateral pulmonary metastases. Material and Methods All patients with renal cell carcinoma metastatic to the lung treated at the Army's eight medical centers between the period 1977 and 1987 were included in the study. A total of 142 charts were reviewed with 126 noted to be adequate for comparison. The other 16 patients were either lost to follow-up or received treatment at another facility. Of the t26 patients, a total of 15 patients underwent resection of their 487
TABLEI. Pulmonary resection group: number and location of mets Number of Metastases-1 2 3 4 1 1 Number of patients 8 1 Number bilateral . . Survival years 1 1
70 60
50
40 3C 2C
•
•
,
•
4 5
1C
C
2 3
20-30
80-40
40-50
50-60
60-70
70-80
80-90
AGE IN Y E A R S
FIGURE 1.
Distribution of patients by age and sex.
pulmonary metastases. However, 1 patient was excluded from the study because he committed suicide after lobectomy and two others did not undergo resection for cure. A total of 114 patients did :not undergo pulmonary resection. A total of 115 men (81%) with a mean age of fifty seven and 27 women (19 % ) with a mean age of fifty nine were included i n this study• The majority of the patients were in their sixth and seventh decades of life (Fig. 1). Two groups were identified: (1) Pulmonary resection group or those who underwent curative resection of their lung metastases, and (2) pulmonary nonresection group or those who did not undergo lung resection. The general criteria for operability in the pulmonary resection group were that the primary disease be under control, no evidence of extrapulmonary disease by extensive workup, and no other contraindieations to surgery. A complete workup, including physical examination, chest x-ray film, whole lung tomography, bone scan, liver rune, tion tests, brain scan, and liver-spleen scan was done to rule out extrapulmonary disease. Statistical methods In analyzing our differences in survival, we used two tests: (1) A one-tailed independent Student t-test, and (2) the Mann-Whitney U test. In making correlations between the data, we used Pearson's correlation analysis.
.
.
1
1
3
6
•
7
•
8 9
1 . •
3 1
•
•
those 114 patients, 68 underwent nephrectomy. In this subgroup, metastases developed after nephrectomy (asynchronous metastases) in 32 patients, and in 36 patients, the metastatic lesions were diagnosed concurrently with the primary tumor (synchronous metastases)• A signifi c a n t d i f f e r e n c e in m e a n s u r v i v a l from nephrectomy was noted with 34.9 months for: the asynchronous subgroup and 11.2 months for the synchronous subgroup (p = 0•00001). A total of 79 patients presented initially with multiple metastases to the lung, with 37 of these patients undergoing nephrectomy for reasons such as continued pain or continued hemorrhage. Forty-two of the patients did not undergo nephreetomy secondary to their recta: static lung disease• A signifieant difference in m e a n survival was again noted with 11.1 months (calculated from time of nephrectomy) in the nephreetomy group and in the non" nephrectomy group, 6.6 months (calculated from the time of diagnosis). In 36 of the 42 patients (86%) who did not undergo nephrectomy, renal cell carcinoma was diagnosed histologically, either from autopsy or biopsy of the lesion.
Pulmonary nonresection group A total of 114 patients did not undergo pulmonary resection for their lung metastases. Of
Pulmonary resection group Number and location of lung metastases. Twelve patients underwent resection of their: lung metastases and the survival in relation to the number and location of the lung metastases is seen in Table I. Two patients had 4 metas, rases, 1 had 3, 1 had 2, and 8 patients had soli= tary metastases at the time of their consider~ ation for lung resection. Two patients were
488
UtlOLOCY
Results
J U N E1 9 9 0
VOLUMEXXXV, NUMBEtl 6
noted to have bilateral metastases, and 10 patients had unilateral metastases. The 2 patients who had bilateral metastases both underwent staged thoraeotomies. There was no correlation between the number of metastases and survival nor was there a correlation between the location of the metastases and survival.
Disease-free interval and survival In the pulmonary resection group, the disease-free interval from resection of the primary tumor to the appearance of lung metastasis was analyzed. The mean disease-flee interval in the group, as a whole, was 38.8 months. A positive correlation was found between the disease-free interval and survival from nephrectomy. As the disease-free interval increased, so did the total survival[ time. However, in contrast to previous studies, no specific disease-flee interval could b e identified where survival changed significantly. Number and type of operation Five of the patients were submitted to two operations with a mean survival of 41.6 months after nephreetomy and 19.8 months after first resection. Seven of the patients underwent a single operation, with a mean survival of 70.7 months after nephreetomy and 36.4 months after the first reseetion. However, the difference was not significant according to the MannWhitney U test (p = 0.08). A lobeetomy alone was performed on only 1 patient, and 2 patients u n d e r w e n t both a wedge resection and a lobeetomy with a slightly better survival in the lobeetomy group, as a whole. The r e m a i n i n g patients u n d e r w e n t wedge resection alone. The survival difference was not signifieant. Synchronous vs asynchronous pulmonary metastases The survival of the synehronous (3 patients) and asynchronous (9 patients) subgroups were compared. There was a marked differenee in mean survival from nephreetomy with 19.0 m o n t h s for the synchronous subgroup and 71.8 months for the asynchronous subgroup (p = 0.01, Student t-test). Mean survival from resection of the lung metastases was nineteen months for the synchronous subgroup and thirty-three months for the asynchronous subgroup (p = 0.16, Student t-test). This difference was not signifieant.
UROLOGY
/
JUNE 1990
/
VOLUME XXXV, NUMBER 6
Pulmonary resection vs nonresection Finally, survival was compared between the pulmonary reseetion group (12 patients) and the subgroup of pulmonary nonreseetion patients (132 patients) in w h o m pulmonary metastases developed after nephreetomy. The survival from the time of initial resection of the pulmonary metastases until death in the resection group was eompared with the survival from the time of diagnosis of the pulmonary metastases until death in the nonresection group. Four patients from each group are still alive, and their survivals were calculated up to February, 1988. A significantly better survival was noted in the pulmonary resection group, with a mean survival of 29.5 months compared with 14.8 months for the nonreseetion group (p =
0.003).
Control cases From the hospital records of a total of 142 patients with renal cell carcinoma metastatic to the lung, 2 patients were found who could have had pulmonary resection for cure but did not have resection. In both cases, the lesions were biopsy-proved renal cell carcinoma, 1 patient had 3 nodules in the left lung and the other had a solitary left upper lobe nodule. Both had previously had a nephreetomy and presented after a disease-free interval with lung metastases and no other extrapulmonary disease. One patient had a survival of sixteen months and the other thirteen months with a mean survival of 14.5 months. The reason not to operate in both cases was the fact that the patients were to undergo an observation period to see if nephrectomy would cause regression of the lung metastases. [n both cases, death occurred secondary to metastatic renal cell carcinoma to the tung. Medical therapy One hundred eleven patients of the 142 in the study were given a total of 51 different agents in various combinations. Only two partial responses were achieved using vinblastine sulfate (Velban) in 1 patient (no growth of pulmonary lesion x 8 months) and tamoxifen in the other patient (no growth of pulmonary lesion x 7 months). One complete response with interleukimII therapy (complete regression for 5 months) was achieved (Table II). Comment In spite of recent advances in chemotherapeutic, hormonal, and i m m u n o t h e r a p e u t i c
489
"D,~BLSl I
~,i~rdic'd tr~erapy A r m y experience ,[97 ;u1987
Therapy Chemo. Hormonal Imrnuno.
No. of Pts 54 48 9
No. 9f Age ::ts ,1( '~ ~-
Response C P 0 1 0 1 1 0
therapy for solid tumors, ren~d cell carcinoma has remained recalcitrant to these modes of therapy. The move towa:rd a~;[gressive surgical management of renal cell earc:.inoma was initiated with Barney and Cihurehill's ~ reported success with removal of a solitary lung metastasis from renal cell carcinoma in 1938. Since that time, more aggressive surgical attempts at lung metastases have been initiated due to otherwise futile attempts with other modes of therapy. The beneficial effects of aggressive surgical treatment of solitary metastases on patient survival was shown by Middleton 3 with 59 patients and a 34-percent, five-year survival, Tolia and Whitrnore 4 with 19 patients and a 35-percent, five-year survival, and finally confirmed by O'Dea e t al. 5 in their series with 44 patients in which the longest survival was 7.5 years. Althoug:h it has been shown without question that resection of solitary metastatic pulmonary lesions improves survival, many questions with reference to bilateral and multiple renal cell metastases to the lung remain controversial. In addressing these questions, we found no significant difference in survival between the group of patients with greater than one pulmonary metastases and the group with solitary pulmonary metastases.. This correlates well with the Dernevik e t al. 6 findings where 33 patients underwent resection for pulmonary metastases from renal cell carcinoma; 15 had solitary metastases, and 18 had more than 1 metastasis with no significant difference in survival between the two groups. We also found no significant difference in survival between thOse patients with unilateral metastases and those with bilateral metastases, confirming the findings of Takita et al. ~ However, he looked at lung metastases from other primary sites as well as those from renal cell carcinoma. In our search for a control group, we found that the 2 patients used as controls could have undergone pulmonary resection and were, in fact, good surgical candidates. However, it was
490
decided not to reseet their lung lesions. Their mean survival of 14.5 months correlated more closely with that of our pulmonary nonresection group (mean survival 14.8 months) than our pulmonary resection group (mean survival 29.5 months). Our findings of better survival in the asynchronous subgroup vs synchronous subgroup correlates well with the findings of O'Dea e t al., 5 Dernevik e t al., 6 and Golimbu e t al. s Although we did not find a specific disease-free survival where the prognosis changed signifieantly, we could say that as the disease-free interval after nephreetomy increases so does the total survival time. Although our findings correlated well with those reported in the recent literature, one result of our study contradicted previous studies. We found a significantly better survival in those patients with multiple lung metastases who underwent nephrectomy than those who did not undergo nephrectomy. The recent literature advocates nephreetomy in patients who present with multiple metastases only in cases of continued hemorrhage from the primary tumor or intractable pain2 In our study, the patients who had multiple pulmonary metastases and underwent nephrectomy were similar in severity of the disease to those who did not undergo nephreetomy. In spite of this, the group of patients who underwent nephreetomy had a better survival as a whole (11.1 months vs 6.6 months). As a final consideration, the approach to these lesions must be contemplated. Takita e t al.7 advocated a staged thoracotomy for bilat-: eral tumors unless they were noted to have a very short doubling time. In that situation, he advocated median sternotomy and resection of the pulmonary metastases bilaterally. In our resection group, both patients with bilateral metastases underwent staged thoraeotomies with ~ good results. Conclusions Our findings correlate well with those in the literature where it was found that ehemother~' apy and hormonal therapy continue to have no proved efficacy against metastatic renal cell, carcinoma. We are just beginning to see a little~ , . :. • • ; pr:gr=:n~llehd~nn~ncUonnttihneyeaspyAggressive sur gf g 1 u s to be the standard care for renal cell carcinoma with pulm o/: nary metastases. We found that (1) even wit~
UROLOGY
JUNE 1990
i
VOLUME XXXV, NUMBER 6
multiple distant metastases, nephrectomy prolonged survival, (2) a better prognosis with ~synehronous metastases than synchronous, (3) the greater the disease-free interval, the longer ~he survival, (4) no significant difference in suri!yival between resection of solitary metastases !land resection of 2-4 metastases or unilateral vs ~bilateral metastases, and (5) resection of pulmoaary metastases, when indicated, prolonged urvival. Certain criteria for operability must be met n spite of the fact that surgery is the only effecive modality that we have to offer these patients' These are (1) primary disease must be hnder control or controllable, (2) extra)ulmonary disease must be under control or ;ontrollable by surgery, and (3) bilateral multi,le pulmonary metastases must be approaehed ~by staged thoraeotomy or, especially in tumors iwith short doubling times, with median sterinotomy.
i
JUNE 1990 / VOLUME XXXV, NUMBER 6 U R /O L O G Y
Aurora, Colorado 80045-5001 (DR. THRASHER) References 1. Barney JD, and Churchill Ej: AdenocarcinQma of the kidney with metastasis to the lung: cured by nephrectomy and lobectomy, J Uro142:269 (1939). 2. Wflkins EW, Burke JE and Head JM: The surgical management of metastatic neoplasms in the lung, J Thorac Cardiovasc Surg 42:298 (1961). 3. Middleton RG: Surgery for metastatic renal cell carcinoma. J UroI 97:973 (1967). 4. Tolia BM, and Whitmore WF Jr: Solitary metastasis from renal cell carcinoma, J urol 114:836 (1975). 5. O'Dea MJ, Zineke H, Utz DC, and Bernatz PE: The treatment of renal cell carcinoma with solitary metastasis, J Urol 120: 540 (1978). 6. Dernevik L, Berggren H, Larsson S, and Roberts D: Surgieal removal of pulmonary metastases from renal cell carcinoma, Scand J Urol Nephrol 19:133 (1985). 7. Takita H, et al: The surgical management of multiple lung metastases, Ann Thorae Surg 24:359 (1977). 8, Golimbu M, A1-Askari S, Tessler A, and Morales P: Aggressive treatment of metastatic renal cancer, J Urol 136:805 (1986), 9. deKernian JB: Renal tumors, in Walsh PC~ Gittes RF, Perlmutter AD, and Stamey TA (Eds): Campbell's Urology, ed 5, Philadelphia, WB Saunders, 1986, pp 1329-1332
491
RENAL CELL CARCINOMA Army Experience from 1977-1987 CPT. JAMES B. THRASHER, MC (USA) COL. JEFFREY R. CLARK, MC (USA) MAJ. BRUCE P. CLELAND, MC (USA) From the General Surgery Service, Fitzsimons Army Medical Center, Aurora, Colorado
-ABSTRACT--The Army Medical Centers" combined ten-year experience (1977-1987) with renal cell carcinoma metastatic to the lung is presented. Those patients who underwent resection oJ the lung metastases were compared with those who did not. Certain Jactors within the two groups were analyzed mainly for effect on survival: number and location of pulmonary metastases, disease-free interval from nephrectomy, extent of lung resection, and synchronous vs asynchronous metastases. Comparisons were made with reports from the literature, and conclusions were made in reference to indications for resection and other modes of therapy.
In spite of the recent advances in the management of solid tumors with eytotoxie agents as well as hormonal agents, advanced renal cell carcinoma has remained recalcitrant to all medical modes of therapy. It is evident from the irecent literature that aggressive surgical ~management remains the standard of care for this disease. Churchill and Barney are generally credited as catalysts for the beginning of aggres:~isivesurgical management of pulmonary metasrases from renal cell carcinoma. In 1938 they 1 !~reported the first case in which a patient underwent both nephrectomy and excision of a soli;tary pulmonary metastasis. The patient underwent a partial lobectomy in 1933 and died itwenty-three years later of coronary artery dis:ease.2 Since that time, many studies have re!,,ported excellent survival rates in patients with nephrectomy and excision of solitary pulmo-
i
The opinions or assertions expressed in this article are those of :the authors a n d are not to be construed as official or as necessarily r e f l e c t i n g the views of the D e p a r t m e n t of the A r m y or the Department of Defense.
UROLOGY
/
JUNE 1990
/
V O L U M E XXXV. N U M B E R 6
nary metastases, and more recently the subject of surgery for both multiple unilateral and multiple bilateral pulmonary metastases has come into question. We, therefore, undertook a multieenter review of the Army's combined tenyear experience with surgery for pulmonary metastases from renal cell carcinoma to specifically address the question of increased survival with aggressive surgical management not only in patients with solitary pulmonary metastases but also those with multiple unilateral and multiple bilateral pulmonary metastases. Material and Methods All patients with renal cell carcinoma metastatic to the lung treated at the Army's eight medical centers between the period 1977 and 1987 were included in the study. A total of 142 charts were reviewed with 126 noted to be adequate for comparison. The other 16 patients were either lost to follow-up or received treatment at another facility. Of the t26 patients, a total of 15 patients underwent resection of their 487
TABLEI. Pulmonary resection group: number and location of mets Number of Metastases-1 2 3 4 1 1 Number of patients 8 1 Number bilateral . . Survival years 1 1
70 60
50
40 3C 2C
•
•
,
•
4 5
1C
C
2 3
20-30
80-40
40-50
50-60
60-70
70-80
80-90
AGE IN Y E A R S
FIGURE 1.
Distribution of patients by age and sex.
pulmonary metastases. However, 1 patient was excluded from the study because he committed suicide after lobectomy and two others did not undergo resection for cure. A total of 114 patients did :not undergo pulmonary resection. A total of 115 men (81%) with a mean age of fifty seven and 27 women (19 % ) with a mean age of fifty nine were included i n this study• The majority of the patients were in their sixth and seventh decades of life (Fig. 1). Two groups were identified: (1) Pulmonary resection group or those who underwent curative resection of their lung metastases, and (2) pulmonary nonresection group or those who did not undergo lung resection. The general criteria for operability in the pulmonary resection group were that the primary disease be under control, no evidence of extrapulmonary disease by extensive workup, and no other contraindieations to surgery. A complete workup, including physical examination, chest x-ray film, whole lung tomography, bone scan, liver rune, tion tests, brain scan, and liver-spleen scan was done to rule out extrapulmonary disease. Statistical methods In analyzing our differences in survival, we used two tests: (1) A one-tailed independent Student t-test, and (2) the Mann-Whitney U test. In making correlations between the data, we used Pearson's correlation analysis.
.
.
1
1
3
6
•
7
•
8 9
1 . •
3 1
•
•
those 114 patients, 68 underwent nephrectomy. In this subgroup, metastases developed after nephrectomy (asynchronous metastases) in 32 patients, and in 36 patients, the metastatic lesions were diagnosed concurrently with the primary tumor (synchronous metastases)• A signifi c a n t d i f f e r e n c e in m e a n s u r v i v a l from nephrectomy was noted with 34.9 months for: the asynchronous subgroup and 11.2 months for the synchronous subgroup (p = 0•00001). A total of 79 patients presented initially with multiple metastases to the lung, with 37 of these patients undergoing nephrectomy for reasons such as continued pain or continued hemorrhage. Forty-two of the patients did not undergo nephreetomy secondary to their recta: static lung disease• A signifieant difference in m e a n survival was again noted with 11.1 months (calculated from time of nephrectomy) in the nephreetomy group and in the non" nephrectomy group, 6.6 months (calculated from the time of diagnosis). In 36 of the 42 patients (86%) who did not undergo nephrectomy, renal cell carcinoma was diagnosed histologically, either from autopsy or biopsy of the lesion.
Pulmonary nonresection group A total of 114 patients did not undergo pulmonary resection for their lung metastases. Of
Pulmonary resection group Number and location of lung metastases. Twelve patients underwent resection of their: lung metastases and the survival in relation to the number and location of the lung metastases is seen in Table I. Two patients had 4 metas, rases, 1 had 3, 1 had 2, and 8 patients had soli= tary metastases at the time of their consider~ ation for lung resection. Two patients were
488
UtlOLOCY
Results
J U N E1 9 9 0
VOLUMEXXXV, NUMBEtl 6
noted to have bilateral metastases, and 10 patients had unilateral metastases. The 2 patients who had bilateral metastases both underwent staged thoraeotomies. There was no correlation between the number of metastases and survival nor was there a correlation between the location of the metastases and survival.
Disease-free interval and survival In the pulmonary resection group, the disease-free interval from resection of the primary tumor to the appearance of lung metastasis was analyzed. The mean disease-flee interval in the group, as a whole, was 38.8 months. A positive correlation was found between the disease-free interval and survival from nephrectomy. As the disease-free interval increased, so did the total survival[ time. However, in contrast to previous studies, no specific disease-flee interval could b e identified where survival changed significantly. Number and type of operation Five of the patients were submitted to two operations with a mean survival of 41.6 months after nephreetomy and 19.8 months after first resection. Seven of the patients underwent a single operation, with a mean survival of 70.7 months after nephreetomy and 36.4 months after the first reseetion. However, the difference was not significant according to the MannWhitney U test (p = 0.08). A lobeetomy alone was performed on only 1 patient, and 2 patients u n d e r w e n t both a wedge resection and a lobeetomy with a slightly better survival in the lobeetomy group, as a whole. The r e m a i n i n g patients u n d e r w e n t wedge resection alone. The survival difference was not signifieant. Synchronous vs asynchronous pulmonary metastases The survival of the synehronous (3 patients) and asynchronous (9 patients) subgroups were compared. There was a marked differenee in mean survival from nephreetomy with 19.0 m o n t h s for the synchronous subgroup and 71.8 months for the asynchronous subgroup (p = 0.01, Student t-test). Mean survival from resection of the lung metastases was nineteen months for the synchronous subgroup and thirty-three months for the asynchronous subgroup (p = 0.16, Student t-test). This difference was not signifieant.
UROLOGY
/
JUNE 1990
/
VOLUME XXXV, NUMBER 6
Pulmonary resection vs nonresection Finally, survival was compared between the pulmonary reseetion group (12 patients) and the subgroup of pulmonary nonreseetion patients (132 patients) in w h o m pulmonary metastases developed after nephreetomy. The survival from the time of initial resection of the pulmonary metastases until death in the resection group was eompared with the survival from the time of diagnosis of the pulmonary metastases until death in the nonresection group. Four patients from each group are still alive, and their survivals were calculated up to February, 1988. A significantly better survival was noted in the pulmonary resection group, with a mean survival of 29.5 months compared with 14.8 months for the nonreseetion group (p =
0.003).
Control cases From the hospital records of a total of 142 patients with renal cell carcinoma metastatic to the lung, 2 patients were found who could have had pulmonary resection for cure but did not have resection. In both cases, the lesions were biopsy-proved renal cell carcinoma, 1 patient had 3 nodules in the left lung and the other had a solitary left upper lobe nodule. Both had previously had a nephreetomy and presented after a disease-free interval with lung metastases and no other extrapulmonary disease. One patient had a survival of sixteen months and the other thirteen months with a mean survival of 14.5 months. The reason not to operate in both cases was the fact that the patients were to undergo an observation period to see if nephrectomy would cause regression of the lung metastases. [n both cases, death occurred secondary to metastatic renal cell carcinoma to the tung. Medical therapy One hundred eleven patients of the 142 in the study were given a total of 51 different agents in various combinations. Only two partial responses were achieved using vinblastine sulfate (Velban) in 1 patient (no growth of pulmonary lesion x 8 months) and tamoxifen in the other patient (no growth of pulmonary lesion x 7 months). One complete response with interleukimII therapy (complete regression for 5 months) was achieved (Table II). Comment In spite of recent advances in chemotherapeutic, hormonal, and i m m u n o t h e r a p e u t i c
489
"D,~BLSl I
~,i~rdic'd tr~erapy A r m y experience ,[97 ;u1987
Therapy Chemo. Hormonal Imrnuno.
No. of Pts 54 48 9
No. 9f Age ::ts ,1( '~ ~-
Response C P 0 1 0 1 1 0
therapy for solid tumors, ren~d cell carcinoma has remained recalcitrant to these modes of therapy. The move towa:rd a~;[gressive surgical management of renal cell earc:.inoma was initiated with Barney and Cihurehill's ~ reported success with removal of a solitary lung metastasis from renal cell carcinoma in 1938. Since that time, more aggressive surgical attempts at lung metastases have been initiated due to otherwise futile attempts with other modes of therapy. The beneficial effects of aggressive surgical treatment of solitary metastases on patient survival was shown by Middleton 3 with 59 patients and a 34-percent, five-year survival, Tolia and Whitrnore 4 with 19 patients and a 35-percent, five-year survival, and finally confirmed by O'Dea e t al. 5 in their series with 44 patients in which the longest survival was 7.5 years. Althoug:h it has been shown without question that resection of solitary metastatic pulmonary lesions improves survival, many questions with reference to bilateral and multiple renal cell metastases to the lung remain controversial. In addressing these questions, we found no significant difference in survival between the group of patients with greater than one pulmonary metastases and the group with solitary pulmonary metastases.. This correlates well with the Dernevik e t al. 6 findings where 33 patients underwent resection for pulmonary metastases from renal cell carcinoma; 15 had solitary metastases, and 18 had more than 1 metastasis with no significant difference in survival between the two groups. We also found no significant difference in survival between thOse patients with unilateral metastases and those with bilateral metastases, confirming the findings of Takita et al. ~ However, he looked at lung metastases from other primary sites as well as those from renal cell carcinoma. In our search for a control group, we found that the 2 patients used as controls could have undergone pulmonary resection and were, in fact, good surgical candidates. However, it was
490
decided not to reseet their lung lesions. Their mean survival of 14.5 months correlated more closely with that of our pulmonary nonresection group (mean survival 14.8 months) than our pulmonary resection group (mean survival 29.5 months). Our findings of better survival in the asynchronous subgroup vs synchronous subgroup correlates well with the findings of O'Dea e t al., 5 Dernevik e t al., 6 and Golimbu e t al. s Although we did not find a specific disease-free survival where the prognosis changed signifieantly, we could say that as the disease-free interval after nephreetomy increases so does the total survival time. Although our findings correlated well with those reported in the recent literature, one result of our study contradicted previous studies. We found a significantly better survival in those patients with multiple lung metastases who underwent nephrectomy than those who did not undergo nephrectomy. The recent literature advocates nephreetomy in patients who present with multiple metastases only in cases of continued hemorrhage from the primary tumor or intractable pain2 In our study, the patients who had multiple pulmonary metastases and underwent nephrectomy were similar in severity of the disease to those who did not undergo nephreetomy. In spite of this, the group of patients who underwent nephreetomy had a better survival as a whole (11.1 months vs 6.6 months). As a final consideration, the approach to these lesions must be contemplated. Takita e t al.7 advocated a staged thoracotomy for bilat-: eral tumors unless they were noted to have a very short doubling time. In that situation, he advocated median sternotomy and resection of the pulmonary metastases bilaterally. In our resection group, both patients with bilateral metastases underwent staged thoraeotomies with ~ good results. Conclusions Our findings correlate well with those in the literature where it was found that ehemother~' apy and hormonal therapy continue to have no proved efficacy against metastatic renal cell, carcinoma. We are just beginning to see a little~ , . :. • • ; pr:gr=:n~llehd~nn~ncUonnttihneyeaspyAggressive sur gf g 1 u s to be the standard care for renal cell carcinoma with pulm o/: nary metastases. We found that (1) even wit~
UROLOGY
JUNE 1990
i
VOLUME XXXV, NUMBER 6
multiple distant metastases, nephrectomy prolonged survival, (2) a better prognosis with ~synehronous metastases than synchronous, (3) the greater the disease-free interval, the longer ~he survival, (4) no significant difference in suri!yival between resection of solitary metastases !land resection of 2-4 metastases or unilateral vs ~bilateral metastases, and (5) resection of pulmoaary metastases, when indicated, prolonged urvival. Certain criteria for operability must be met n spite of the fact that surgery is the only effecive modality that we have to offer these patients' These are (1) primary disease must be hnder control or controllable, (2) extra)ulmonary disease must be under control or ;ontrollable by surgery, and (3) bilateral multi,le pulmonary metastases must be approaehed ~by staged thoraeotomy or, especially in tumors iwith short doubling times, with median sterinotomy.
i
JUNE 1990 / VOLUME XXXV, NUMBER 6 U R /O L O G Y
Aurora, Colorado 80045-5001 (DR. THRASHER) References 1. Barney JD, and Churchill Ej: AdenocarcinQma of the kidney with metastasis to the lung: cured by nephrectomy and lobectomy, J Uro142:269 (1939). 2. Wflkins EW, Burke JE and Head JM: The surgical management of metastatic neoplasms in the lung, J Thorac Cardiovasc Surg 42:298 (1961). 3. Middleton RG: Surgery for metastatic renal cell carcinoma. J UroI 97:973 (1967). 4. Tolia BM, and Whitmore WF Jr: Solitary metastasis from renal cell carcinoma, J urol 114:836 (1975). 5. O'Dea MJ, Zineke H, Utz DC, and Bernatz PE: The treatment of renal cell carcinoma with solitary metastasis, J Urol 120: 540 (1978). 6. Dernevik L, Berggren H, Larsson S, and Roberts D: Surgieal removal of pulmonary metastases from renal cell carcinoma, Scand J Urol Nephrol 19:133 (1985). 7. Takita H, et al: The surgical management of multiple lung metastases, Ann Thorae Surg 24:359 (1977). 8, Golimbu M, A1-Askari S, Tessler A, and Morales P: Aggressive treatment of metastatic renal cancer, J Urol 136:805 (1986), 9. deKernian JB: Renal tumors, in Walsh PC~ Gittes RF, Perlmutter AD, and Stamey TA (Eds): Campbell's Urology, ed 5, Philadelphia, WB Saunders, 1986, pp 1329-1332
491
