Urological Survey Urological Oncology: Adrenal, Renal, Ureteral and Retroperitoneal Tumors Re: Overall Survival Advantage with Partial Nephrectomy: A Bias of Observational Data? B. Shuch, J. Hanley, J. Lai, S. Vourganti, S. P. Kim, C. M. Setodji, A. W. Dick, W. H. Chow and C. Saigal; Urologic Diseases in America Project Department of Urology, Yale School of Medicine, New Haven, Connecticut, and Urologic Oncology Branch, National Cancer Institute, Bethesda, Maryland Cancer 2013; 119: 2981e2989.
Abstract available at http://jurology.com/ Editorial Comment: The long-term results of the EORTC (European Organization for the Research and Treatment of Cancer) randomized clinical trial 30094 challenge the concept that partial nephrectomy (PN) results in better overall survival than radical nephrectomy (RN) in renal cell carcinoma (RCC). In truth this concept is mainly based on retrospective studies, which are not without biases. It is also true that the EORTC trial is not exempt from critics, even though it represents the highest current level of evidence. The authors hypothesized that if RN worsened overall survival compared to PN, survival would be worse than in controls, and similarly if improvement in overall survival with PN were due to selection bias, survival would be improved compared to controls. Using the SEER (Surveillance, Epidemiology and End Results) database, they compared individuals 66 years old or older diagnosed with RCC between 1992 and 2007 treated with radical or partial nephrectomy with separate cancer (nonmuscle invasive bladder cancer) and noncancer controls to minimize nonmeasurable differences between individuals with and without cancer. Matched samples were well balanced for age, year of diagnosis, race, gender, Charlson comorbidity index and preexisting hypertension. Median overall survival following PN was significantly higher than in controls without cancer or with nonmuscle invasive bladder cancer, while median overall survival after RN was similar among the 3 groups, confirming the hypothesis that selection bias may be present in observational data and that RN may be less harmful than previously believed. Studies questioning the current knowledge should not be disregarded, but carefully scrutinized. The matter of overall survival after partial or radical nephrectomy remains controversial. Others have conducted exhaustive analyses directed at minimizing the bias of using the SEER database with different results than the present ones. The RCC cohort included in this study might not represent in terms of age and comorbidity the profile of a substantial percentage of patients. Renal function was not considered in the present study. Despite some hints indicating that surgically induced chronic kidney disease (CKD) is not as severe as medically driven CKD, it seems logical that any degree of surgically induced CKD will only worsen medical CKD. For the time being it would be wise to remember that, if necessary, RN may provide a definitive curative option for some healthy elderly patients without detrimental effect on their overall survival, although PN remains the standard of care for small renal masses. M. Pilar Laguna, MD, PhD
0022-5347/14/1912-0346/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
346
j
www.jurology.com
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.10.090 Vol. 191, 346-349, February 2014 Printed in U.S.A.
ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
Suggested Reading Weight CJ, Miller DC, Campbell SC et al: The management of a clinical T1b renal tumor in the presence of a normal contralateral kidney. J Urol 2013; 189: 1198. Tan HJ, Hafez KS, Ye Z et al: Postoperative complications and long-term survival among patients treated surgically for renal cell carcinoma. J Urol 2012; 187: 60.
Re: Parenchymal Volume Preservation and Ischemia during Partial Nephrectomy: Functional and Volumetric Analysis M. C. Mir, R. A. Campbell, N. Sharma, E. M. Remer, J. Li, S. Demirjian, J. Kaouk and S. C. Campbell Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio Urology 2013; 82: 263e268.
Abstract available at http://jurology.com/ Editorial Comment: With the increasing diagnosis of small renal masses and use of partial nephrectomy, a new debate has arisen. Does the fate of postoperative renal function depend on ischemia time or on the amount of parenchyma preserved? This rapid communication based on retrospective data from 93 patients supports the superiority of amount of functional parenchyma preserved over ischemia time in renal function preservation. Median parenchyma volume saved and estimated glomerular filtration rate (eGFR) preserved were 83% and 79%, respectively, and did not substantially differ between cases with a solitary and a normal contralateral kidney. Percent eGFR preserved was strongly associated with percent parenchyma volume saved and lower complexity tumors. It was not associated with ischemia time. One should not be misled into thinking that this lack of correlation between ischemia time and postoperative eGFR means that ischemia time is unimportant. Selection bias and population heterogeneity may weaken the results of the study. In fact, a positive correlation between the use of hypothermia and percent eGFR preserved was found, in that patients operated on under renal hypothermia recovered more than 80% of renal function despite longer median ischemia times, while only 19% of the warm ischemia group recovered more than 80% of renal function. This finding suggests the latter group had some difficulties in recovering from the ischemic insult and that hypothermia compensates for longer ischemia times. As the difference in median times between warm and cold ischemia was 7 minutes, and cold ischemia never exceeded 31 minutes in any case, the range in time seems too narrow to extract any definitive conclusion. We fully agree with the authors that maximal parenchyma volume preservation is a primary objective of partial nephrectomy, especially now that 1 mm healthy parenchyma around the tumor is enough to pronounce negative margins. However, minimizing ischemia time should not be neglected, but should be considered a coprimary objective. There is even a third player in the game, ie quality of the preexisting parenchyma. The worse the preexisting renal function, the greater our efforts should be to preserve maximum parenchyma and to minimize ischemia time. M. Pilar Laguna, MD, PhD
Suggested Reading Aron M, Gill IS and Campbell SC: A nonischemic approach to partial nephrectomy is optimal. J Urol 2012; 187: 387. Lane BR, Russo P, Uzzo RG et al: Comparison of cold and warm ischemia during partial nephrectomy in 660 solitary kidneys reveals predominant role of nonmodifiable factors in determining ultimate renal function. J Urol 2011; 185: 421. Simmons MN, Fergany AF and Campbell SC: Effect of parenchymal volume preservation on kidney function after partial nephrectomy. J Urol 2011; 186: 405. Yossepowitch O, Eggener SE, Serio A et al: Temporary renal ischemia during nephron sparing surgery is associated with short-term but not long-term impairment in renal function. J Urol 2006; 176: 1339.
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Abstract available at http://jurology.com/ Editorial Comment: The long-term results of the EORTC (European Organization for the Research and Treatment of Cancer) randomized clinical trial 30094 challenge the concept that partial nephrectomy (PN) results in better overall survival than radical nephrectomy (RN) in renal cell carcinoma (RCC). In truth this concept is mainly based on retrospective studies, which are not without biases. It is also true that the EORTC trial is not exempt from critics, even though it represents the highest current level of evidence. The authors hypothesized that if RN worsened overall survival compared to PN, survival would be worse than in controls, and similarly if improvement in overall survival with PN were due to selection bias, survival would be improved compared to controls. Using the SEER (Surveillance, Epidemiology and End Results) database, they compared individuals 66 years old or older diagnosed with RCC between 1992 and 2007 treated with radical or partial nephrectomy with separate cancer (nonmuscle invasive bladder cancer) and noncancer controls to minimize nonmeasurable differences between individuals with and without cancer. Matched samples were well balanced for age, year of diagnosis, race, gender, Charlson comorbidity index and preexisting hypertension. Median overall survival following PN was significantly higher than in controls without cancer or with nonmuscle invasive bladder cancer, while median overall survival after RN was similar among the 3 groups, confirming the hypothesis that selection bias may be present in observational data and that RN may be less harmful than previously believed. Studies questioning the current knowledge should not be disregarded, but carefully scrutinized. The matter of overall survival after partial or radical nephrectomy remains controversial. Others have conducted exhaustive analyses directed at minimizing the bias of using the SEER database with different results than the present ones. The RCC cohort included in this study might not represent in terms of age and comorbidity the profile of a substantial percentage of patients. Renal function was not considered in the present study. Despite some hints indicating that surgically induced chronic kidney disease (CKD) is not as severe as medically driven CKD, it seems logical that any degree of surgically induced CKD will only worsen medical CKD. For the time being it would be wise to remember that, if necessary, RN may provide a definitive curative option for some healthy elderly patients without detrimental effect on their overall survival, although PN remains the standard of care for small renal masses. M. Pilar Laguna, MD, PhD
0022-5347/14/1912-0346/0 THE JOURNAL OF UROLOGY® © 2014 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
346
j
www.jurology.com
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2013.10.090 Vol. 191, 346-349, February 2014 Printed in U.S.A.
ADRENAL, RENAL, URETERAL AND RETROPERITONEAL TUMORS
Suggested Reading Weight CJ, Miller DC, Campbell SC et al: The management of a clinical T1b renal tumor in the presence of a normal contralateral kidney. J Urol 2013; 189: 1198. Tan HJ, Hafez KS, Ye Z et al: Postoperative complications and long-term survival among patients treated surgically for renal cell carcinoma. J Urol 2012; 187: 60.
Re: Parenchymal Volume Preservation and Ischemia during Partial Nephrectomy: Functional and Volumetric Analysis M. C. Mir, R. A. Campbell, N. Sharma, E. M. Remer, J. Li, S. Demirjian, J. Kaouk and S. C. Campbell Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio Urology 2013; 82: 263e268.
Abstract available at http://jurology.com/ Editorial Comment: With the increasing diagnosis of small renal masses and use of partial nephrectomy, a new debate has arisen. Does the fate of postoperative renal function depend on ischemia time or on the amount of parenchyma preserved? This rapid communication based on retrospective data from 93 patients supports the superiority of amount of functional parenchyma preserved over ischemia time in renal function preservation. Median parenchyma volume saved and estimated glomerular filtration rate (eGFR) preserved were 83% and 79%, respectively, and did not substantially differ between cases with a solitary and a normal contralateral kidney. Percent eGFR preserved was strongly associated with percent parenchyma volume saved and lower complexity tumors. It was not associated with ischemia time. One should not be misled into thinking that this lack of correlation between ischemia time and postoperative eGFR means that ischemia time is unimportant. Selection bias and population heterogeneity may weaken the results of the study. In fact, a positive correlation between the use of hypothermia and percent eGFR preserved was found, in that patients operated on under renal hypothermia recovered more than 80% of renal function despite longer median ischemia times, while only 19% of the warm ischemia group recovered more than 80% of renal function. This finding suggests the latter group had some difficulties in recovering from the ischemic insult and that hypothermia compensates for longer ischemia times. As the difference in median times between warm and cold ischemia was 7 minutes, and cold ischemia never exceeded 31 minutes in any case, the range in time seems too narrow to extract any definitive conclusion. We fully agree with the authors that maximal parenchyma volume preservation is a primary objective of partial nephrectomy, especially now that 1 mm healthy parenchyma around the tumor is enough to pronounce negative margins. However, minimizing ischemia time should not be neglected, but should be considered a coprimary objective. There is even a third player in the game, ie quality of the preexisting parenchyma. The worse the preexisting renal function, the greater our efforts should be to preserve maximum parenchyma and to minimize ischemia time. M. Pilar Laguna, MD, PhD
Suggested Reading Aron M, Gill IS and Campbell SC: A nonischemic approach to partial nephrectomy is optimal. J Urol 2012; 187: 387. Lane BR, Russo P, Uzzo RG et al: Comparison of cold and warm ischemia during partial nephrectomy in 660 solitary kidneys reveals predominant role of nonmodifiable factors in determining ultimate renal function. J Urol 2011; 185: 421. Simmons MN, Fergany AF and Campbell SC: Effect of parenchymal volume preservation on kidney function after partial nephrectomy. J Urol 2011; 186: 405. Yossepowitch O, Eggener SE, Serio A et al: Temporary renal ischemia during nephron sparing surgery is associated with short-term but not long-term impairment in renal function. J Urol 2006; 176: 1339.
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