Saturday, October 11, 2014

Who Really Benefits From Nephron-Sparing Surgery?

In the last 15 years, new information has fundamentally changed our approach to the management of renal masses. Previously, all renal masses, regardless of size, in the presence of a normal contralateral kidney were managed by radical nephrectomy (RN). The fundamental belief then was that this was akin to kidney donation for transplantation. Now we know that young, healthy, and carefully selected kidney donors sit in contradistinction to most sporadic renal tumor patients, who are 25 years older, and many of whom suffer from common medical comorbidities that affect renal function, including hypertension, diabetes, obesity, and cigarette smoking–induced vascular disease.1
The recent understanding that chronic kidney disease (CKD)—renal function below an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m2 but above that of end-stage renal disease (<15 mL/min/1.73 m2)—is associated with cardiovascular morbidity and mortality2 has led to many studies evaluating whether nephrectomy for renal masses induces similar adverse renal functional and cardiovascular events. Although most studies, such as this one, are retrospective reviews of institutional or multi-institutional databases and are subject to all of the usual weaknesses of such studies, key observations have been consistently made. First, up to 30% of patients with renal tumors have preexisting CKD (stage 3 or worse), even if their serum creatinine is within normal limits. Second, partial nephrectomy (PN) effectively prevents or delays the onset of CKD and is associated with less cardiovascular morbidity and better overall survival.3-7
As demonstrated by Woldu and colleagues, within their pool of patients undergoing renal tumor surgery from 1992 to 2012, there is a range of presurgical renal function, yet the majority (80%) had eGFR >60 mL/min/1.73 m2 (CKD stage 1 and 2, considered "normal" by most nephrologists), and 20.1% had an eGFR <60 mL/min/1.73 m2 (CKD stage 3).The authors report that PN was associated with a significantly lower rate of annual eGFR decline in patients with a starting eGFR >60 mL/min/1.73 m2, but not in patients with a starting eGFR <60 mL/min/1.73 m2. The group at the greatest risk for developing "significant" renal impairment (defined as eGFR <45 mL/min/1.73 m2 or 30 mL/min/1.73 m2) was restricted to those with CKD stage 2 (eGFR between 60 and 89 mL/min/1.73 m2).
Certain factors in this dataset could influence these results. The study covers a 20-year period. Initially PN was used sparingly (18.8%); however, PN became the predominant procedure (53.6%) in the latter part of the study as the surgeons became more comfortable executing this complex operation. Many unaccounted for technical factors, including estimated blood loss, intraoperative hypotension, ischemia type (ie, warm, cold, or none), percentage of kidney preserved, and degree of surgical difficulty (nephrometry) could also influence these results. Notably, higher-stage tumors were treated with RN across the board. Assuming that these higher-stage tumors were larger, the possibility of contralateral renal compensation leading to a greater renal reserve and lesser impact of RN exists.
Despite the limitations implicit in this kind of surgical research, this study and others like it clearly indicate that kidney preservation for the management of renal masses is now front and center in contemporary urology. For healthy patients with excellent preexisting kidney function, the impact of PN on overall renal function may not be as great as in patients with moderate to severe preexisting renal impairment. All groups benefit from the equivalent local tumor control of PN to RN, with the added benefit of facing the low but real possibility of a contralateral tumor in their lifetime with much more than a solitary kidney. For elderly, comorbidly ill, and otherwise vulnerable patients with small renal masses, the other rational approach to kidney preservation is active surveillance, with only rare patients outliving their medical problems to experience significant renal cancer progression.8
References
  1. Russo P. The role of surgery in the management of early-stage renal cancer. Hematol Oncol Clin North Am2011;25(4):737-752.http://www.hemonc.theclinics.com/article/S0889-8588%2811%2900051-7/abstract
  2. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Eng J Med. 2004;351(13):1296-1305. http://www.nejm.org/doi/full/10.1056/NEJMoa041031
  3. Huang WC, Levey AS, Serio AM, et al. Chronic kidney disease after nephrectomy in patients with renal cortical tumors: a retrospective cohort study. Lancet Oncol. 2006;7(9):735-740.http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970803-8/abstract
  4. Thompson HR, Boorjian SA, Lohse CM, et al. Radical nephrectomy for pT1a renal masses may be associated with decreased overall survival compared to partial nephrectomy. J Urol. 2008;179(2):468-473.http://www.urosa.co.za/images/RadicalNephrectomyT1aRenalmassesOverall.pdf
  5. Huang WC, Elkin EB, Levey AS, et al. Partial nephrectomy versus radical nephrectomy in patients with small renal tumors–is there a difference in mortality and cardiovascular outcomes. J Urol. 2009;181(1):55-62.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748741/
  6. Tan HJ, Norton EC, Ye Z, et al. Long-term survival following partial vs. radical nephrectomy among older patients with early-stage kidney cancer. JAMA. 2012;307(15):1629-1635. http://jama.jamanetwork.com/article.aspx?articleid=1148150
  7. Kim SP, Thompson H, Boorjian SA, et al. Comparative effectiveness for survival and renal function of partial and radical nephrectomy for localized renal tumors: A systematic review and meta-analysis. J Urol. 2012;188(1):51-57.http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0049517/
  8. Jewett MAS, Zuniga A. Renal tumor natural history: The rationale and role for active surveillance. Urol Clin North Am. 2008;35(4):627-634.http://www.urologic.theclinics.com/article/S0094-0143%2808%2900059-1/abstract


Urology
Who Really Benefits From Nephron-Sparing Surgery?
Urology 2014 Oct 01;84(4)860-868, SL Woldu, AC Weinberg, R Korets, R Ghandour, MR Danzig, A RoyChoudhury, SD Kalloo, MC Benson, GJ DeCastro, JM McKiernan

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