SAN DIEGO, CA USA (UroToday.com) - In a point/counterpoint plenary debate at the 2013 annual meeting of the AUA moderated by Dr. Michael Jewett (University of Toronto, Canada), Drs. Paul Russo (MSKCC) and Steven Campbell (Cleveland Clinic) argued the merits of partial and radical nephrectomy for the management of cT1b and cT2 renal tumors.
While radical nephrectomy has remained the standard of care for the management of clinically localized RCC for decades, partial nephrectomy is increasingly being utilized with the objective of preserving renal function. Although PN was originally used solely for imperative indications such as the presence of a solitary kidney, the indications have expanded over the past 10-20 years to include patients with a normal contralateral kidney, and PN is oncologically equivalent in the management of cT1a tumors. “The question now is not so much what we are doing about the small tumors, but as they get bigger can we safely perform PN and reap the benefits of renal preservation”? asked Dr. Jewett. An index patient was presented for discussion: a 60 year old Caucasian male with an eGFR of 84 mL/min who is clinically well on statins and has a 5.5 cm left upper pole-enhancing renal mass (cT1bN0M0). CXR was negative for metastatic disease.
Dr. Russo argued that disease-specific survival for cT1a tumors is similar whether patients are treated with PN or RN. In patients undergoing RN, however, Dr. Russo highlighted emerging data on long-term renal functional outcomes and the development of CKD in patients with renal cortical tumors. In an analysis of 662 patients treated with RN or PN, new onset of CKD, as measured by eGFR < 60 mL/min, was less common in patients treated with PN. CKD has been independently evaluated as a risk factor for cardiovascular disease and worse overall survival. “Partial nephrectomy prevents or delays CKD and associated cardiovascular events and mortality,” said Dr. Russo.
An estimated 26 million people in the United States have CKD, and declining GFR is associated with decreased survival. While proponents of RN may argue that patients undergoing transplant donor nephrectomy have not been shown to be at an increased risk of developing CKD, Dr. Russo argued that patients undergoing RN for RCC and organ donation are fundamentally different patients. “The mean pre-operative eGFR in organ donor and RCC patients is 99 versus 69mL/min, so the groups are different.” Performing RN for cT1b and cT2a tumors could result in overtreatment for the 20% of benign lesions identified and place the 5% of patients who develop a contralateral tumor at future risk of renal loss. In data presented from the Mayo clinic, “PN was associated with a 19% reduction in all-cause mortality and a 29% reduction in cancer-specific mortality compared to RN.” In data from the Cleveland Clinic, RN was associated with a 25% increase in cardiovascular deaths, 17% increase in all-cause mortality, and a 3-fold increased risk of CKD. “Patient, tumor, and surgical factors must be considered when deciding between RN and PN.”
Steve Campbell, MD then made the argument for RN by starting with the disclaimer “we still strongly believe in PN for cT1a tumors and whenever preservation of renal function is important,” however “the pendulum has swung too far in the favor of PN.” A recent meta-analysis of 36 studies including > 40 000 patients undergoing PN and RN revealed better renal functional and overall survival outcomes following PN. However, there was a 29% improvement in cancer-specific survival in patients treated with PN. “Certainly partial nephrectomy is a great procedure, but it cannot be a stronger oncologic operation than radical nephrectomy, and this highlights the selection bias inherent to all retrospective studies,” said Dr. Campbell.
“There is one randomized controlled trial that has addressed this question.” EORTC 30904 randomized 268 and 273 patients to PN and RN, respectively. RN was associated with less morbidity, and PN with better renal function, but 10-year overall survival was greater for RN (81% vs. 76%, p=0.03). Cardiovascular disease was the most common cause of death and occurred more commonly in patients undergoing PN (n=25 PN, 20 RN). This trial illustrates that the “functional advantage related to PN may not be as beneficial as we previously thought.” One explanation could stem from the difference between medical (CKD-M) and surgical (CKD-S) CKD. In 4 180 patients treated with RN or PN (1100 CKD-M, 900 CKD-S), the rate of annual decline in renal function was measured, and a decline >4% annually was associated with a 43% increased risk of mortality (p < 0.0001). CKD-S is more stable, and may have less impact on survival. Following RN and PN, the survival of patients with CKD-S is equivalent to patients with no CKD, whereas CKD-M is associated with worse survival. In the presence of a normal contralateral kidney, PN may not provide a survival advantage compared to RN. “We should not perform any borderline heroic partial nephrectomies in patients with a normal contralateral kidney, and we are currently organizing a randomized trial of PN and RN for cT1b to cT2a renal masses.”
In summary, PN remains the standard of care for cT1a RCC, and PN should be considered in larger tumors when renal function is impaired. Tumor stage (size) is not the only tumor factor to consider for technical feasibility. There is a lack of high-level evidence for the superiority of PN or RN. With normal preoperative renal function and a normal contralateral kidney, RN should be considered.
Presented by Michael A.S. Jewett, MD, Paul Russo, MD, and Steven Charles Campbell, MD, PhD at the American Urological Association (AUA) Annual Meeting - May 4 - 8, 2013 - San Diego Convention Center - San Diego, California USA
Reported for UroToday.com by Jeffrey J. Tomaszewski, MD