ORLANDO, FL, USA (UroToday.com) - As a counterpoint, Dr. Alexander Kutikov from Fox Chase Cancer Center in Philadelphia was making the case for radical nephrectomy (RN) in elderly patients.
Dr. Kutikov opened by agreeing that PN is an important option for kidney surgeons when treating renal masses. He stated that in the hands of a skilled surgeon, almost all T1 and many of T2 renal masses can be resected with PN. But at the same time, PN is associated with a higher rate of complications, and in patients with complex anatomical lesions, PN has shown a complication rate > 20%. Therefore, in frail and elderly patients with a normal contralateral kidney the use of PN is a critical clinical question that requires a careful risk-benefit analysis before determining the surgery that is most suitable.
Dr. Kutikov went on to show that there is a wide spectrum of patients with renal masses. On one extreme end of the spectrum we have the young patient with an anatomically “simple” mass and a solitary kidney, and this would be an absolute indication for NSS. On the other side, he argued, we have the elderly patient with an anatomically “complex” mass and a normal contralateral kidney, and this is a questionable indication for NSS. RN has shown lower immediate risks while PN has shown potential delayed benefits.
There have been a number of retrospective studies suggesting that PN has advantages over RN, both when it comes to OS and non-cancer specific survival. One systematic review and meta-analysis, from the Mayo Clinic, of PN vs. RN in localized renal tumors included over 40 000 patients from 21 studies, where 77% of patients had RN while 23% had PN. Pooled estimates showed that PN was correlated with a 20% reduced risk for death from all causes and a 30% reduced risk for cancer-specific death. The result for the latter likely represents significant selection bias (removal of the entire kidney cannot be oncologically inferior to removal of just the tumor), and thus puts into question the validity for the conclusions regarding the former.
Dr. Kutikov referenced an editorial from the Journal of Clinical Oncology (JCO) (Korn et al. JCO 2012, 30, 4185) that looked at the potential and limitations of the methodology for comparative effectiveness research. He quoted the editorial by saying that the authors questioned the appropriateness of instrumental variable analyses in clinical cohorts that formed the basis for the Tan et al. manuscript that formed the lynchpin for Dr. Gore’s argument.
After this, Dr. Kutikov referred to a study from their institution, Fox Chase Cancer Center, where they addressed selection bias (J Urol, 2012, 180, 2089). They looked at a SEER-Medicare cohort of T1a renal cell cancer patients undergoing RN vs. PN to see if PN resulted in a durable OS benefit in the Medicare population. The conclusion was that the survival benefit of PN decreases with time and is not significant after 5 years of follow up. This data contradicts usual assumptions of a delayed benefit of PN.
In order to overcome limitations of existing data, two solutions were given by Dr. Kutikov:
- Prospectively measure unmeasured confounders
- Compare groups in prospective randomized fashion
As examples of confounding parameters, he listed age, gender, race, tumor size, tumor anatomic complexity, tumor biology, tumor multifocality, detailed comorbidity data, performance status, history of previous surgery, baseline renal function, and solitary kidney status.
He discussed the EORTC study that showed an unanticipated survival benefit to RN should not be dismissed simply because we don’t like the outcome. Although he pointed out its shortcomings -- such as inadequate accrual, disparities in baseline comorbidities, and crossover between treatment groups -- he noted that findings are provocative and in line with robust donor nephrectomy literature that fails to show any measurable ill effects of RN.
As a conclusion, Dr. Kutikov stressed the importance of the balance of tangible, immediate risks vs. theoretical, delayed benefits. He agreed that for the majority of patients there is no question that PN is the ideal surgical option and RN unnecessarily wastes normal nephron mass, harming a subset of patients. But he also said that “RN in select patients is not a therapeutic ‘sin.'"
In frail elderly patients who do not qualify for active surveillance, using sound clinical judgment is critical.
Presented by Alexander Kutikov, MD at the 2013 Genitourinary Cancers Symposium - February 14 - 16, 2013 - Rosen Shingle Creek - Orlando, Florida USA
Fox Chase Cancer Center, Philadelphia, PA USA
Written by Anna Forsberg, medical reporter for UroToday.com