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Surgical therapy is the gold standard treatment for renal cell carcinoma (RCC), offering long-term cure in patients with localized disease and reasonable cancer control in patients with locally advanced disease. According to current guideline recommendations, radical nephrectomy (RN) is no longer the standard of care for low-stage RCC (T1). These patients should undergo nephron-sparing surgery (NSS) whenever possible (1). There is a good level of evidence from prospectively randomized clinical trials that both RN and NSS provide excellent oncologic results (2). In addition, there is increasing evidence that chronic renal insufficiency induced by RN is associated with an increased risk for cardiovascular events and finally an increased death rate from any cause compared with NSS (3). However, the majority of previous studies were limited due to their retrospective design. To further elucidate the impact of surgery on renal deterioration and to achieve the highest level of evidence, the European Organisation for Research and Treatment of Cancer (EORTC) set out analyzing this issue in a prospective randomized controlled trial.
The results of the EORTC 30904 trial were recently published by Scosyrev et al. (4). Between 1992 and 2003, in total 273 patients were randomized to RN and 268 patients were randomized to NSS. Finally, 259 and 255 patients after RN and NSS, respectively, had a recorded postoperative estimated glomerular filtration rate (eGFR) and were included in the analyses. The authors found that compared with RN, NSS reduced the incidence of moderate renal dysfunction (eGFR <60 mL/min and <45 mL/min) at a significant margin. Interestingly, the incidence of advanced kidney disease (eGFR <30 mL/min) and the incidence of kidney failure (eGFR <15 mL/min) were relatively similar in both treatment arms. Moreover, the positive impact of NSS on eGFR did not translate into improved survival in this study population. Nevertheless, the results of this study clearly underscore the importance of NSS on renal function preservation. Interpreting the outcome results, it is important to notice that this noninferiority trial was underpowered due to premature closure because of poor accrual. Thus, while the debate regarding renal function may end with these results, the survival controversy continues (5).
Modern oncological therapies may provide more than oncological safety. In the last decade, minimally invasive techniques in renal surgery have increasingly become a desired approach for NSS, as they may decrease patient morbidity compared with open procedures. Comparable to other urological tumour entities such as prostate cancer, for NSS the triple goals of negative surgical margins, functional preservation, and complication-free recovery have been summarized as the TRIFECTA criteria (6). The second selected study by Minervini et al. (7) describes the results of a 4-year, prospective, observational, multicentre study (time of enrollment: January 2009 – January 2011) analyzing clinical, surgical, pathologic, functional results, and TRIFECTA (defined as warm ischemia time <25 min, negative surgical margins, and no perioperative complications) outcomes with regard to the open or laparoscopic surgical approach. The analyses based on results of 450 of 554 patients who underwent open (n=301) or laparoscopic (n=149) NSS for clinical T1a RCC. After propensity score matching for preoperative variables, the authors found no significant difference in achieving the TRIFECTA outcome between open and laparoscopic NSS. Importantly, the open approach was associated with a significantly shorter warm ischemia time, although the number of more complex tumours (mainly or complete endophytic) was higher in this subgroup of patients. Nevertheless, eGFR at 6-month follow-up did not differ significantly between both surgical approaches. While previous studies challenged the role of laparoscopic NSS (8), the results of this prospective endeavour suggest that both approaches can equally be offered. Important to notice is the lack of randomization as well as the shortterm follow-up limiting the strength of these findings. There is no doubt that the surgeons' experience is of critical importance, and thus adjustment for the institutional and surgeons' caseload would have been desirable. Nevertheless, with this publication, the evidence is continuously growing that a more precise patient selection is essential in low-stage RCC to counsel for the surgical approach, but the open procedure remains the mainstay for complex small tumours.