Mortality trends and the impact of lymphadenectomy on survival for renal cell carcinoma patients with distant metastasis

Introduction: Current treatment paradigms for metastatic renal cell carcinoma (mRCC) invoke a combination of surgical and systemic therapies. We sought to quantify trends in mortality and performance of lymphadenectomy, as well as impact on survival for patients with mRCC. Methods: The Surveillance, Epidemiology, and End Results registry (SEER) (1988-2011) identified patients with mRCC. Kaplan-Meier curves and Cox proportional hazards models with competing risks regression were employed to assess survival. Results: 15 060 patients with mRCC were identified, with 6316 (41.9%) undergoing cytoreductive nephrectomy. Mean number of lymph nodes removed was 6.2, with mean 3.3 positive nodes among 1018 (43.9%) patients with positive nodes. Median overall survival (OS) increased from seven to 11 months (1999-2010), and finding a positive node decreased median cancer survival from 22 to nine months. Cancer-specific survival (CSS) showed significant decreases in mortality after 2005 (hazard ratio [HR] 0.71 [0.60?0.83] comparing 2010 to 1990). Lymphadenectomy was associated with decreased OS (HR 1.10 [1.03-1.16]; p=0.002) due to decreased CSS (HR 1.10 [1.04-1.17]; p<0.001) without increase in other-cause mortality (HR 0.94 [0.79-1.11]; p=0.455). However, more extensive lymphadenectomy ≥3 lymph nodes removed did not significantly impact OS or CSS. Number of positive lymph nodes was associated with decreased CSS. Conclusions: mRCC continues to carry a poor prognosis, but current treatment paradigms have led to modest improvements in OS and CSS in recent years. Lymphadenectomy was found to play a prognostic rather than therapeutic role in the management of mRCC. The performance of lymphadenectomy should be limited based on clinical judgment and better incorporated into randomized trials of new systemic therapies to identify scenarios where implementation may improve survival.