Disease-Specific Survival in De Novo Metastatic Renal Cell Carcinoma in the Cytokine and Targeted Therapy Era

BACKGROUND: Recent phase III studies of targeted agents for metastatic renal cell carcinoma (mRCC) have generated median survival estimates that far exceed those observed during the cytokine era. However, substantial population-based data does not exist to confirm this trend. We sought to determine whether survival has improved for patients with mRCC diagnosed in the era of targeted therapies, as compared to the era of immunotherapy. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Registry was used to identify patients aged 18 and older diagnosed stage IV RCC between 1992 and 2009. Patients had documented clear cell, papillary or chromophobe histology. The Kaplan Meier method and log-rank test were used to compare disease-specific survival (DSS) for patients diagnosed from 1992–2004 (i.e., the cytokine era) and 2005–2009 (i.e., the targeted therapy era). Univariate and multivariate analyses of relevant clinicopathologic characteristics were also performed. RESULTS: Of 5,176 patients identified using the above characteristics, 2,392 patients were diagnosed from 1992–2004 and 2,784 from 2005–2009. Median DSS was improved in those patients diagnosed from 2005–2009 (16 months vs 13 months; P<0.0001). A similar temporal trend towards improving survival was noted in patients with clear cell (P = 0.0006), but not in patients with non-clear cell disease (P = 0.32). Notable findings on multivariate analysis include an association between shorter DSS and the following characteristics: (1) diagnosis from 1992–2004, (2) advanced age (80+), and (3) absence of cytoreductive nephrectomy. CONCLUSIONS: These data reflect progress in the management of mRCC, specifically in the era of targeted therapies. Notably, it was inferred that certain treatment strategies were employed during pre-specified time periods, representing a major caveat of the current analysis. Further studies related to the influence of age and race/ethnicity are warranted, as are studies exploring the role of cytoreductive nephrectomy and novel treatments for non-clear cell disease.