Survival of metastatic renal cell carcinoma patients continues to improve over time, even in targeted therapy era

Objective: To examine the effect of diagnosis year, defined as contemporary (2010–2014), intermediate (2006–2009) and historical (2001–2005) on cancer-specific mortality (CSM) in patients with metastatic renal cell carcinoma (mRCC). Methods: Within Surveillance, Epidemiology, and End Results registry (2001–2014), we identified patients with mRCC. Cumulative incidence and competing risks regression (CRR) models examined CSM, after accounting for other-cause mortality. Finally, we performed subgroup analyses according to histological subtype: clear-cell mRCC (ccmRCC) versus non-ccmRCC. Results: We identified 15,444 patients with mRCC. Of those, 41.0, 28.7 and 30.3% were diagnosed, respectively, in the contemporary, intermediate and historical years. Of all, 47.1, 5.3 and 47.6% were, respectively, ccmRCC, non-ccmRCC and other mRCC histological variants [sarcomatoid mRCC, cyst-associated mRCC, collecting duct carcinoma and mRCC not otherwise specified (NOS)]. Overall, 24-month CSM rates were, respectively, 61.0, 63.7 and 67.3% in contemporary, intermediate and historical patients. In all patients, multivariable CRR models exhibited higher CSM in intermediate (HR 1.11; p < 0.001) and historical patients (HR 1.24; p < 0.001) than in contemporary patients. Multivariable CRR models focusing on ccmRCC yielded virtually the same results. However, multivariable CRR models focusing on non-ccmRCC showed no CSM differences according to diagnosis year (all p ≥ 0.3). Conclusion: The introduction of new therapeutic agents resulted in CSM-free survival improvement over study time. However, this effect exclusively applies to patients with ccmRCC, but not to those with non-ccmRCC. This observation is in agreement with established efficacy of systemic therapies for ccmRCC, but lesser efficacy of these agents for non-ccmRCC.