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The aim of the present retrospective analysis was to describe trends in exposure to multiple lines of treatment and survival among 500 metastatic renal cell carcinoma patients who started first-line therapy in 2 different periods (2004-2010 and 2011-2017) in daily practice. Patients who started treatment during the past 5 years received a greater number of treatment lines with an improvement in overall survival.The purpose of the present retrospective analysis was to describe the trends in exposure to multiple lines of treatment and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who started therapy in 2 different periods (period 1, 2004-2010; and period 2, 2011-2017).The proportion of patients who received subsequent lines of treatment after disease progression was compared between the 2 groups. OS was measured from the start of first-line treatment for metastatic disease to death or the last follow-up examination. Both univariate and multivariate analyses were performed.A total of 500 patients were included in the study; 274 started treatment in period 1 and 226 in period 2. Of those patients who stopped first-line treatment because of disease progression, the patients in period 2 had a greater conditional probability to receive second- and third-line treatment compared with patients in period 1 (77.2% vs. 63.7%; odds ratio [OR], 1.93; 95% confidence interval [CI], 1.20-3.11; P = .0065; and 69.6% vs. 48.1%; OR, 2.48; 95% CI, 1.40-4.40; P = .002, respectively). The median OS improved from 22.8 months for patients in period 1 to 38.2 months for patients in period 2 (univariate analysis: hazard ratio, 0.65; 95% CI, 0.50-0.83; P = .001).Patients who started treatment during the past 5 years were exposed to a greater number of treatment lines compared with patients treated before 2011. Our data suggest that the increase of treatment options available and clinician expertise could be associated with better outcomes.