Survival outcomes for advanced kidney cancer patients in the era of targeted therapies.

Background: Advanced renal cell carcinoma (RCC) results in over 14,000 deaths each year in the United States alone. The therapeutic landscape for advanced RCC changed dramatically with the approval of tyrosine kinase inhibitors (TKI) between 2006 and 2012. A large-scale analysis of survival trends has not been performed in the TKI era to determine their impact on outcomes for advanced RCC patients.

Methods: The Surveillance, Epidemiology and End-Results (SEER) database was queried for adult patients with advanced RCC diagnosed between 2000 and 2013. Patients were divided into two cohorts based on the year of diagnosis-pre-TKI cohort [2000-2006] and TKI cohort [2007-2013]. Kaplan-Meier survival and multivariate Cox proportional hazards analyses were performed.

Results: A total of 14,976 patients were included in our study. Median age at diagnosis was 64 years (range, 18-89 years). Median (cancer-specific) overall survival was 10.0 months in the TKI cohort compared with 8.0 months in the pre-TKI cohort, corresponding to a 13% improvement in survival in the TKI area [hazard ratio (HR) for death 0.87; 95% confidence interval (CI), 0.84-0.91, P<0.0001]. Median survival was improved by 2 months for patients with clear-cell RCC histology [HR for death 0.86; 95% CI, 0.84-0.91, P<0.0001]. Patients with non-clear cell RCC had a 25% higher risk of mortality compared with those with clear-cell RCC. Additionally, median survival for non-clear cell RCC patients was not statistically different between the two cohorts (HR for death 0.98; 95% CI, 0.88-1.09, P=0.714). Subgroup analysis showed that elderly patients (age 71 years and above) had a 45% higher risk of death from advanced RCC compared with young patients (aged 18-50 years) [HR for death 1.45; 95% CI, 1.36-1.54, P<0.0001]. Gender and racial disparities in outcomes were also noted with women having a 10% higher risk of death compared with men (HR for death 1.10; 95% CI, 1.06-1.14, P<0.001) and Black patients having a 15% higher risk of death compared with White patients (HR for death 1.15; 95% CI, 1.08-1.23, P<0.0001).

Conclusions: Our study provides a largest registry-based analysis of survival outcomes in the TKI era. In majority of patients, the survival has improved significantly with the advent of TKIs as standard of care therapy. Survival for patients with non-clear cell RCC is clearly worse than clear-cell RCC and does not appear to have changed with TKIs. Elderly patients, women, and Black patients appear to have worse outcomes and these disparities merit further investigation.