Survival trends of men and women with metastatic clear cell renal cell carcinoma.

4566 Background: Clear cell renal cell carcinoma (ccRCC) is nearly twice as common in men as in women, and women with non-metastatic RCC have a better prognosis than men. The etiology for these disparities is not known, though sex-specific differences in risk factor prevalence and tumor biology have been reported. The differential impact of systemic therapies, including tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), on prognosis in women and men with metastatic ccRCC is not defined. Methods: Clinicopathologic features and survival of patients with clinical stage IV ccRCC were obtained from the National Cancer Database (NCDB). Patients were grouped by date of metastatic diagnosis into three eras that correspond to major advances in systemic therapy: 2004-2005 (pre-TKI), 2006-2014 (TKI), and 2015-2016 (ICI). Uni- and multi-variable chi-square, logistic regression, and survival analyses were used for comparisons. Survival differences were assessed using Kaplan-Meier curves. Results: 15,025 male and 7,100 female patients with metastatic ccRCC were identified. Demographic features were similar between cohorts though females were slightly older (median 64.8 vs 62.7 mo, p < 0.0001), more likely to be black (6.5% vs 6.0%, p = 0.0119) or receiving Medicare benefits (46.4% vs 39.9%, p < 0.0001). In the combined cohort, median overall survival (OS) was higher in patients diagnosed in the ICI vs TKI (23.0 vs 16.5 mo) and pre-TKI eras (14.4 mo, log-rank p < 0.0001). Compared with men of the same age groups, OS was inferior for women age 50-64 yr (median 18.4 vs 21.1mo, p = 0.0084) and > 64 yr (15.3 vs 12.6mo, p = 0.0001), but not < 50 yr (20.3 vs 21.7mo, p = 0.6290). In the ICI era, median OS improved by a lesser absolute but similar relative amount for women compared to men (+5.6mo [+39%] and +7.2mo [+41%]), respectively). After controlling for age, race, Charlson-Deyo score, initial treatment modality, and insurance and socioeconomic status, women remained at increased risk of death in both the ICI era (HR 1.12 [95% CI 1.04-1.22], p = 0.004) and the TKI era (HR 1.08 [1.04-1.12], p < 0.001). Conclusions: Women with metastatic ccRCC have a worse prognosis than men which is not explained by demographic differences. This disparity is observed in both the TKI and ICI eras. This finding contrasts with previous studies suggesting women with localized RCC have a favorable prognosis compared with men. Further investigation into the sex-specific biology of metastatic ccRCC is warranted.