Survival of patients with renal cell carcinoma and brain metastases: update of the Renal Graded Prognostic Assessment

Brain metastases (BMs) are a common and serious consequence for patients with renal cell carcinoma (RCC). An international consortium of 21 institutions aimed to determine if survival has changed since the introduction of current therapies and to update the prognostic index (the Renal Graded Prognostic Assessment; GPA). The study included uniformly-curated retrospective data from 1049 patients withnewly-diagnosed RCC with BMs treated between 2016 and 2022. Patients treated between 1985-2007 (n=286) and 2006-2015 (n=711) were considered legacy cohorts and compared to the current cohort. Among the 1049 patients, the median overall survival (OS) was 20.0 months (95% CI 18.0-23.4). Median OS for the legacy cohorts was 9.6 months and 12.0 months, respectively. In combined multivariable analyses, significant prognostic factors for inferior OS were lower Karnofsky Performance Status, lower baseline serum albumin, higher number of brain metastases, and presence of extracranial metastases. These factors were incorporated into the updated Renal GPA. Median OS was 4.8 months (95% CI 3.0-8.1) for patients with GPA 0-1.0; 12.4 months (10.6-17.2) for GPA 2.5-2.0; 33.6 months (27.5-40.0) for GPA 2.5-3.0; and 51.2 months (34.1-undefined) for GPA 3.5-4.0). Median intracranial progression-free survival was 9.6 months (95% CI 8.4-10.6). The Spearman’s rank correlation between intracranial PFS and OS was moderately strong (0.74; p<0.0001). The authors conclude that survival has improved compared to the legacy cohorts but varies widely by GPA.