Survival in patients with renal cell carcinoma and brain metastases: an update of the Renal Graded Prognostic Assessment.
Abstract
Background
Brain metastases are a common and serious consequence for patients with renal cell carcinoma. This study aimed to determine if survival has changed since the introduction of current therapies, identify prognostic factors, update the prognostic index (the Renal Graded Prognostic Assessment [GPA]) in the context of contemporary multi-modal therapies, compare outcomes with legacy cohorts, and determine whether overall survival correlates with intracranial progression-free survival.
Methods
An international consortium of 21 academic institutions contributed uniformly-curated retrospective data from 1049 patients with newly-diagnosed renal cell carcinoma with brain metastases (RCC-BM) treated between Jan 1, 2016, and Dec 31, 2022. Patients treated between 1985-2007 (n=286) and 2006-15 (n=711) were considered legacy cohorts and compared to the current cohort. Significant prognostic factors for survival were identified through combined multivariable analyses and used to update the Renal GPA. Intracranial progression-free survival was defined as the interval from date of initial RCC-BM diagnosis to date of first salvage treatment.
Findings
Of the 1049 patients, 773 (73·7%) patients were male and 276 (26·3%) were female; the majority (851 [81·1%]) were White, and the median age was 63·9 years (IQR 56·2-70·3). The median overall survival was 20·0 months (95% CI 18·0-23·4), with a median follow-up of 53·4 months (95% CI 50·2-56·8). Overall survival for the legacy cohorts were 9·6 months (95% CI 8-11) and 12·0 months (5-11), respectively. In combined multivariable analyses, significant prognostic factors for inferior survival 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 survival 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 1·5-2·0, 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 progression-free survival and overall survival was moderately strong (0·74 [95% CI 0·70-0·78]; p<0·0001).
Interpretation
Survival has improved compared to the legacy cohorts but varies widely by GPA. The updated Renal GPA can be used to estimate survival, intracranial progression-free survival, individualise treatment, design and stratify clinical trials, and refine clinical trial eligibility.
Funding
US National Institutes of Health (NCI P30CA014236), the Duke Center for Brain and Spine Metastases.