Survival of patients with metastatic renal cell carcinoma with or without brain metastases.

476 Background: Brain metastasis (BM) is an adverse prognostic indicator and associated with poor survival for patients with metastatic renal cell carcinoma (mRCC). Although immune checkpoint inhibitor (ICI) therapy has significantly improved survival in patients with metastatic renal cell carcinoma, the prognostic significance of BM in the ICI era is unclear. Methods: We performed a retrospective cohort study of patients diagnosed with clear cell RCC (ccRCC) between 2012-2023 at the Yale Cancer Center. We examined the association between brain metastasis and overall survival among patients by treatment type (with or without ICI in any line of therapy). We compared overall survival (mOS) using Kaplan-Meier analyses and multivariable Cox proportional hazards models. Results: We identified 338 patients diagnosed with metastatic ccRCC between 2012 and 2023, of whom 96 (28.4%) had BM, 39 of which were detected by screening versus 57 detected by symptoms. BM detected on screening MRI were smaller than those identified for cause (mean 13.9 versus 20.8 mm, respectively, p=0.002). The mOS from the time of metastatic ccRCC diagnosis was 54.0 months (95%CI 41-76) in patients without BM versus 37.0 (27-52) months in patients with BM (p=0.03). Among patients who received ICI therapy, mOS was 66 months (95% CI, 50-91) in those without BM versus 37 months (95% CI, 29-63) in those with BM (p=.01). In patients who did not receive ICI therapy, mOS was 31.5 months (95% CI, 23-80) in those without BM versus 17 months (95% CI, 14-NR) in those with BM (p=0.4). Among patients with BM, the mOS from the development of BM was 17.0 months (95% CI, 13-30). Median overall survival was 62 (95% CI: 17-NR months) versus 12 months (95% CI: 5-25 months) from the time of metastatic cancer diagnosis for those who underwent screening versus those who did not (p=0.0001). Conclusions: In our ccRCC population, there is a higher prevalence of brain metastases than previously thought. Overall survival for patients with metastatic ccRCC and brain metastases has improved in the era of ICI therapy. Brain metastases remain associated with poor prognosis and were frequently detected during asymptomatic screening. Patients with brain metastases discovered on screening had improved overall survival compared to those with brain metastases discovered because of symptoms.