Concurrent palliative radiation with pembrolizumab for platinum-refractory urothelial carcinoma is associated with improved overall survival

Background and Purpose: Pembrolizumab has now become a standard of care in metastatic urothelial carcinoma (mUC), although the treatment effect of the drug substantially differs among individuals. Emerging evidence suggests that radiotherapy exerts a synergistic effect with PD-1 blockade. We sought to elucidate the survival outcomes in patients who underwent palliative radiation with the pembrolizumab treatment. Methods: We retrospectively investigated our multi-institutional dataset of 235 platinum-refractory mUC patients treated with pembrolizumab as second-line treatment, collected from January 2018 and October 2021. Propensity score matching was performed to reduce biases by potential confounding factors for overall survival (OS). Results: With a median follow-up of 6.8 months, the median OS from the initiation of pembrolizumab was 13 months in 235 patients. Palliative radiation was performed in 71 (30.2%) patients for whom the median radiation dose and fraction were 30 Gy and 10 fractions, respectively. Irradiated sites were bone in 24 (33.8%), lymph node in 17 (23.9%), lung in 3 (4.2%), brain in 8 (11.3%), and other sites in 19 (26.8%). OS from the initiation of pembrolizumab was significantly longer in patients who underwent concurrent palliative radiation with pembrolizumab (39 patients: median OS: 21 months) than in both patients with palliative radiation before pembrolizumab (32 patients: median OS: 9 months) (p = 0.001) and those without palliative radiation throughout the follow-up (164 patients: median OS: 13 months) (p = 0.019). After the propensity-score matching by putative confounding factors, longer OS in patients treated with concurrent palliative radiation with pembrolizumab (n = 36) was still observed compared to patients without the concurrent palliative radiation (n = 36) in the pair matched cohort (median OS of 29 and 13 months, respectively, p = 0.033). Conclusions: Our findings suggest that the concurrent administration of palliative radiation with pembrolizumab offers a favorable effect on OS in platinum-refractory mUC patients.