Abstract
Radiotherapy plus immune checkpoint inhibitors can potentially induce synergistic antitumor immune responses. However, little clinical evidence is established regarding their combination therapy. Here, we aimed to assess whether radiotherapy to the primary tumor impacts on the efficacy of pembrolizumab in advanced urothelial cancer. We retrospectively reviewed 98 advanced urothelial cancer patients receiving pembrolizumab in a second- or later-line setting using our multicenter cohort. Patients were categorized according to a history of radiotherapy to the primary tumor: patients previously exposed to radiotherapy to the primary tumor (Radiotherapy group, 17 patients [17%]) and those not (Nonradiotherapy group, 81 patients [83%]). The associations of radiotherapy to the primary tumor with objective response and survival were evaluated. The Radiotherapy group showed a significantly higher objective response ratio than did the Non-radiotherapy group (65% vs 19%; P < .001). The Radiotherapy group had a higher progression-free survival rate compared with the Nonradiotherapy group (52% vs 28% at 12 months; P = .078), but statistical significance was not reached. The Radiotherapy group had a significantly higher overall survival rate compared with the Non-radiotherapy group (77% vs 50% at 12 months; P = .025). From multivariate analysis, radiotherapy to the primary tumor was an independent predictor for longer overall survival (hazard ratio, 0.31; P = .032) along with Eastern Cooperative Oncology Group performance status ≤1 and the absence of visceral metastasis. Therefore, radiotherapy to the primary tumor may enhance the efficacy of pembrolizumab for patients with advanced urothelial cancer.