The Effect of Upfront Intensive Therapy on Primary Resistance in Metastatic Castration-sensitive Prostate Cancer: A Multicenter Retrospective Study

Abstract We investigated the effect of upfront intensive therapy on primary resistance in patients with metastatic castration-sensitive prostate cancer (mCSPC) in real-world practice. We retrospectively evaluated the medical records of 348 patients with newly diagnosed mCSPC who had a high tumor-burden between January 2008 and May 2021. We compared the oncological outcomes between patients who received conventional androgen deprivation therapy ± bicalutamide (ADT group) and those treated with upfront intensive therapies (upfront group). The primary purpose was comparing the rate of primary resistance between the ADT and upfront groups. The primary resistance was defined as a castration-resistant prostate cancer (CRPC) progression < 6 or < 12 months. The secondary purposes were comparing the CRPC-free survival and overall survival (OS) between the ADT and upfront groups, and assessing safety in the upfront group. We identified 206 and 142 patients for the ADT and upfront groups, respectively. We found the rate of CRPC progression < 6 and < 12 months was significantly lower in the upfront group (9.2% and 18%, respectively) than that in the ADT group (21% and 51%, respectively). The upfront therapy was significantly associated with favorable CRPC-free survival and OS than that in the ADT group in propensity-score adjusted models. A higher rate of any grade adverse events was observed in the upfront docetaxel (94%) than that of the upfront abiraterone (34%) or apalutamide/enzalutamide (39%). In conclusion, the upfront intensive therapy significantly improved the rate of primary resistance and oncological outcomes in patients with mCSPC in real-world practice.