Real-world trends in the use and outcomes of novel androgen receptor signaling inhibitor therapy in patients with non-metastatic castration-resistant prostate cancer: A multicenter retrospective study

Background: Although three phase III trials demonstrated significant oncological benefits of novel androgen receptor signaling inhibitors (ARSIs) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC), trends in novel ARSI use have been sparsely documented. Moreover, the safety and oncological benefits of novel ARSIs in real-world nmCRPC settings remain unclear. Methods: This multicenter retrospective study evaluated 318 consecutive patients with nmCRPC treated between 2001 and 2024. Trends in the use of novel ARSIs were analyzed. Adverse events associated with novel ARSIs were assessed using the Common Terminology Criteria for Adverse Events version 5.0. Multivariable Cox proportional hazards regression analyses were conducted to evaluate the effects of novel ARSIs on metastasis-free survival (MFS) and overall survival (OS). Results: The median age and follow-up period after nmCRPC diagnosis were 77 years and 46 months, respectively. Of the 318 patients, 231 (73%) received novel ARSI treatment at some point during nmCRPC management. First-line use of novel ARSIs gradually increased following their initial approval for nmCRPC in 2014. The rate of first-line novel ARSI use was significantly higher in 2020–2024 than in 2014–2019 (68% vs. 33%, P < 0.001). The incidence rates of any-grade and grade ≥3 adverse events associated with novel ARSIs were 23% and 2.2%, respectively. After adjusting for confounding variables, novel ARSIs were independently and significantly associated with prolonged MFS and OS. Conclusions: Novel ARSIs have become a primary treatment strategy for nmCRPC in real-world settings, demonstrating both safety and significant oncological benefits.