Evaluating CRPC Definition: Comparing Upfront ARSI and Conventional Hormonal Therapy for Metastatic Hormone Sensitive Prostate Cancer (mHSPC) in Real World Propensity Score Matched Cohort

ABSTRACT Introduction The biology of castration‐resistant prostate cancer (CRPC) status between conventional hormonal therapy and upfront androgen signaling inhibitor (ARSI) treatment might be different, and the biological status of prostate cancer after failure of sequential ARSI in conventional hormonal therapy would be the same as CRPC in upfront ARSI. In this study, we evaluate our proposed definition of CRPC in our cohort with propensity score‐matched analysis. Patients and Methods A total of 885 patients diagnosed with metastatic hormone‐sensitive prostate cancer (mHSPC) who received conventional hormonal therapy, upfront androgen receptor signaling inhibitors (ARSI) with or without docetaxel therapy at Jikei University Hospital and its affiliated institutions, were included in this study. We compared survival outcomes between conventional hormonal therapy and upfront ARSI doublet treatment using conventional CRPC definition or our proposed CRPC definition. Result CRPC‐free survival (CRPCFS) and cancer‐specific survival (CSS) is significantly better in upfront ARSI (upfront (+)) than upfront (–) group (median CRPCFS is 68 months vs. 18 months, median CSS is not reached (NR) and NR, ( p  < 0.0001 and p  = 0.0381), respectively) in propensity score‐matched cohort, although overall survival (OS) is not different. Median CSS and OS after conventional CRPC diagnosis is NR (upfront (–)) and 30 months (upfront (+)) ( p  = 0.0614), and 37 months (upfront (–)) and 24 months (upfront (+)) ( p  = 0.00503). OS is significantly better in upfront (–) than upfront (+) group with conventional CRPC definition. Median CSS and OS after our proposed CRPC diagnosis is 20 months (upfront (–)) and 30 months (upfront (+)) ( p  = 0.389), and 20 months (upfront (–)) and 24 months (upfront (+)) ( p  = 0.932). Conclusion This proposed CRPC definition is thought to reflect the actual biological characteristics of prostate cancer with or without upfront ARSI treatment, and it is thought that the introduction of this definition should be considered when comparing the survival outcome between with or without upfront ARSI treatment.