Refining the CHAARTED Classification: Clinical Utility of a Novel Integrated Risk Stratification Model Incorporating Gleason Grade and Biochemical Markers in Japanese Patients With Metastatic Hormone‐Sensitive Prostate Cancer

ABSTRACT Objectives In this study, we aimed to develop and validate a novel risk stratification model integrating Gleason grade and biochemical markers to predict the prognosis of Japanese patients with metastatic hormone‐sensitive prostate cancer (mHSPC). We also assessed its clinical utility as a complementary tool to the CHAARTED classification for guiding therapeutic decision‐making. Methods This multicenter retrospective study included patients with mHSPC treated between January 2018 and December 2023 at Yamaguchi University Hospital and its affiliated institutions. Patients who received androgen deprivation therapy combined with either an androgen receptor signaling inhibitor or docetaxel as the initial therapy were included. The primary endpoint was time to castration‐resistant prostate cancer (TTCRPC). Independent prognostic factors were identified using multivariable Cox proportional hazards models, and a new risk classification was constructed. Results In total, 294 patients were analyzed. Multivariable analysis identified Gleason grade group 5, lactate dehydrogenase above the upper limit of normal, and albumin < 4.0 g/dL as independent predictors for TTCRPC. Stratification by the number of these factors (Low, 0–1; Intermediate, 2; High, 3) revealed a clear separation of TTCRPC outcomes (median: not reached, 35 months, and 12 months, respectively; log‐rank p < 0.0001). Combined with CHAARTED volume classification, high‐volume patients with 0–1 risk factors had a prognosis similar to low‐volume patients, whereas those with ≥ 2 factors had significantly poorer outcomes. Conclusions This novel risk model enabled the refinement of prognostic stratification in conjunction with CHAARTED, facilitating tailored treatment intensity among high‐volume patients. Accordingly, further prospective studies are warranted.