Development and Validation of the JIKEI-YAYOI Score for Predicting Castration Resistance in Metastatic Castration-Sensitive Prostate Cancer Treated With ARSI-Based Doublet Therapy.

BACKGROUND

Metastatic castration-sensitive prostate cancer (mCSPC) is a heterogeneous disease with variable clinical outcomes despite advances in androgen receptor signaling inhibitor (ARSI)-based therapy. We aimed to develop and externally validate a prognostic model for predicting progression to castration-resistant prostate cancer (CRPC) in patients with mCSPC.

METHODS

This multicenter retrospective study included patients with mCSPC treated with ARSI doublet therapy. The development cohort comprised 388 patients, whereas the external validation cohort included 451 patients. Prognostic factors for CRPC-free survival (CRPC-FS) were identified using Cox proportional hazards regression models. A point-based risk score (JIKEI-YAYOI score) was derived from regression coefficients. Model performance was evaluated through assessment of discrimination, calibration, and external validation.

RESULTS

In the development cohort, the median CRPC-FS was 21 months. Grade Group, extent of disease score, hemoglobin, and lactate dehydrogenase were independently associated with CRPC progression and were incorporated into the model. The model demonstrated good discrimination (apparent C-index, 0.715; optimism-corrected C-index, 0.720). The JIKEI-YAYOI score ranged from 0 to 8, corresponding to a 3-year CRPC risk of 10.6%-93.2%. Patients were stratified into low-risk (≤ 2), intermediate-risk (3-4), and high-risk (≥ 5) groups, with significantly different CRPC-FS and overall survival (both p < 0.001). External validation confirmed good discrimination, calibration, and risk stratification.

CONCLUSIONS

The JIKEI-YAYOI score is a simple, clinically applicable tool for predicting progression to CRPC in patients with mCSPC. Using routinely available clinical variables, it enables individualized risk assessment and may support clinical decision-making regarding surveillance and treatment strategies.