Impact of Immunohistochemical PSA and Ki‐67 Expression on Prognosis in Metastatic Castration‐Sensitive Prostate Cancer

Background and Objective Treatment selection for metastatic castration‐sensitive prostate cancer (mCSPC) remains challenging, as reliable and practical biomarkers predicting response to androgen receptor pathway inhibitor (ARPI)‐based therapy are limited. We evaluated whether prostate‐specific antigen (PSA) and Ki‐67 expression in diagnostic biopsy specimens can predict oncologic outcomes in patients with mCSPC treated with ARPI–androgen deprivation therapy (ADT) doublet therapy, and whether these biomarkers can guide optimal treatment selection. Methods This retrospective multicenter study included 58 patients with mCSPC who received ARPI–ADT doublet therapy between 2018 and 2024. Immunohistochemical staining for PSA and Ki‐67 was performed on diagnostic biopsy specimens. Receiver operating characteristic curve analyses were used to determine optimal cutoff values for predicting progression to castration‐resistant prostate cancer (CRPC). Survival outcomes were analyzed using the Kaplan–Meier method and Cox proportional hazards models. Exploratory analyses included patients treated with triplet therapy (ADT + docetaxel + darolutamide) or upfront docetaxel. Results Low PSA expression, high Ki‐67 expression, and a bone metastasis extent of disease (EOD) score ≥ 3 were independently associated with shorter CRPC‐free survival (CRPC‐FS). Stratification by risk factors (0, 1, or 2) showed a stepwise decline in CRPC‐FS. In exploratory analyses, triplet therapy achieved the longest CRPC‐FS and progression‐free survival 2 among high‐risk patients, whereas no significant differences among treatment modalities were observed in the low‐risk group. Conclusion Immunohistochemical PSA and Ki‐67 expression provide practical prognostic information for patients with metastatic castration‐sensitive prostate cancer. Combined assessment with EOD ≥ 3 identifies a high‐risk subgroup with unfavorable clinical outcomes.