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.