The utility of the [−2]pro‐prostate‐specific antigen level as a prognostic marker in patients with castration‐resistant prostate cancer treated with enzalutamide

BACKGROUND The prostate health index (phi) derived using [-2]pro-prostate-specific antigen (p2PSA), a precursor of PSA, has been shown to predict cancer in the gray zone. However, the utility of p2PSA in predicting outcomes for castration-resistant prostate cancer (CRPC) patients remains unknown. Therefore, in this study, we aimed to evaluate the usefulness of p2PSA in predicting the efficacy and prognosis of enzalutamide treatment in CRPC patients. METHODS We conducted a prospective study of CRPC patients treated with enzalutamide at our institution, measuring p2PSA levels in 98 pre-treatment serum samples. All patients were divided into two groups based on the median values of each parameter. The PSA progression-free survival (PSA-PFS) and overall survival (OS) were compared using the Kaplan-Meier method. This study was approved by the Institutional Review Board of Gunma University Hospital (IRB No. 2021-092, 1983). RESULTS The median PSA level before enzalutamide treatment was 25.59 ng/mL, the median p2PSA level was 208.75 pg/mL, and the median phi was 187.95. PSA, p2PSA, and phi were not all predictors of PSA-PFS. However, the OS was significantly better in the low-value groups (log-rank p-values of PSA, p2PSA, and phi were 0.024, 0.034, and 0.018, respectively). In the docetaxel (DOC)-naive group (n = 58), PSA was not a predictor of OS, but p2PSA and phi were significantly associated with better OS in the low group. This relationship was not observed in the DOC-treated group. CONCLUSIONS Our study elucidates the usefulness of p2PSA in predicting outcomes for CRPC patients treated with enzalutamide. It suggests that p2PSA and phi may be prognostic markers after enzalutamide administration in CRPC patients.