Percentage of free to total PSA as a biomarker of survival in metastatic castration-resistant prostate cancer

Silagy, AW; Herrera-Caceres, JO; Woon, DTS; Kostos, L; Bernardino, R; Yiu, TW; Wettstein, MS; Goldberg, H; Shiakh, H; Nason, G; Zlotta, A; Diamantis, E; Bolton, D; Fleshner, N

Author(s): Silagy, AW; Herrera-Caceres, JO; Woon, DTS; Kostos, L; Bernardino, R; Yiu, TW; Wettstein, MS; Goldberg, H; Shiakh, H; Nason, G; Zlotta, A; Diamantis, E; Bolton, D; Fleshner, N;
Details: Publication Year 2025-08,Volume 136,Issue #2,Page 329-335
Journal Title: BJU International
Publication Type: Research article
Abstract: OBJECTIVE: To analyse whether the percentage of free to total prostate-specific antigen (%fPSA) is a prognostic biomarker in metastatic castration-resistant prostate cancer (mCRPC), as novel studies suggest an elevated %fPSA is associated with adverse oncological outcomes for men with biochemical recurrence of prostate cancer. PATIENTS AND METHODS: A biobank prospectively collated at mCRPC diagnosis was analysed for %fPSA. Clinicopathological characteristics, systemic therapies and survival outcomes were recorded. Patients were stratified by a %fPSA cut-off of 15%. Cox proportional hazard models evaluated whether %fPSA was associated with overall survival (OS) and cancer-specific survival (CSS) across the cohort and by treatment. RESULTS: A total of 254 patients analysed with newly diagnosed mCRPC: 161 (63%) men having a %fPSA ≥15%. The median follow-up was 25.6 months. The median cohort OS and CSS was 39.6 and 43.8 months, respectively. Patients with a %fPSA ≥15% had lower median PSA level (31.30 vs 50.80 ng/mL; P = 0.007) and otherwise comparable clinicopathological and treatment profiles to men with a %fPSA <15%. Adjusting for PSA and on multivariable analysis, a %fPSA ≥15% was associated with shorter OS (multivariable hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.02-2.40; P = 0.039). Among men treated with docetaxel, a %fPSA ≥15% was associated with worse OS (HR 1.84, 95% CI 1.03-3.26; P = 0.038) and CSS. Conversely, %fPSA was not associated with outcomes for men receiving androgen receptor pathway inhibitors (abiraterone acetate or enzalutamide). CONCLUSION: An elevated %fPSA appears to be an adverse prognostic biomarker. Findings are consistent with biochemical recurrence studies, suggesting a biological basis. Validation and mechanistic studies are warranted.
Keywords: Humans; Male; *Prostatic Neoplasms, Castration-Resistant/mortality/blood/pathology/drug therapy; *Prostate-Specific Antigen/blood; Aged; Middle Aged; Prognosis; *Biomarkers, Tumor/blood; Prospective Studies; Aged, 80 and over; Neoplasm Metastasis; Psa; biomarker; metastases; oncology; prostate cancer; survival
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1111/bju.16751
Open Access at Publisher's Site: https://doi.org/10.1111/bju.16751
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-07-08 04:31:27

Last Modified: 2025-08-08 07:40:21