Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer

BJU Int. 2017 Nov;120(5B):E80-E86. doi: 10.1111/bju.13856. Epub 2017 Apr 30.


Objectives: To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC).

Materials and methods: We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs).

Results: The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95% CI 5.07-14.7) and PCSM (HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15 months were 9, 19, 40 and 50 months, respectively.

Conclusion: Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials.

Keywords: #ProstateCancer; PSA doubling time; castration-resistant prostate cancer; metastasis; risk stratification.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Disease Progression
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Predictive Value of Tests
  • Prognosis
  • Prostate / pathology
  • Prostate-Specific Antigen / blood*
  • Prostatectomy / mortality
  • Prostatic Neoplasms, Castration-Resistant / blood*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology*
  • Retrospective Studies
  • Time Factors
  • United States / epidemiology
  • Veterans*


  • Biomarkers, Tumor
  • Prostate-Specific Antigen