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

Lauren E. Howard, Daniel Moreira, Amanda De Hoedt, William J. Aronson, Christopher J. Kane, Christopher Amling, Matthew R. Cooperberg, Martha K. Terris, Stephen J. Freedland

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Abstract

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.

Original languageEnglish (US)
JournalBJU International
DOIs
StateAccepted/In press - 2017

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Keywords

  • #ProstateCancer
  • Castration-resistant prostate cancer
  • Metastasis
  • PSA doubling time
  • Risk stratification

ASJC Scopus subject areas

  • Urology

Cite this

Howard, L. E., Moreira, D., De Hoedt, A., Aronson, W. J., Kane, C. J., Amling, C., Cooperberg, M. R., Terris, M. K., & Freedland, S. J. (Accepted/In press). Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU International. https://doi.org/10.1111/bju.13856