title: Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer.
abstract: 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).
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA.|Division of Urology, Veterans Affairs Medical Center, Durham, NC, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Howard
authors.affiliation: Department of Urology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Moreira
authors.affiliation: Division of Urology, Veterans Affairs Medical Center, Durham, NC, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: De Hoedt
authors.affiliation: Department of Urology, UCLA School of Medicine, Los Angeles, CA, USA.|Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Aronson
authors.affiliation: Urology Department, University of California San Diego Health System, San Diego, CA, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kane
authors.affiliation: Division of Urology, Department of Surgery, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Amling
authors.affiliation: Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Cooperberg
authors.affiliation: Section of Urology, Veterans Affairs Medical Center, Augusta, GA, USA.|Section of Urology, Medical College of Georgia, Augusta, GA, USA.
authors.forename: Martha K
authors.initials: MK
authors.lastname: Terris
authors.affiliation: Division of Urology, Veterans Affairs Medical Center, Durham, NC, USA.|Division of Urology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000401:mortality / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000401:mortality; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D012189:Retrospective Studies; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D014728:Veterans
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
keywords: #ProstateCancer; PSA doubling time; castration-resistant prostate cancer; metastasis; risk stratification