title: Survival and PSA-markers for mortality and metastasis in nonmetastatic prostate cancer treated with androgen deprivation therapy.
abstract: Few studies have examined the risk of developing castration-resistant prostate cancer (CRPC), metastasis, and mortality among nonmetastatic prostate cancer (M0-PC) patients treated with androgen deprivation therapy (ADT). We estimated the incidence of these outcomes among M0-PC patients on ADT and identified prostate-specific antigen (PSA) based biomarkers for mortality and metastasis.
  
  
  
  This population-based cohort study included all nonmetastatic prostate cancer patients in Northern and Central Denmark Regions during 1997-2010, identified through registry data. Primary outcomes were metastasis, overall survival, and bone metastasis-free survival (BMFS). We estimated relative risks (RR) associated with PSA and PSA doubling-time (PSA-DT), measured as time-varying variables beginning at ADT treatment start.
  
  
  
  We included 2494 M0-PC patients treated with ADT, of whom 1617 (80%) developed CRPC during follow-up. One-fourth of the patients developed metastases within 5 years; bone metastases (BM) accounted for 81% of all metastases. Median survival time was 4.4 years. Compared with PSA <8 ng/mL, PSA ≥8 ng/mL was associated with an adjusted RR of 14.0 (95% confidence interval [CI]: 10.2, 19.0) for BM, 4.4 (CI: 3.9, 5.0) for all-cause mortality, and RR of 4.8 (CI: 4.3, 5.4) for the inverse of BMFS. PSA-DT ≤6 months was associated with an adjusted RR of 7.6 (95% CI: 6.1, 9.5) for BM, RR of 5.9 (CI: 5.2, 6.6) for all-cause mortality, and RR 6.6 (CI: 5.9, 7.4) for the inverse of BMFS.
  
  
  
  PSA ≥8 ng/mL and PSA-DT ≤6 months are strong predictors of mortality and bone metastasis. The poor prognosis observed in this study may reflect inclusion of patients with severe prostate cancer by requiring repeated PSA measurements.
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Electronic address: maryniel@rm.dk.
authors.forename: Mary
authors.initials: M
authors.lastname: Nguyen-Nielsen
authors.affiliation: Center for Observational Research, Amgen, Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. Electronic address: aliede@amgen.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Liede
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Electronic address: mlm@econ.au.dk.
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Maegbaek
authors.affiliation: Department of Urology, Aarhus University Hospital, Brendstrupgårdsvej 100, 8200 Aarhus N, Denmark. Electronic address: borre@clin.au.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Borre
authors.affiliation: Department of Urology, Aalborg University Hospital, Reberbansgade 15, 9100 Aalborg, Denmark. Electronic address: niha@rn.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Harving
authors.affiliation: Center for Observational Research, Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA. Electronic address: rohinih@amgen.com.
authors.forename: Rohini Khorana
authors.initials: RK
authors.lastname: Hernandez
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Electronic address: hts@clin.au.dk.
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, Denmark. Electronic address: ve@clin.au.dk.
authors.forename: Vera
authors.initials: V
authors.lastname: Ehrenstein
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality*
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen
keywords: Androgen deprivation therapy; Bone metastases; Prostatic neoplasms; Survival