title: Combining prostate-specific antigen nadir and time to nadir allows for early identification of patients at highest risk for development of metastasis and death following salvage radiation therapy.
abstract: OBJECTIVE
  Little is known regarding the prognostic capability of prostate-specific antigen (PSA) nadir (nPSA) and time to nPSA (TnPSA) following salvage radiation therapy (SRT) for biochemical failure (BF) postradical prostatectomy (RP). We sought to assess their prognostic significance in this setting.
  
  
  METHODS
  A total of 448 patients who received SRT without androgen deprivation therapy at a single academic institution were included in this retrospective analysis. Univariate analysis and multivariate Cox proportional hazards models were used to assess BF, distant metastasis (DM), prostate cancer-specific death (PCSD), and overall survival (OS). A prognostic nomogram incorporating nPSA and TnPSA was developed and validated in randomly allocated training and validation cohorts.
  
  
  RESULTS
  Median follow-up post-SRT was 64 months. Median nPSA and TnPSA were undetectable and 6.7 months, respectively. On univariate analysis, a detectable nPSA (P < .01) and TnPSA <6 months (P < .01) were predictive of all outcomes. In a training cohort, a 14-point nomogram incorporating detectable nPSA, TnPSA, Gleason score, pre-radiation therapy PSA, and seminal vesicle invasion predicted BF (hazard ratio[HR], 1.4; P < .0001), DM (HR, 1.3; P < .0001), PCSD (HR, 1.3; P < .0001), and decreased OS (HR, 1.2; P < .0001). Adding nPSA and TnPSA improved the prognostic value of the nomogram compared to using clinical predictors only. The nomogram was evaluated in a validation cohort where it was predictive of BF (c-index = 0.77), DM (0.73), and PCSD (0.69).
  
  
  CONCLUSIONS
  Patients with a detectable nPSA also having a TnPSA <6 months post-SRT are at high-risk for DM, PCSD, and decreased OS. These patients are unlikely to have clinically localized disease and should be considered for initiation of systemic therapies.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: William C
authors.initials: WC
authors.lastname: Jackson
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Skyler B
authors.initials: SB
authors.lastname: Johnson
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Foster
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Corey
authors.initials: C
authors.lastname: Foster
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Darren
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Yeohan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Vainshtein
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jessica
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan. Electronic address: ffeng@med.umich.edu.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis
chemical_list: D017430:Prostate-Specific Antigen