title: The interval to biochemical failure is prognostic for metastasis, prostate cancer-specific mortality, and overall mortality after salvage radiation therapy for prostate cancer.
abstract: OBJECTIVE
  To investigate the utility of the interval to biochemical failure (IBF) after salvage radiation therapy (SRT) after radical prostatectomy (RP) for prostate cancer as a surrogate endpoint for distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM).
  
  
  METHODS
  A retrospective analysis of 575 patients treated with SRT after RP from a single institution. Of those, 250 patients experienced biochemical failure (BF), with the IBF defined as the time from commencement of SRT to BF. The IBF was evaluated by Kaplan-Meier and Cox proportional hazards models for its association with DM, PCSM, and OM.
  
  
  RESULTS
  The median follow-up time was 85 (interquartile range [IQR] 49.8-121.1) months, with a median IBF of 16.8 (IQR, 8.5-37.1) months. With a cutoff time of 18 months, as previously used, 129 (52%) of patients had IBF ≤18 months. There were no differences among any clinical or pathologic features between those with IBF ≤ and those with IBF >18 months. On log-rank analysis, IBF ≤18 months was prognostic for increased DM (P<.0001, HR 4.9, 95% CI 3.2-7.4), PCSM (P<.0001, HR 4.1, 95% CI 2.4-7.1), and OM (P<.0001, HR 2.7, 95% CI 1.7-4.1). Cox proportional hazards models with adjustment for other clinical variables demonstrated that IBF was independently prognostic for DM (P<.001, HR 4.9), PCSM (P<.0001, HR 4.0), and OM (P<.0001, HR 2.7). IBF showed minimal change in performance regardless of androgen deprivation therapy (ADT) use.
  
  
  CONCLUSIONS
  After SRT, a short IBF can be used for early identification of patients who are most likely to experience progression to DM, PCSM, and OM. IBF ≤18 months may be useful in clinical practice or as an endpoint for clinical trials.
authors.affiliation: Department of Radiation Oncology, The University of Michigan Medical Center, Ann Arbor, MI 48109, USA. Skylerjohn3101@gmail.com
authors.forename: Skyler
authors.initials: S
authors.lastname: Johnson
authors.forename: William
authors.initials: W
authors.lastname: Jackson
authors.forename: Darren
authors.initials: D
authors.lastname: Li
authors.forename: Yeohan
authors.initials: Y
authors.lastname: Song
authors.forename: Corey
authors.initials: C
authors.lastname: Foster
authors.forename: Ben
authors.initials: B
authors.lastname: Foster
authors.forename: Jessica
authors.initials: J
authors.lastname: Zhou
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Vainshtein
authors.forename: Felix
authors.initials: F
authors.lastname: Feng
authors.forename: Daniel
authors.initials: D
authors.lastname: Hamstra
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use; D002423:Cause of Death; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000401:mortality*; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen