title: Less advanced disease at initiation of salvage androgen deprivation therapy is associated with decreased mortality following biochemical failure post-salvage radiation therapy.
abstract: BACKGROUND
  The optimal clinical context for initiation of salvage androgen deprivation therapy (SADT) following the biochemical recurrence of localized prostate cancer remains controversial. We chose to investigate if disease burden at time of SADT initiation is associated with clinical outcomes following biochemical failure (BF) post-salvage radiation therapy (SRT).
  
  
  METHODS
  Medical records of 575 patients receiving SRT at a single institution from 1986-2010 were retrospectively reviewed. Of 250 patients experiencing BF post-SRT, 172 had a calculable prostate-specific antigen doubling time (PSADT) prior to SADT initiation. These patients comprise the analyzed cohort and were divided into four groups based on characteristics at SADT initiation: those with PSADTs >3 months without distant metastasis (DM) (group 1 [less advanced disease], n=62), those with PSADTs <3 months without DM (group 2 [more advanced disease], n=28), those with DM (group 3 [more advanced disease], n=32), and those not receiving SADT during follow-up (group 4, n=50). Endpoints included prostate cancer-specific mortality (PCSM) and overall mortality (OM). Kaplan-Meier methods were used to estimate survival, and Cox proportional hazards models were used for multivariate analysis.
  
  
  RESULTS
  Median follow-up post-SRT was 7.9 years. Patients starting SADT with more advanced disease were at significantly increased risk for PCSM (hazard ratio [HR]:2.8, 95% confidence interval [CI]: 1.4-5.6, p=0.005) and OM (HR:1.9, 95% CI: 1.0-3.5, p=0.04) compared to those receiving SADT with less advanced disease. PCSM and OM did not significantly differ between groups 1 and 4 or groups 2 and 3. Of note, patients in group 4 had very long PSADTs (median = 27.0 months) that were significantly longer than those of group 1 (median = 6.0 months) (p<0.001). Multivariate analysis including groups 1-3 found a pre-SADT PSADT <3 months to be the most significant predictor of PCSM (HR:4.2, 95% CI: 1.6-11.1, p=0.004) and the only significant predictor of OM (HR:2.9, 95% CI: 1.3-6.7, p=0.01).
  
  
  CONCLUSIONS
  Less advanced disease at initiation of SADT is associated with decreased PCSM and OM following BF post-SRT; however, observation may be reasonable for patients with very long PSADTs. A PSADT <3 months prior to SADT initiation significantly predicts an increased risk of PCSM and OM in this patient demographic.
authors.affiliation: Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Dr, Ann Arbor, MI, 48105, USA. ccfoster@med.umich.edu.
authors.forename: Corey C
authors.initials: CC
authors.lastname: Foster
authors.affiliation: Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Dr, Ann Arbor, MI, 48105, USA. wcj@med.umich.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: Jackson
authors.affiliation: Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Dr, Ann Arbor, MI, 48105, USA. fosterbc@med.umich.edu.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Foster
authors.affiliation: Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Dr, Ann Arbor, MI, 48105, USA. skylerj@med.umich.edu.
authors.forename: Skyler B
authors.initials: SB
authors.lastname: Johnson
authors.affiliation: Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Dr, Ann Arbor, MI, 48105, USA. ffeng@med.umich.edu.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Dr, Ann Arbor, MI, 48105, USA. dhamm@med.umich.edu.|The University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI, 48105, USA. dhamm@med.umich.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy; D011878:Radiotherapy / Q000009:adverse effects*; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000401:mortality*; D015996:Survival Rate
chemical_list: D000726:Androgen Antagonists