title: Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy-A Multi-Institutional Observational Study.
abstract: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer.
  
  
  
  Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus.
  
  
  
  With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis.
  
  
  
  The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address: pisansky.thomas@mayo.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Pisansky
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Shree
authors.initials: S
authors.lastname: Agrawal
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, Duke Cancer Institute, Durham, North Carolina.
authors.forename: Bridget F
authors.initials: BF
authors.lastname: Koontz
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Liauw
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Efstathiou
authors.affiliation: Department of Radiation Oncology, Washington University, St. Louis, Missouri.
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Michalski
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: Department of Radiation Oncology, University of Miami, Miami, Florida.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Abramowitz
authors.affiliation: Department of Radiation Oncology, University of Miami, Miami, Florida.
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Anscher
authors.affiliation: Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia; Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, Virginia.
authors.forename: Drew
authors.initials: D
authors.lastname: Moghanaki
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Den
authors.affiliation: Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Stephans
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Zietman
authors.affiliation: Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina.
authors.forename: W Robert
authors.initials: WR
authors.lastname: Lee
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kattan
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stephenson
authors.affiliation: Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Rahul D
authors.initials: RD
authors.lastname: Tendulkar
mesh_terms: D000368:Aged; D016009:Chi-Square Distribution; D016208:Databases, Factual / Q000706:statistics & numerical data; D004307:Dose-Response Relationship, Radiation; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000532:radiotherapy* / Q000601:surgery; D016879:Salvage Therapy / Q000379:methods*; D018401:Sample Size; D012669:Seminal Vesicles / Q000473:pathology; D013997:Time Factors; D017211:Treatment Failure; D014481:United States
chemical_list: D017430:Prostate-Specific Antigen