title: Is supplemental external beam radiation therapy necessary for patients with higher risk prostate cancer treated with 103Pd? Results of two prospective randomized trials.
abstract: OBJECTIVE
  To determine the necessity and/or dose of supplemental external beam radiotherapy (EBRT) in conjunction with palladium-103 ((103)Pd) brachytherapy for high-risk prostate cancer patients.
  
  
  METHODS
  Trial 44/20 randomized patients to 44 Gy plus 90 Gy (103)Pd vs. 20 Gy with 115 Gy (103)Pd, and the subsequent trial randomized patients to the 20 Gy arm vs. 125 Gy (103)Pd without EBRT (20/0 trial). Eligibility criteria included clinically organ-confined disease with Gleason scores 7-9 and/or a pretreatment prostate-specific antigen (PSA) 10-20 ng/mL. The brachytherapy prescription dose was prescribed to the prostate gland with generous periprostatic margins. Biochemical failure (BF) was defined as a PSA >0.40 ng/mL after nadir. Median Day 0 minimum dose covering 90% of the prostate volume (D90) was >121.0% of the prescription dose. Multiple parameters were evaluated for effect on outcomes.
  
  
  RESULTS
  In 44/20 trial, 13-year BF, prostate cancer-specific mortality (PCSM), and overall mortality (OM) were 8.2%, 4.0%, and 42.8% vs. 8.0%, 1.0%. and 40.3% for the 44 and 20 Gy arms. In 20/0 trial, 8-year BF, PCSM, and OM were 2.1%, 0%, and 14.4% vs. 3.6%, 0%, and 16.1% in the 20 vs. 0 Gy arms. When stratified by either pretreatment PSA or by Gleason score, supplemental EBRT dose did not impact BF, PCSM, or OM. In multivariate analysis, BF was most closely related to percent positive biopsies and prostate volume. In both trials, patients with biochemically controlled disease had a median PSA of <0.02 ng/mL.
  
  
  CONCLUSIONS
  With high-quality brachytherapy dose distributions, supplemental EBRT did not influence BF or PCSM for patients with intermediate-risk disease. The number of patients with Gleason score 8-9 was too small to determine the role of supplemental EBRT in that cohort.
authors.affiliation: Schiffler Cancer Center, Department of Radiation Oncology, Wheeling Jesuit University, Wheeling, WV; Department of Urology, Wheeling Hospital, Wheeling, WV. Electronic address: gmerrick@urologicresearchinstitute.org.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Merrick
authors.affiliation: Puget Sound Health Care System, Department of Radiation Oncology, Seattle, WA.
authors.forename: Kent E
authors.initials: KE
authors.lastname: Wallner
authors.affiliation: Schiffler Cancer Center, Department of Radiation Oncology, Wheeling Jesuit University, Wheeling, WV; Ohio University Eastern, St. Clairsville, OH.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Galbreath
authors.affiliation: Schiffler Cancer Center, Department of Radiation Oncology, Wheeling Jesuit University, Wheeling, WV.
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Butler
authors.affiliation: Schiffler Cancer Center, Department of Radiation Oncology, Wheeling Jesuit University, Wheeling, WV.
authors.forename: Ryan
authors.initials: R
authors.lastname: Fiano
authors.affiliation: Department of Radiation Oncology, Dana-Farber/Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Orio
authors.affiliation: Department of Pathology, Wheeling Hospital, Wheeling, WV.
authors.forename: Edward
authors.initials: E
authors.lastname: Adamovich
mesh_terms: D000368:Aged; D001706:Biopsy; D001918:Brachytherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010165:Palladium / Q000627:therapeutic use*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D011868:Radioisotopes / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D012307:Risk Factors; D015996:Survival Rate; D017211:Treatment Failure
chemical_list: D011868:Radioisotopes; D010165:Palladium; D017430:Prostate-Specific Antigen
keywords: Brachytherapy; Higher risk; Prospective randomized trial; Supplemental external beam radiation therapy