title: Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.
abstract: OBJECTIVE
  To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed.
  
  
  METHODS
  Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose <93 Gy (58 patients) and high-dose biologically effective dose >93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure.
  
  
  RESULTS
  The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p <0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p = 0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%.
  
  
  CONCLUSIONS
  Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA. amartinez@beaumont.edu
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Martinez
authors.forename: Gary
authors.initials: G
authors.lastname: Gustafson
authors.forename: José
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Elwood
authors.initials: E
authors.lastname: Armour
authors.forename: Chris
authors.initials: C
authors.lastname: Mitchell
authors.forename: Gregory
authors.initials: G
authors.lastname: Edmundson
authors.forename: William
authors.initials: W
authors.lastname: Spencer
authors.forename: Jannifer
authors.initials: J
authors.lastname: Stromberg
authors.forename: Raywin
authors.initials: R
authors.lastname: Huang
authors.forename: Frank
authors.initials: F
authors.lastname: Vicini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D017430:Prostate-Specific Antigen