title: Hypofractionated conformal HDR brachytherapy in hormone naïve men with localized prostate cancer. Is escalation to very high biologically equivalent dose beneficial in all prognostic risk groups?
abstract: OBJECTIVE
  To analyze the long-term effect of local dose escalation using conformal hypofractionated high-dose-rate brachytherapy (HDR-BT) boost and pelvic external-beam radiation therapy (EBRT) in hormone-naïve men with localized prostate cancer.
  
  
  METHODS
  A total of 579 men were consecutively treated with pelvic EBRT and dose escalating HDR-BT since 1986 in two prospective trials: 378 patients at William Beaumont Hospital (1991-2002), and 201 patients at Kiel University (1986-1999). BT optimization was done modulating both, the dwell times and spatial source positions. A short course of neoadjuvant/concurrent androgen deprivation therapy was given to 222 patients. Hormone-naïve patients only (n = 324) with a follow-up > or = 18 months were analyzed. All patients had at least one poor prognostic factor (stage > or = T2b, Gleason Score > or = 7, pretreatment prostate-specific antigen [PSA] > or = 10 ng/ml): any one factor 122 patients, any two factors 122 patients, and three factors 80 patients. This cohort was stratified by equivalent dose (ED): dose level 1, < or = 94 Gy, n = 58, and dose level 2, > 94 Gy, n = 266, assuming an alpha/beta ratio of 1.2. The ASTRO definition for biochemical failure was used.
  
  
  RESULTS
  Mean follow-up was 5.3 years (1.5-13.9 years). For all 324 patients, the 5-year biochemical control (BC) rate was 79%. Cancer-specific survival was 98%, and overall survival 90%. Similar analysis by institution demonstrated no difference in outcomes. For the entire cohort of hormone-naïve men, dose escalation to > 94 Gy resulted in a better 5-year BC of 59% versus 85% (p < 0.001). Discriminating by risk group a striking dose escalation effect was seen in the groups with two or three poor prognostic factors (p = 0.022 and < 0.001, respectively). In the group with only one poor prognostic factor, no statistical difference could be detected questioning the need for ED > 94 Gy.
  
  
  CONCLUSIONS
  The results demonstrate that conformal HDR-BT is a successful method for delivering very high radiation dose to the prostate. The ability to escalate dose to ED > 94 Gy was reflected in improved long-term outcomes in terms of BC, significantly for those patients with two or three poor prognostic factors reaching BC rates of 85%.
authors.affiliation: Clinic for Radiation Therapy, University Hospital Schleswig Holstein, Campus Kiel, Germany. galalae@onco.uni-kiel.de
authors.forename: Razvan M
authors.initials: RM
authors.lastname: Galalae
authors.forename: Alvaro
authors.initials: A
authors.lastname: Martinez
authors.forename: Nils
authors.initials: N
authors.lastname: Nuernberg
authors.forename: Gregory
authors.initials: G
authors.lastname: Edmundson
authors.forename: Gary
authors.initials: G
authors.lastname: Gustafson
authors.forename: Jose
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kimming
mesh_terms: D000206:Actuarial Analysis; D001918:Brachytherapy / Q000379:methods*; D006801:Humans; D008297:Male; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D017430:Prostate-Specific Antigen