title: High-dose adjuvant radiotherapy after radical prostatectomy with or without androgen deprivation therapy.
abstract: OBJECTIVE
  To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT).
  
  
  METHODS
  Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification.
  
  
  RESULTS
  After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT.
  
  
  CONCLUSIONS
  This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.
authors.affiliation: Department of Radiotherapy, Ghent University Hospital, Ghent, Belgium. piet.ost@ugent.be
authors.forename: Piet
authors.initials: P
authors.lastname: Ost
authors.forename: Cesare
authors.initials: C
authors.lastname: Cozzarini
authors.forename: Gert
authors.initials: G
authors.lastname: De Meerleer
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiorino
authors.forename: Bruno
authors.initials: B
authors.lastname: De Potter
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.forename: Evi V T
authors.initials: EV
authors.lastname: Nagler
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Valérie
authors.initials: V
authors.lastname: Fonteyne
authors.forename: Nadia
authors.initials: N
authors.lastname: Di Muzio
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008197:Lymph Node Excision / Q000379:methods; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects; D012189:Retrospective Studies; D012669:Seminal Vesicles / Q000473:pathology / Q000528:radiation effects; D014566:Urogenital System / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen