High-dose adjuvant radiotherapy after radical prostatectomy with or without androgen deprivation therapy

Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):960-5. doi: 10.1016/j.ijrobp.2011.09.007. Epub 2011 Dec 13.

Abstract

Purpose: 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 and materials: 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.

MeSH terms

  • Aged
  • Analysis of Variance
  • Androgen Antagonists / therapeutic use*
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / radiation effects
  • Humans
  • Lymph Node Excision / methods
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prostate-Specific Antigen / blood
  • Prostatectomy / methods*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Prostatic Neoplasms / surgery*
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant / adverse effects
  • Radiotherapy, Adjuvant / methods
  • Radiotherapy, Conformal / adverse effects
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Retrospective Studies
  • Seminal Vesicles / pathology
  • Seminal Vesicles / radiation effects
  • Urogenital System / drug effects
  • Urogenital System / radiation effects

Substances

  • Androgen Antagonists
  • Prostate-Specific Antigen