title: Biopsy Gleason score and the duration of testosterone suppression among men treated with external beam radiation and 6 months of combined androgen blockade.
abstract: Study Type - Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The return of testosterone to normal levels following short-course androgen blockade in prostate cancer is variable. Factors associated with a longer time to recovery include older age and lower baseline testosterone level. In this study, we found that among men treated with 6 months of combined androgen blockade and radiation therapy, higher biopsy Gleason grade was associated with a shorter time to testosterone normalization.
  
  
  OBJECTIVE
  • To determine whether the biopsy Gleason score is associated with duration of testosterone suppression following 6 months of combined androgen blockade (CAB) and radiation therapy (RT) in men with prostate cancer (PCa).
  
  
  METHODS
  • The study cohort consisted of 221 men with PCa treated with RT and 6 months of CAB between 1996 and 2005. • We defined the duration of testosterone suppression as the time between the last day of CAB and the date the testosterone returned to ≥ 252 ng/dL. We used Cox regression multivariable analysis to relate biopsy Gleason score to duration of testosterone suppression following cessation of CAB.
  
  
  RESULTS
  • A biopsy Gleason score of 8-10 had an adjusted hazard ratio (AHR) of 1.56 (95% confidence interval [CI] 1.04, 2.34; P= 0.03) for a shorter time to testosterone normalization relative to Gleason 6. Specifically, the 51 men with biopsy Gleason score of 8-10 had a median time to testosterone normalization of 17.0 months compared with 22.1 months and 23.8 months for those with biopsy Gleason ≤ 6 and 7, respectively. • Increasing age was significantly associated with a longer duration of testosterone suppression (AHR of 0.95 [95% CI 0.92, 0.97; P < 0.001]) as was a higher baseline PSA (AHR 0.82 [95% CI 0.69, 0.97; P= 0.02]).
  
  
  CONCLUSIONS
  • A biopsy Gleason score of 8-10 was associated with a shorter period of testosterone suppression following 6 months of CAB and RT. These data are consistent with the hypothesis that a factor released from high-grade PCa cells may impact on testosterone production.
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. neil_martin@dfci.harvard.edu
authors.forename: Neil E
authors.initials: NE
authors.lastname: Martin
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chen
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
authors.forename: Clair J
authors.initials: CJ
authors.lastname: Beard
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Loffredo
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
authors.forename: Anthony V
authors.initials: AV
authors.lastname: D'Amico
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009570:Nitriles / Q000627:therapeutic use*; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D013739:Testosterone / Q000037:antagonists & inhibitors*; D014105:Tosyl Compounds / Q000627:therapeutic use*
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D013739:Testosterone; D005485:Flutamide; C053541:bicalutamide