title: Cardiovascular Mortality Following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08.
abstract: BACKGROUND
  Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease.
  
  
  OBJECTIVE
  We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase III trial.
  
  
  METHODS
  A total of 1979 men with clinically localized (T1b-2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin-releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors.
  
  
  METHODS
  The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed disease-specific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA.
  
  
  CONCLUSIONS
  Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard ratio: 1.07; confidence interval, 0.81-1.42; p=0.62). Increased CVM was not observed in patients at low risk of PCa death or at high risk of cardiac-related death.
  
  
  CONCLUSIONS
  Data from patients enrolled in RTOG 94-08 support the hypothesis that ADT does not increase CVM risk in men with clinically localized PCa treated with short-course GnRH agonist therapy. These data support ADT use in settings with proven survival benefit.
  
  
  RESULTS
  We investigated the controversial relationship between hormone therapy and cardiovascular mortality in men with prostate cancer (PCa) treated with radiation in a large randomized trial. Our data suggest that hormone therapy does not increase the risk of cardiovascular death in patients with clinically localized PCa and support the use of such therapy in settings with proven survival benefit.
authors.affiliation: Harvard Radiation Oncology Program, Boston, MA, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Voog
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Paulus
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.affiliation: Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: McGowan
authors.affiliation: Sutter Cancer Centers (Radiological Associates of Sacramento), Sacramento, CA, USA.
authors.forename: Christopher U
authors.initials: CU
authors.lastname: Jones
authors.affiliation: CHUM-Hospital Norte-Dame, Montreal, Quebec, Canada.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bahary
authors.affiliation: Department of Radiation Oncology, Albert Einstein Medical Center, Philadelphia, PA, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Zeitzer
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.affiliation: Sutter Cancer Centers (Radiological Associates of Sacramento), Sacramento, CA, USA.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Leibenhaut
authors.affiliation: Brooklyn MB-CCOP/SUNY Downstate, Brooklyn, NY, USA.
authors.forename: Marvin
authors.initials: M
authors.lastname: Rotman
authors.affiliation: Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Husain
authors.affiliation: Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gore
authors.affiliation: Christiana Care Health Services, Inc. CCOP, Newark, DE, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Raben
authors.affiliation: Cross Cancer Institute, Edmonton, Alberta, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Chafe
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jefstathiou@partners.org.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Efstathiou
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000401:mortality*; D005485:Flutamide / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D017273:Goserelin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D016729:Leuprolide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D005485:Flutamide; D016729:Leuprolide
keywords: Androgen deprivation therapy; Cardiovascular mortality; Hormone therapy; Prostate cancer; Radiation therapy; Survival