Faculty Collaboration Database

Cardiovascular Mortality Following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08. Eur Urol 2016 Feb;69(2):204-10

Date

09/13/2015

Pubmed ID

26362090

Pubmed Central ID

PMC4784682

DOI

10.1016/j.eururo.2015.08.027

Scopus ID

2-s2.0-84952870503 (requires institutional sign-in at Scopus site)   36 Citations

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.

DESIGN, SETTING, AND PARTICIPANTS: 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.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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.

RESULTS AND LIMITATIONS: 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.

PATIENT SUMMARY: 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.

Author List

Voog JC, Paulus R, Shipley WU, Smith MR, McGowan DG, Jones CU, Bahary JP, Zeitzer KL, Souhami L, Leibenhaut MH, Rotman M, Husain SM, Gore E, Raben A, Chafe S, Sandler HM, Efstathiou JA

Author

Elizabeth M. Gore MD Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Antineoplastic Agents, Hormonal
Cardiovascular Diseases
Flutamide
Follow-Up Studies
Goserelin
Humans
Incidence
Leuprolide
Male
Middle Aged
Proportional Hazards Models
Prostatic Neoplasms
Retrospective Studies
Survival Rate
Time Factors