Cardiovascular mortality and duration of androgen deprivation for locally advanced prostate cancer: analysis of RTOG 92-02.
OBJECTIVE
Gonadotropin-releasing hormone agonists (GnRHa) are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about their potential effects on cardiovascular mortality. We assessed the relationship between duration of GnRHa therapy and cardiovascular mortality in a large randomized trial of men treated with short-term versus longer-term adjuvant goserelin and radiation therapy (RT) for locally advanced prostate cancer.


METHODS
From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-4, prostate-specific antigen [PSA] <150 ng/ml) received RT and 4 mo of goserelin and then were randomized to no additional therapy (arm 1) or 24 mo adjuvant goserelin (arm 2) in a phase 3 trial (Radiation Therapy Oncology Group [RTOG] 92-02). Cox regression analyses were performed to evaluate the relationship between treatment arm and cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes (DM), race, PSA, Gleason score, and stage.


RESULTS
After median follow-up of 8.1 yr, 185 cardiovascular-related deaths had occurred. No increase in cardiovascular mortality occurred for men receiving a longer duration of goserelin. At 5 yr, cardiovascular mortality for men receiving longer-term adjuvant goserelin was 5.9% versus 4.8% with short-term goserelin (Gray's p=0.16). In multivariate analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR]=1.09; 95% confidence interval [CI], 0.81-1.47; p=0.58; when censoring at time of salvage goserelin, HR=1.02, 95%CI, 0.73-1.43; p=0.9). Traditional cardiac risk factors, including age, prevalent CVD, and DM, were significantly associated with greater cardiovascular mortality.


CONCLUSIONS
Longer duration of adjuvant GnRHa therapy does not appear to increase cardiovascular mortality in men with locally advanced prostate cancer.
Efstathiou
Jason A
JA
Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom Street, Boston, MA 02114, USA. jefstathiou@partners.org
Bae
Kyounghwa
K
Shipley
William U
WU
Hanks
Gerald E
GE
Pilepich
Miljenko V
MV
Sandler
Howard M
HM
Smith
Matthew R
MR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000401:mortality*; D005485:Flutamide / Q000009:adverse effects*; D017273:Goserelin / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013997:Time Factors
D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D005485:Flutamide