TABLE 2.
DATA SOURCE | STUDY POPULATION | EVENTS | TIME TO CARDIOVASCULAR MORBIDITY: AHR (95% CI), P | TIME TO CARDIOVASCULAR DEATH: AHR OR POINT ESTIMATES (95% CI), P |
---|---|---|---|---|
Observational studies | ||||
SEER/Medicare1 | 73,196 Men aged >65 y with local/regional prostate cancer | 3917 MIs; 15,116 incident cases of coronary heart disease; 3301 sudden cardiac deaths | MI (ADT vs no ADT) 1.11 (1.01-1.21), .03; coronary heart disease (ADT vs no ADT) 1.16 (1.10-1.21), .001 | Sudden cardiac death or life-threatening ventricular arrhythmia (ADT vs no ADT) 1.16 (1.05-1.27), .004 |
SEER/Medicare2 | 22,816 Men aged >65 y with prostate cancer, all stages | ≈4321 Cardiovascular events (definition of cardiovascular event not provided) | Cardiovascular event (ADT vs no ADT) 1.20 (1.15-1.26), <.05 | — |
CaPSURE4 | 4892 Men with localized prostate cancer, all ages, including 3262 patients who had radical prostatectomy and 1630 men who had radiation | 131 Total cardiovascular deaths; 61 deaths in radical prostatectomy group, 70 in radiation group | — | Radical prostatectomy group (ADT vs no ADT) 2.6 (1.4-4.7), .002; Radiation group (ADT vs no ADT) 1.2 (0.8-1.9), .40 |
Nanda et al36 | 5077 With localized or locally advanced prostate cancer. Patients treated or not treated with adjuvant ADT on the basis of clinical indications | 419 All-cause deaths; Subgroup of patients with CAD-induced CHF or MI had 25/95 deaths in ADT-treated patients;18/161 deaths in non–ADT- treated patients | — | No difference in all-cause mortality in entire cohort, 11.1% vs 7.0% 1.08 (0.88-1.33); Greater mortality in the subgroup of patients with CAD treated with ADT (vs no ADT) 1.96 (1.04-3.71) |
Alibhai et al34 | Matched-cohort study of 19,079 prostate cancer patients treated with at least 6 mo of ADT | 949 MIs in ADT users, 1085 MIs in nonusers; 399 sudden cardiac deaths in ADT users, 436 in nonusers | Diabetes (ADT vs no ADT) 1.16 (1.11-1.21); MI (ADT vs no ADT) 0.91 (0.84-1.00); Sudden cardiac death (ADT vs no ADT) 0.96 (0.83-1.10) | — |
Postrandomization analyses | ||||
Pooled analysis of RCTs3 | 1372 Men of all ages with localized prostate cancer treated with radiation who enrolled in 1 of 3 ADT trials in which patients received 0 vs 3 vs 6 mo, 3 vs 8 mo, or 0 vs 6 mo of ADT | 51 Cardiovascular deaths (due to MI) | — | Shorter time to fatal MI in those ≥65 y treated with 6 mo of ADT compared with those not treated with ADT (P=.017). Effect seen only in men aged ≥65 y. |
RTOG 861012 | 456 Men of all ages with locally advanced prostate cancer treated with radiation | 348 Total deaths; 57 cardiovascular deaths | — | Estimates of fatal MI at 10 y with ADT 12.5 (8-17) Estimates of fatal MI at 10 y with no ADT 9.1 (5.3-13), .32 |
RTOG 920232 | 1554 Men with locally advanced prostate cancer all treated with radiation and 4 mo of ADT who were then randomized to no additional ADT or 24 additional mo of ADT | 765 Total deaths; 185 cardiovascular deaths | — | Cardiovascular mortality (28 total mo of ADT vs 4 mo of ADT) 1.09 (0.81-1.47), .58 |
EORTC 3089137 | 985 Men of all ages with locally advanced or node-positive disease not suitable for local curative treatment assigned to immediate vs deferred ADT | 541 Total deaths; 185 cardiovascular deaths | — | Cardiovascular mortality after median 7.8-y follow-up: 17.9% in immediate-ADT group vs 19.7% in deferred-ADT group (P not given, but percentage was lower in the immediate-ADT group.) |
RTOG 85-3133 | 945 Men of all ages with locally advanced or node-positive prostate cancer treated with EBRT and then randomized to either long-term adjuvant ADT (Arm 1) or ADT therapy only for local and/or distant disease recurrence (Arm 2). Arm 1 median ADT Rx 4.2 y. In Arm 2, 64% of patients received salvage ADT a median of 3.0 y after EBRT. | 574 Total deaths; 117 cardiovascular deaths | — | Cardiovascular mortality at 9 y: Arm 1 (EBR with ADT) =8.4%; Arm 2 (“salvage” ADT for recurrence)=11.4% (P=.17). Arm 2 vs Arm 1 0.73 (0.47-1.15), .16. No significant treatment-related effect found after censoring for salvage ADT |
D’Amico et al11 | 206 Men with localized but unfavorable-risk prostate cancer randomized to RT alone or RT plus 6 mo of ADT | 74 Total deaths (44 in the RT-alone group and 30 in the RT plus ADT group; 13 cardiac deaths in each treatment group | — | In patients treated with ADT, there were more cardiac deaths (11 vs 2) in men with moderate to severe comorbidity than in those without such comorbidity, which led to a loss of the survival benefit in this subgroup. |
Randomized study analysis | ||||
EORTC 2296135 | 1113 Men with locally advanced prostate cancer randomized to brachytherapy and a total of 6 mo of ADT or brachytherapy and a total of 3 y of ADT | 132 Deaths in short-term group, 98 deaths in long-term group; 31 cardiac deaths in short-term group, 25 in long-term group | — | No significant difference in fatal cardiac events (4.0% in short-term group; 3.0% in long-term group |
AHR indicates adjusted hazard ratio; CI, confidence interval; SEER, Surveillance, Epidemiology, and End Results; CaPSURE, Cancer of the Prostate Strategic Urologic Research Endeavor, a longitudinal, observational registry of men with biopsy-proven prostate cancer; MIs, myocardial infarctions; ADT, androgen-deprivation therapy; CAD, coronary artery disease; CHF, congestive heart failure; RCTs, randomized controlled trials; RTOG, Radiation Therapy Oncology Group; EORTC, European Organization for Research and Treatment of Cancer; EBRT, external-beam radiation therapy; RT, radiation therapy; Rx, treatment.