Journal of the National Cancer Institute Advance Access originally published online on October 9, 2007
JNCI Journal of the National Cancer Institute 2007 99(20):1516-1524; doi:10.1093/jnci/djm168
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© The Author 2007. Published by Oxford University Press.
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Androgen Deprivation Therapy for Localized Prostate Cancer and the Risk of Cardiovascular Mortality
Affiliations of authors: Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA (HKT); Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA (AVD); Department of Urology, University of California, San Francisco, CA (NS, PRC); Department of Statistics, University of Connecticut, Storrs, CT (MHC)
Correspondence to: Henry K. Tsai, MD, Harvard Radiation Oncology Program, 375 Longwood Ave, Boston, MA 02215 (e-mail: hktsai{at}post.harvard.edu).
Background: We investigated whether androgen deprivation therapy (ADT) use is associated with an increased risk of death from cardiovascular causes in patients treated for localized prostate cancer.
Methods: From the Cancer of the Prostate Strategic Urologic Research Endeavor database, data on 3262 patients treated with radical prostatectomy and 1630 patients treated with external beam radiation therapy, brachytherapy, or cryotherapy for localized prostate cancer were included in this analysis. Competing risks regression analyses were performed to assess whether use of ADT was associated with a shorter time to death from cardiovascular causes after controlling for age (as a continuous variable) and the presence of baseline cardiovascular disease risk factors. All tests for statistical significance were two-sided.
Results: The median follow-up time was 3.8 years (range = 0.1–11.3 years). Among the 1015 patients who received ADT, the median duration of ADT use was 4.1 months (range = 1.0–32.9 months). In a competing risks regression analysis that controlled for age and risk factors for cardiovascular disease, both ADT use (adjusted hazard ratio [HR] = 2.6; 95% confidence interval [CI] = 1.4 to 4.7; P = .002) and age (adjusted HR = 1.07; 95% CI = 1.02 to 1.1; P = .003) were associated with statistically significantly increased risks of death from cardiovascular causes in patients treated with radical prostatectomy. Among patients 65 years or older treated with radical prostatectomy, the 5-year cumulative incidence of cardiovascular death was 5.5% (95% CI = 1.2% to 9.8%) in those who received ADT and 2.0% (95% CI = 1.1% to 3.0%) in those who did not. Among patients 65 years or older treated with external beam radiation therapy, brachytherapy, or cryotherapy, ADT use was associated with a higher cumulative incidence of death from cardiovascular causes, but the difference did not reach statistical significance.
Conclusions: The use of ADT appears to be associated with an increased risk of death from cardiovascular causes in patients undergoing radical prostatectomy for localized prostate cancer.
| CONTEXT AND CAVEATS Prior knowledge Androgen deprivation therapy (ADT) is increasingly being used in combination with local therapy to treat patients with high-risk localized prostate cancer. However, ADT can lead to conditions that are included in the metabolic syndrome, which increases the risk of coronary artery disease. Study design Observational retrospective study using data from the Cancer of the Prostate Strategic Urologic Research Endeavor registry of patients with biopsy-proven prostate adenocarcinoma. Contribution ADT use appears to be associated with a statistically significantly increased risk of death from cardiovascular causes among patients aged 65 years or older undergoing radical prostatectomy for localized prostate cancer. The 5-year cumulative incidence of cardiovascular death was 5.5% among patients who received ADT and 2.0% among those who did not. Among patients aged 65 years or older treated with external beam radiation therapy, brachytherapy, or cryotherapy, ADT use was associated with an increased cumulative incidence of death from cardiovascular causes, but the increase was not statistically significant. Implications Careful cardiovascular evaluation and intervention are advisable before initiating ADT in patients with localized prostate cancer. Limitations The study had a relatively short follow-up with few fatal cardiovascular events observed. All possible risk factors for cardiovascular death could not be controlled for because of the study's retrospective nature.
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Manuscript received January 18, 2007; revised August 3, 2007; accepted August 24, 2007.
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J Natl Cancer Inst 2007 99: 1497.
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