Men treated with long-term androgen deprivation therapy (ADT) for prostate cancer are at increased risk for colorectal cancer, according to a study released in the Journal of the National Cancer Institute.
Androgen deprivation, either through gonadotropin-releasing hormone (GnRH) agonists or orchiectomy, is a common treatment for prostate cancer. Androgen, however, has been shown in animal models to provide a protective effect against colorectal carcinogenesis. In addition, ADT has been associated with development of hyperinsulinemia, diabetes mellitus, and obesity, all of which are known risk factors for colorectal cancer.
Gillessen and colleagues identified 107,859 men in the SEER-Medicare database who were diagnosed with prostate cancer from 1993 to 2002 and with follow-up available through 2004. Cox proportional hazards regression was used to determine the influence of ADT on development of colorectal cancer as a second primary cancer.
Orchiectomy was associated with the highest unadjusted incidence rate of colorectal cancer (6.3 per 1000 person-years; 95% CI, 5.3-7.5), followed by GnRH agonist therapy (4.4 per 1000 person-years; 95% CI, 4.0-4.9). No androgen deprivation had the lowest incidence rate (3.7 per 1000 person-years; 95% CI, 3.5-3.9). After adjustment for patient and prostate cancer characteristics, there was a statistically significant dose–response effect (P = .010) with an increasing risk of colorectal cancer associated with increasing duration of androgen deprivation. Compared with the absence of these treatments, there was an increased risk of colorectal cancer associated with use of GnRH agonist therapy for 25 months or longer (HR, 1.31; 95% CI, 1.12-1.53) or with orchiectomy (HR, 1.37; 95% CI, 1.14-1.66).
The authors concluded that men with prostate cancer who are receiving or contemplating ADT should carefully weigh the small risk of developing colorectal cancer with the potential benefits of ADT, especially in settings where clinical trials have shown improvement in overall survival with ADT.