Androgen-deprivation therapy (ADT) is the standard initial treatment for men with metastatic prostate cancer, yet the majority of men in the U.S. who receive ADT have nonmetastatic disease. Recently, the FDA asked the manufacturers of gonadotropin-releasing hormone (GnRH) agonists to include warnings about the potential risks for diabetes and cardiovascular diseases associated with their products; links between GnRH agonists and fracture risk have also been demonstrated (JW Oncol Hematol Aug 11 2009).

Now, investigators have assessed the potential association between colorectal cancer (CRC) and the use of ADT (with GnRH agonists or orchiectomy). The researchers analyzed Surveillance, Epidemiology, and End Results (SEER) Medicare data for 107,859 men (age, 67) who received initial diagnoses of prostate cancer from 1993 through 2002.

During a mean follow-up of 59.4 months after diagnosis, 2035 patients developed CRC. The incidence of CRC per 1000 person-years was 6.3 for men who underwent orchiectomy, 4.4 for men who received GnRH agonist therapy, and 3.7 for men who received no ADT. The adjusted hazard ratio for orchiectomy versus no ADT was 1.37 (95% confidence interval, 1.14–1.66). CRC risk increased with duration of GnRH agonist use: For 13 to 24 months of GnRH agonist use, the AHR versus no ADT was 1.19 (95% CI, 1.00–1.41), and, for 25 months of GnRH agonist use, the AHR versus no ADT was 1.31 (95% CI, 1.12–1.53).

Editor's Comment: An accompanying editorial notes that obesity is consistently associated with excess risk for CRC in men. Obese men tend to have lower testosterone levels than nonobese men, and both hyperinsulinemia and insulin resistance might be causally linked to obesity and development of CRC. The editorialists also speculate that the increased risk for CRC that was evident so soon after ADT use in the current analysis might reflect the influence of hormones on relatively late processes of carcinogenesis. As the list of risks associated with ADT use increases, the appropriate selection of patients for ADT — as well as the use of aggressive lifestyle and diet modification in those who require ADT— becomes increasingly important.

Robert Dreicer, MD, MS, FAC
Published in Journal Watch Oncology and HematologyDecember 21, 2010