Some Prostate Cancers Unaffected, Others Prevented With 5ARIs

Mark A. Preston, MD

Investigators say they have found no association between the use of 5-alpha-reductase inhibitors (5ARIs) and the risk of developing high-grade or lethal prostate cancer.

Furthermore, such medications are associated with a decreased risk of developing overall, low-grade, and Gleason 7 prostate cancer, according to the results, reported at the 108th Annual Meeting of the American Urological Association (AUA).

Mark A. Preston, MD, of Harvard Medical School and Massachusetts General Hospital in Boston, and colleagues elsewhere examined the association between finasteride use for prostate cancer chemoprevention and the development of total, high-grade, or lethal prostate cancer in men enrolled in the Health Professionals Follow-up Study (HPFS).

The ongoing HPFS is a large prospective cohort of United States male health professionals who were age 40 to 75 years at baseline in 1986.

Preston, a urologic oncology fellow, pointed out that 5ARIs, which are widely used to treat benign prostatic hyperplasia, were shown to reduce prostate cancer incidence by 23% to 25% in two randomized chemoprevention trials: the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial.

In prior trials of such treatments, risk reduction was largely explained by a decreased incidence of Gleason ≤ 6 cancer, and an increased risk of high-grade Gleason 8-10 disease was found. Because of the increased risk of high-grade prostate cancer reported in those trials, preventive strategies with 5ARIs have not been embraced by clinicians and patients.

The relevance of the observed increased incidence of high-grade cancer on lethal outcomes has not been clear, Preston added.

The present analysis included 38,430 men who were cancer-free in 1996 and completed questionnaires on finasteride use every 2 years until 2010. Overall, 2920 (7.6%) men reported using finasteride during this time period.

The analysis adjusted for potential confounders, including age; time period; recent smoking history; race; family history of prostate cancer; vigorous physical activity; body mass index; height; history of diabetes mellitus; history and intensity of prostate-specific antigen (PSA) testing; history of physical examinations; history of prostate biopsy or rectal ultrasound; treatment with statins, digoxin, alphablockers, aspirin, and nonsteroidal anti-inflammatory agents; saw palmetto use; and vasectomy.

During 452,576 person-years of follow-up, 3710 prostate cancer cases were documented, 578 of which were advanced and 463 of which were high grade.

After adjusting for confounders, the use of finasteride was associated with significantly lower risk of total disease, Gleason 7, and low-grade disease.

The multivariable-adjusted relative risk was 0.77 (95% CI, 0.65-0.90) for total disease, 0.66 (95% CI, 0.49-0.89) for Gleason 7 disease, and 0.73 (95% CI, 0.57-0.94) for low-grade disease. 5ARI use was not associated with higher risk of prostate cancer or lethal disease.

“It was reassuring to find that the overall prostate cancer risk reduction of 23% with 5ARI use was very similar to the reduction seen in the two randomized chemoprevention trials,” Preston said.

He pointed out that the strengths of the study he presented include its prospective design, large sample size, and lengthy follow-up.

In addition, study participants were health professionals and therefore knowledgeable and motivated, which can be expected to boost the reliability of the data, he said.

Preston, MA, Wilson K, CoSeo-Markts, et al. The association between finasteride use and high-grade or lethal prostate cancer. Presented at: the Annual Meeting of the American Urological Association; May 4-8, 2013; San Diego, CA. Abstract 228.