Preventing Prostate Cancer Becoming a Reality

Roxanne Nelson

September 25, 2007 — Prostate cancer is a leading cause of cancer death among men in Western nations, and while risk factors such as age, race, and family history cannot be controlled, a growing body of data suggests that it may be a preventable disease. In a review paper published online September 24 in Cancer, Neil Fleshner, MD, and Alexandre Zlotta, MD, PhD, both from the University of Toronto, in Ontario, discuss potential prevention strategies for the disease as well as the need to continue investigations into the molecular pathways that develop, sustain, and lead to the progression of malignant cells in the prostate.
"We are learning so much about prostate cancer all the time," Dr. Fleshner told Medscape Oncology. "We have proven now, with our experience with finasteride, that prostate cancer is a preventable disease on some level. What is remarkable about this field is that it didn’t exist 10 years ago, and now it has exploded. What started as epidemiological observations has moved into a body of credible science that is suggesting that we are on the cusp of being able to prevent prostate cancer."
Preventing cancer is preferable to early detection and treatment, Dr. Fleshner pointed out. "I think most everyone would agree that an effective way of preventing this disease is far more advantageous on a population level than searching out cancers and destroying them."
Prostate cancer is the most common malignancy found in males, and in some aspects, appears to be a part of the natural aging process. Autopsies have indicated that by the time men enter their fourth decade of life, about a third already have small malignant prostate tumors. By approximately age 60 years, these small carcinomas can be found in an estimated 60% of all men. The rates of these occult cancers at autopsy seem similar worldwide, despite the variation in prostate cancer–related mortality rates.
The overall risk of dying from prostate cancer remains quite low, and Dr. Fleshner explained that the major cause of death for men with prostate cancer is heart disease. With such a large discordance between histologic incidence and mortality, there is a high risk for overdetection and overtreatment. Aggressive interventions for early-stage disease have improved overall survival, but many patients receive unnecessary treatment and then must contend with adverse effects such as sexual dysfunction and urinary problems.
The whole concept of preventing prostate cancer is a relatively new field of study, Dr. Fleshner explained, and clinical trials aimed at prevention were not even contemplated until 2 decades ago. "We have several major clinical trials that will be maturing in the next 1 to 5 years, so we are on the cusp of moving preventive agents into the clinical area, assuming that 1 or more of the results will be positive."
In this paper, Drs. Fleshner and Zlotta review prevention strategies that are currently under study. Recent trials have focused on a number of interventions, including the use of dietary fat reduction and supplementation with vitamins D, E, and selenium, as well as consumption of soy, green tea, and food products rich in lycopene. They also examined preventive strategies using pharmacological agents such as cyclooxygenase inhibitors, antiestrogens, and 5-alpha-reductase inhibitors. Clinical trials examining pharmaceutical interventions have shown that 5-alpha-reductase inhibitors such as finasteride and dutasteride, along with the selective estrogen-receptor modifier toremifene, have demonstrated promising results in decreasing the number of prostate cancers at biopsy. As an example, dutasteride was found to decrease the number of malignant biopsies among patients with benign prostatic hypertrophy by 50%.
Case-control, ecologic, and cohort studies have consistently demonstrated an association between dietary fat and prostate cancer. Studies investigating the use of dietary supplements in preventing prostate cancer have also shown promising results. A randomized study evaluating selenium's role in preventing prostate cancer found that, over a 10-year period, the incidence of the disease was reduced by 49% among the participants who used selenium supplements. A surprising result of the Alpha-Tocopherol Beta-Carotene (ATBC) trial, which randomized 19,000 Finnish men to vitamin E, beta-carotene, both, or placebo to determine whether certain vitamin supplements would prevent lung cancer, showed a one-third reduced chance of prostate cancer among men who took vitamin E. Other studies suggest that vitamin E may reduce the risk of prostate cancer among smokers.
The efficacy of other nutritional approaches, such as green tea, has been less clear, the researchers report. Studies evaluating the efficacy of soy and lycopene are ongoing.
"Right now, the most promising preventive agents are the 5-alpha-reductase inhibitors, only because we have proof that they work," said Dr. Fleshner. "We have a large trial under way right now that is evaluating dutasteride, called the Reduction by Dutasteride of Prostate Cancer Events (REDUCE), and that may be the most promising to date."
Another pharmacologic study is evaluating the efficacy of toremifene in preventing high-grade prostatic intraepithelial neoplasia. "Altogether, the results of these studies can have a major impact on the way prostate cancer is dealt with," said Dr. Fleshner
Dr. Fleshner owns shares in Bioadvantex Pharma.
Cancer. Published online September 24, 2007.