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Prostate Cancer Prevention

Given the fact that the exact etiology of prostate cancer is unknown, it is very difficult and rather impossible at this stage to prevent prostate cancer.  

At the same time, available knowledge about the risk factors for prostate cancer, incidence statistics, and prevalence potentially allows us to better manage our life style and definitely decrease the incidence of prostate cancer.

The long molecular pathogenesis and the ensuing delayed latency also favorably argue that modifiable factors can possibly be manipulated to decrease the risk of prostate cancer.

Diet
It is highly recommended by all physicians and the American Cancer Society to follow a regimen that is adequate in quantity and quality to ensure healthy weight maintenance. A diet rich in plant sources and limited on red meats (inclusive of high-fat and processed meats) is beneficial in lowering risk.

chemopreventive-agents

Carbohydrate sources should categorically come from whole grains and five or more servings of fruits per day are prescribed. Even though well processed clinical data is missing, LYCOPENE, an antioxidant ingredient has long been considered to possess robust anti-carcinogenic properties. Watermelon, pink grapefruit and tomatoes (Lycopersicon esculentum is the scientific name of tomato and derives its origin from the active ingredient) (raw, cooked or sauced) are the prime food source for lycopene.

Vitamin and Mineral Supplements
A study, called Selenium and Vitamin E Cancer Prevention Trial (SELECT), was conducted (starting from July, 2001) among a randomized group of 35,000 males to study the efficacy of these supplements in lowering the risk of prostate cancer. Unfortunately, initial analysis of the data obtained from the study candidly showed (against the prevalent belief) that neither selenium nor vitamin E has any positive effect as a risk lowering factor in prostate cancer. The final analysis will be completed in 2013. Current research is additionally focusing on isoflavones, the active ingredient of soy proteins, and its usage to lower the risk of prostate cancer.

Green Tea
Native Asian men with a high dietary supplement of green tea have been shown to be at a lower risk of prostate cancer. Polyphenols, the active ingredient in green tea, has been shown by researchers to inhibit cell growth and further dysregulate cell cycle-an empirical pre-requisite for the onset of any form of tumorigenesis. But the precise molecular mechanism for such action has not yet been elucidated. Large scale epidemiological study using green tea has not been reported.

Chemoprevention (PCPT and REDUCE)
Given that histological lesions seen in prostatic intraepithelial neoplasia (PIN), proliferative inflammatory atrophy, and atypical small acinar proliferation are representative of an intermediary pathological state between a normal and cancerous prostate cancer cell, drugs targeting the onset of the disease are conceivable. The Prostate Cancer Prevention Trial (PCPT) was initiated at the behest of the National Cancer Institute to look at drugs that can lower the risk of prostate cancer. It is imperative that any form of chemoprevention will be secondary to a proper lifestyle with well-defined diet and exercise regimen and refraining from smoking.

Basis of the PCPT: Androgens, male sex hormones, are required for the development of prostate cancer. People with a congenital deficiency of the enzyme, 5α-reductase type 2, are refractory to prostate cancer (very similar to sickle cell anemia patients being refractory to malaria). Thus the hypothesis was that a drug, finasteride, targeting this enzyme in healthy individuals should lower the risk of prostate cancer.

The study: A randomized population of 18, 882 healthy men [normal digital rectal examination (DRE) and a prostate-specific antigen (PSA) level less than 3.0 ng/mL) were selected for this 7 year study, which started in 1993. The study group was divided into two groups, one group receiving 5 mg/day finasteride and the other was the placebo group. The groups were monitored by DRE and PSA levels. Abnormal results in either were followed up by prostate gland biopsy.

What the study showed? The Data and Safety Monitoring Committee ended the study 15 months before the scheduled end as the findings were striking upto that point. Of note, even though the study was terminated all candidates were monitored for long term survival rate. The relative risk of prostate cancer decreased from 24.4% in the placebo group to 18.4% in the finasteride-treated group. The overall prevalence of prostate cancer was shot down by 24.8%. The observed risk reduction was not affected by epidemiological factors (age, race, family history). But the downside was that the prostate tumors that were forming in the finasteride group were high grade and more aggressive (6.4%) compared to the ones formed in the placebo group (5.1%). Hence, even though the positive effect of finasteride was apparent it was not well accepted by the medical community. But research on finasteride continued into the new millennium and finally in 2008 researchers showed that finasteride were not aiding in formation of aggressive tumors, rather it was helping in detection of the same. Concurrently, it was also shown that finasteride decreased the risk of latent (indolent), slow-growing or high grade, aggressive tumors.

Finasteride is still not a FDA approved medication for lowering risk of prostate cancer. The potential benefits weighed against prospective risks in the right perspective will ultimately determine whether it is accepted as a therapeutic regimen by the FDA. A comparison can be drawn from the approved usage of Tamoxifen in patients at high-risk of breast cancer, even though Tamoxifen usage can lead to cardiac disease, endometrial cancer or cataracts. Another 5α-reductase type 2 inhibitor, Dutasteride, was studied over a span of 4 years in a study designated the Reduction by Dutasteride of Prostate Cancer Events (REDUCE). Results were similarly encouraging as PCPT.

The Pipeline
Toremifene, an anti-estrogen drug, is now part of a large randomized study to look at its prostate cancer risk lowering capacity. Cyclo-oxygenase inhibitors are also being potentially touted for clinical trials. The focus is on antioxidants with antiandrogenic effects, as these are the ones with the most promise (based on the findings of the PCPT and REDUCE studies). The recent discovery of the XMRV as a potential causative agent of prostate cancer also opens an avenue of a vaccine against the disease. Ultimately the trials have to generate adequate and well controlled data that will justify usage of dietary, nutritional, or oral supplement that will significantly reduce the risk and thus lower and prevent the incidence prostate cancer. Current research holds much promise and the future looks bright that a preventive measure will be discovered.

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