Commentary by Christopher Tully MD, PGY-1
Faculty Peer Reviewed
An apple a day. . . keeps the prostate cancer away? While it is an overstatement to say that an apple can prevent cancer, the notion of taking “something” to prevent cancer initiation and growth is nothing new. Primary prevention has long been a goal of researchers and physicians with the aim of preventing the morbidity and mortality associated with malignant disease. Prostate cancer is an appropriate choice in studying this topic since we already know our high fat, high cholesterol Western diet contributes to the increased rates of prostate cancer, especially when studied in immigrant populations. The question that then follows is if we can increase prostate cancer rates with our diet, can we also decrease the rates by taking “something” to counteract or neutralize the harmful effects? The substances that have specifically received the most interest are antioxidants, and in the case of prostate cancer, vitamin E and selenium.
Around 10 years ago, it appeared researchers were making progress with prostate cancer and the use of antioxidants in preventing the incidence of prostate cancer. The 1998 ATBC (Alpha-Tocopherol, Beta Carotene) Cancer Prevention Trial enrolled 29,133 male smokers in Finland and showed a 32% decrease in the incidence of prostate cancer and 40% fewer deaths from prostate cancer in those who took vitamin E . Similarly, the 1996 Nutritional Prevention of Cancer trial enrolled 1312 men and women with skin cancer showed 60% fewer cases of prostate caencer in male patients who had taken selenium for 6.5 years . As prostate cancer was not the prespecified primary endpoint in either trial, studies designed to specifically test the benefit of these two antioxidants were organized in order to validate or disprove the results.
While hopes were high, unfortunately, after a decade of waiting, the two major trials designed to answer the question of vitamin E and selenium provided no evidence to warrant supplementation with these antioxidants. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) enrolled over 35,500 men age 50 and older and randomized them to receive vitamin E, selenium or placebo. At the end of an average of 5.5 years of follow up, the hazard ratios for the rates of prostate cancer for selenium were 1.13 (99% CI, 0.95-1.35), for vitamin E were 1.04 (99% CI 0.87-1.24) and for selenium + vitamin E were 1.05% (99% CI 0.88-1.25) vs. 1.00 for placebo. There were also no significant differences in the rates of any of the other prespecified cancer end points (lung, colon or any primary cancer). There was also a small, but not statistically significant increase in the number of prostate cancer cases in the participants taking only vitamin E and a small, but not statistically significant increase in the number of cases of adult onset diabetes in men taking only selenium.
The Physicians’ Health Study II, a randomized, double-blind, placebo-controlled factorial trial, attempted to assess the role of vitamin E and vitamin C (a widely available and consumed antioxident). The trial enrolled over 14,600 male physicians and randomized the participants to receive vitamin C, vitamin E, multivitamin or placebo. At the end of an average of 8 years, the hazard ratios for prostate cancer for vitamin E were 0.97 (95% CI 0.85-1.09) and for vitamin C were 1.02 (95% CI 0.90-1.15). Similarly, there were no significant differences in the rates of any of the other prespecified cancers (lung, colorectal, any primary cancer).
In summary, neither of these large randomized, double-blind, placebo-controlled trials resulted in any significant difference in the rates of prostate cancer (or any cancer). While further data will be presented from both studies, it now appears that neither selenium nor vitamin E will be the answer in the prevention of prostate cancer and that the initial results from the studies a decade ago were due to chance.
The story of vitamin E and selenium provides an interesting insight into how we perceive what it means to be healthy. While the general perception that multivitamins are part of a “healthy lifestyle” and anecdotal evidence of perpetually healthy friends who swear by supplements can convince any skeptic to pop a pill, when assessed in a clinical setting, the clinical evidence is typically absent. In all likelihood, our healthy friends were going to be healthy no matter what and we are just buying into a retrospective analysis that deludes us into thinking this pill can make the difference. I am not trying to deny the worth of multivitamin supplements, but only recommend that before you jump on the bandwagon of the next supplement solution, be sure the evidence is there to support your decision.
Comments by reviewer Theresa Ryan MD, Assistant Professor of Medicine, NYU Division of Medical Oncology:
Prostate cancer is an increasingly important health issue globally. With 679,060 men diagnosed each year, prostate cancers are the fifth most common tumor type worldwide It is estimated that in 2007, prostate cancer will be diagnosed in 218,890 men in the United States alone and that 27,050 will die from their disease. Clearly there is a need not only for improved treatment but also for that “holy grail” of oncology, effective prevention.
To that end the results of these trials are disappointing; neither selenium nor vitamin E supplementation, alone or in combination, produced any reductions in prostate cancer. On the other hand they are a “tour de force” in what they have accomplished. The SELECT trial in particular, being the largest randomized cancer prevention trial ever conducted with robust statistical power; is an impressive model for future prevention trials. In addition, preplanned subgroup analyses will continue to yield hypothesis generating information for years to come.
But now that we have a model, the harder question is “what to test”. The hope of modern oncology is that better understanding of disease will lead to the identification of more rationale targets/molecules to test. And that is the challenge that lies ahead.
As for right now, these trials do answer an important question for our patients “Should I take selenium or vitamin E to prevent prostate canc]er?” The answer is no.
Heinonen OP, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: Incidence and mortality in a controlled trial. Journal of the National Cancer Institute 1998; 90(6):440-446.
 Clark LC, Combs GF Jr., Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Journal of the American Medical Association 1996; 276(24):1957-1963.
 Lippman, S., Klein, E., Goodman, P., and et al. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009; 301 (1)
 Gaziano, M., Glynn, R., Christen, W., and et al. Vitamins E and C in the Prevention of Prostate and Total Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial. JAMA 2009; 301(1)