Can modifications in dietary intake affect survival in men with prostate cancer? Despite robust data indicating that dietary constituents may be substantially associated with the natural history of prostate cancer, there remains a paucity of Level I evidence on which to base clinical recommendations.1
Randomized clinical trials of dietary supplements have failed to yield demonstrable benefits. For example, the Selenium and Vitamin E Cancer Prevention Trial (SELECT)—a randomized, placebo-controlled study of more than 34,000 men randomized to once daily vitamin E (400 IU), selenium (200 mcg/day), both, or placebo—showed that neither vitamin E nor selenium had any observable benefit in preventing incident prostate cancer. In fact, the study showed a nonsignificant increased risk of prostate cancer and diabetes for patients taking those amounts of vitamin E (p=0.06) and selenium (p=0.06), respectively.2 Other studies have yielded similar results for selenium, vitamin E, and vitamin C.2,3
A new approach
These disappointing observations have prompted researchers to reassess the prior micronutrient models of prostate cancer therapy and refocus their efforts on developing viable interventions based on broad patterns of dietary practice. Epidemiological studies suggest that altering nutritional intake—specifically, switching to a diet that emphasizes vegetable intake and de-emphasizes meat and fat intake—may inhibit prostate cancer initiation and clinical progression.4-6 Experimental studies in prostate cell line and animal models demonstrate that components of cruciferous vegetables (such as kale, broccoli, and turnips) and carotenoids (such as tomatoes and carrots) induce apoptosis of prostate cancer cells, inhibit carcinogenesis, and promote the expression of cytoprotective enzymes in prostate tissue.7-9
Clinical evidence supporting these observational and preclinical data, however, is limited. Three small studies have evaluated diet change as a therapy for prostate cancer, one of which suggested a beneficial effect for a vegetable-intense diet in a small number of patients with low-stage, low-grade disease.10-12 However, whereas this intensive lifestyle intervention also included dietary supplements, exercise, stress management, and support group participation, more definitive studies, testing feasible yet robust diet-based interventions capable of being implemented and sustained on a larger scale, are needed.11
Active surveillance for prostate cancer and dietary interventions
Nearly 50 percent of newly diagnosed prostate cancer patients in the U.S. present with localized, early stage, relatively indolent disease.13 A substantial proportion of these patients receive unnecessarily aggressive treatment with surgery, radiation, or hormone-based treatments.13,14 These therapies produce considerable urinary, bowel, and sexual morbidities, and their impact on prostate cancer-specific or overall mortality in patients with less aggressive cancers is not clear.15-17
Active surveillance, which entails careful monitoring of selected patients with early stage prostate cancer, may provide a viable and safe alternative to more aggressive treatments.18,19 Approximately 35 percent of patients on active surveillance will progress within five years, while many others will opt for intervention even though they do not meet the objective criteria for progression.18Reducing the number of active surveillance patients who progress or choose treatment represents an important opportunity to minimize treatment-associated morbidity, improve quality of life, and contain health care costs among appropriate prostate cancer patients.
Dietary interventions represent an opportunity to potentially reduce the number of prostate cancer patients who progress on active surveillance. We have designed and successfully pilot-tested a dietary intervention for prostate cancer patients based on well-established sociological principles.20 This intervention, which involves telephone-based counseling, produced robust diet changes and led to increased plasma carotenoid levels—biomarkers for vegetable intake—in patients with localized prostate cancer on active surveillance.
CALGB 70807: The Men’s Eating and Living (MEAL) Study
The MEAL Study is a randomized clinical trial testing the effect of a high-vegetable diet on disease progression in prostate cancer patients on active surveillance (see figure and table). It is the first national trial of a nonsupplement dietary intervention for prostate cancer and one of the first major studies of an intervention targeted for active surveillance patients. A total of 464 patients will be enrolled and monitored, each for up to two years. MEAL uses the same telephone-based counseling intervention validated in the pilot study.20 Patients will be randomized to a telephone counseling program to assist with their dietary change (Group A) or to receive printed materials based on U.S. Department of Agriculture recommendations (Group B). The target daily intake for Group A is: seven servings of vegetables (three cruciferous, two tomatoes/tomato products, two other vegetables); two servings of whole grains; two servings of fruit; and one serving of beans or other legumes.
The primary goal of MEAL will be to measure disease progression defined by total prostate-specific antigen (PSA), PSA doubling time, and pathology on repeat prostate biopsy. Secondary measures will include treatment seeking, patient anxiety, health-related quality of life, and tissue biomarkers.
Therapeutic dietary modification would potentially promulgate a novel paradigm for lower-risk prostate cancer akin to diet alterations for non–insulin-dependent diabetes: medical management, without curative intent, of a chronic disease state. There is widespread interest in diet as a possible factor in disease risk and progression. The limited data available suggest that a diet emphasizing plant products and de-emphasizing animal products protects against carcinogenesis and cancer progression. Experimental consideration confirming or refuting the impact of diet, however, is needed. The MEAL study, which will follow prostate cancer patients under expectant management, will provide important data on the actual, short-term impact of the adoption of a diet that increases vegetable intake and limits meat and dairy intake.
- Silberstein J, Parsons JK. Current concepts in diet and prostate cancer. Aging Health. 2008;4(5):495-505.
- Silberstein JL, Parsons JK. Prostate cancer prevention: Concepts and clinical recommendations. Prostate Cancer Prostatic Dis. 2010;13(4):300-306.
- Marshall JR, Tangen CM, Sakr WA, Wood DP Jr, Berry DL, Klein EA, Lippman SM, Parnes HL, Alberts DS, Jarrard DF, Lee WR, Gaziano JM, Crawford ED, Ely B, Ray M, Davis W, Minasian LM, Thompson IM Jr. Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia: SWOG S9917. Cancer Prev Res (Phila). 2011;4(11):1761-1769.
- Sonn GA, Aronson W, Litwin MS. Impact of diet on prostate cancer: A review. Prostate Cancer Prostatic Dis. 2005;8(4):304-310.
- Stevens VL, Rodriguez C, Pavluck AL, McCullough ML, Thun MJ, Calle EE. Folate nutrition and prostate cancer incidence in a large cohort of US men. Am J Epidemiol. 2006;163:989-996.
- Richman EL, Carroll PR, Chan JM. Vegetable and fruit intake after diagnosis and risk of prostate cancer progression. Int J Cancer. 2012;131(1):201-210.
- Barber NJ, Zhang X, Zhu G, Pramanik R, Barber JA, Martin FL, Morris JD, Muir GH. Lycopene inhibits DNA synthesis in primary prostate epithelial cells in vitro and its administration is associated with a reduced prostate-specific antigen velocity in a phase II clinical study. Prostate Cancer Prostatic Dis. 2006;9(4):407-413.
- Brooks JD, Paton VG, Vidanes G. Potent induction of phase 2 enzymes in human prostate cells by sulforaphane. Cancer Epidemiol Biomarkers Prev. 2001;10(9):949-954.
- Singh AV, Xiao D, Lew KL, Dhir R, Singh SV. Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis. January 2004;25(1):83-90.
- Spentzos D, Mantzoros C, Regan MM, Morrissey ME, Duggan S, Flickner-Garvey S, McCormick H, DeWolf W, Balk S, Bubley GJ. Minimal effect of a low-fat/high soy diet for asymptomatic, hormonally naive prostate cancer patients. Clin Cancer Res. 2003;9(9):3282-3287.
- Ornish D, Weidner G, Fair WR, Marlin R, Pettengill EB, Raisin CJ, Dunn-Emke S, Crutchfield L, Jacobs FN, Barnard RJ, Aronson WJ, McCormac P, McKnight DJ, Fein JD, Dnistrian AM, Weinstein J, Ngo TH, Mendell NR, Carroll PR. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005;174(3):1065-1069; discussion 9-70.
- Saxe GA, Major JM, Nguyen JY, Freeman KM, Downs TM, Salem CE. Potential attenuation of disease progression in recurrent prostate cancer with plant-based diet and stress reduction. Integr Cancer Ther. 2006;5(3):206-213.
- Cooperberg MR, Lubeck DP, Meng MV, Mehta SS, Carroll PR. The changing face of low-risk prostate cancer: Trends in clinical presentation and primary management. J Clin Oncol. 2004;22(11):2141-2149.
- Carroll PR. Early stage prostate cancer—Do we have a problem with over-detection, overtreatment or both? J Urol. 2005;173(4):1061-1062.
- Miller DC, Sanda MG, Dunn RL, Montie JE, Pimentel H, Sandler HM, McLaughlin WP, Wei JT. Long-term outcomes among localized prostate cancer survivors: Health-related quality-of-life changes after radical prostatectomy, external radiation, and brachytherapy. J Clin Oncol. 2005;23(12):2772-2780.
- Potosky AL, Davis WW, Hoffman RM, Stanford JL, Stephenson RA, Penson DF, Harlan LC. Five-year outcomes after prostatectomy or radiotherapy for prostate cancer: The prostate cancer outcomes study. J Natl Cancer Inst. 2004;96(18):1358-1367.
- Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA. 2005;293(17):2095-2101.
- Klotz L. Active surveillance for prostate cancer: For whom? J Clin Oncol. 2005;23(32):8165-8169.
- Warlick C, Trock BJ, Landis P, Epstein JI, Carter HB. Delayed versus immediate surgical intervention and prostate cancer outcome. J Natl Cancer Inst. 2006;98(5):355-357.
- Parsons JK, Newman VA, Mohler JL, Pierce JP, Flatt S, Marshall J. Dietary modification in patients with prostate cancer on active surveillance: A randomized, multicentre feasibility study. BJU Int. 2008;101(10):1227-1231.