Efforts to clarify the role of diet and lifestyle on the development and outcomes of prostate cancer (PCa) are highly valuable given the global burden and protracted natural history of the disease. Indeed, PCa is diagnosed in approximately 1.1 million men worldwide annually and is a major contributor to cancer-related mortality, accounting for some 307,000 deaths per year.1 How health behaviors influence PCa outcomes remains controversial. Randomized placebo-controlled trials of individual supplements (such as selenium and vitamin E) have not indicated a clear benefit in the prevention of PCa, and studies of broader exercise or dietary patterns have remained challenging (see Table 1).2,3
Table 1. Review of published and ongoing prospective, randomized controlled trials addressing the role of diet and/or lifestyle in PCa
|Study design||Study||Intervention||Population||Primary finding|
|Participants randomized to once-daily vitamin E, selenium, both, or placebo||SELECT2,11||Selenium and vitamin E||34,887 healthy men without known PCa||Neither vitamin E nor selenium demonstrated benefit in preventing prostate cancer; increased risk associated with vitamin E supplementation|
|Randomized trial testing effect of high-vegetable diet among men managed with active surveillance||MEAL10,12||Dietary change||464 men with clinical-low risk PCa||Accrual completed; awaiting study results|
|Participants randomized to receive alpha-tocopherol, beta-carotene, both, or placebo||ATBC13-15||Alpha-tocopherol, beta-carotene supplementation||29,133 male smokers||At median 6.1 year follow-up, reduction in prostate cancer mortality; in extended follow-up preventive effect of moderate dose alpha-tocopherol, increased risk with beta-carotene|
|Randomization to daily multivitamin or placebo||PHS II16||Long-term multivitamin supplementation||14,641 U.S. physicians||No significant effect observed of daily multi-vitamin on incidence of PCa or cancer-specific mortality|
|Randomization to intensive lifestyle program consisting of vegan diet, vitamin supplementation, aerobic exercise, and stress management and support||Prostate Cancer Lifestyle Trial17||Comprehensive lifestyle modification||93 men with early-stage PCa||In short-term follow-up, experimental group associated with greater PSA declines, inhibition of LNCaP growth by serum|
Considerable heterogeneity exists within empiric lifestyle behavior patterns, while bias in opportunities for detection of PCa also varies with screening practices.4 Nonetheless, correlative evidence from preclinical models supports a potential benefit from dietary modifications, particularly cruciferous vegetables and carotenoids, which appear to confer a protective effect on PCa pathogenesis.5 Similarly, a pilot study of comprehensive lifestyle changes among men with clinical low-risk disease have examined changes in telomere length, a feature of chromosomal stability, where shorter telomere length is associated with aging.6 The intervention group consisted of 10 individuals who underwent dietary modification, aerobic exercise, stress management, and social support. They were compared to a control group. After five years, men in the intervention arm had increased telomere length, whereas men in the control group experienced statistically significant decreases, suggesting the biologic impact of the alterations in lifestyle. Further investigation is warranted to determine whether telomere length and other molecular surrogates can represent a meaningful indicator of clinical disease progression.
Longitudinal follow-up studies have afforded an opportunity to assess the long-term effect of diet and health behaviors on the subsequent outcomes from PCa. The Health Professionals Follow-Up Study (HPFS), a cohort study of male health professionals started in 1986, collects data relating to medical comorbidity, height/weight, physical activity, and smoking status. This study has yielded valuable insights into the factors that affect PCa outcomes. For example, cigarette smoking at the time of diagnosis has been shown to be associated with increased risk of disease-specific mortality, and cardiovascular disease-related and overall mortality, while greater than 10-year periods of smoking cessation were comparable to cancer-specific mortality risks for nonsmokers.7 Furthermore, Richman et al. examined 4,577 men with non-metastatic PCa and found that vegetable fat intake after diagnosis was associated with a lower risk of lethal disease and all-cause mortality, whereas saturated and trans fats after diagnosis were associated with higher all-cause mortality.8
Recently, Kenfield et al. examined the effect of diet and lifestyle on the prevention of lethal PCa within the HPFS cohort. The authors derived a score assigning points corresponding to risk for independent lifestyle factors, including smoking status, body mass index, physical activity, intake of tomatoes and fatty fish, as well as intake level of processed meat (see Table 2).9 Within this framework, increasing lifestyle scores were inversely associated with risk of lethal PCa. For example, those with a score of 5–6 versus 0–1 had a 68 percent lower risk of lethal PCa, whereas men with three dietary factors versus zero had a 46 percent decreased risk. Such information may prove useful in counseling men both before and after disease diagnosis.
Table 2. Definitions of the lifestyle score derived from the HPFS on the occurrence of lethal PCa9
|Smoking status||Never smoker or quit ≥10 years||1|
|Body mass index||<30 kg/m2||1|
|Physical activity||≥3 hours/week vigorous activity (≥6 METs) and/or ≥7 hours/week brisk walking||1|
|Tomatoes||≥7 servings/week raw tomatoes, tomato juice, tomato sauce, salsa, pizza||1|
|Fatty fish||≥1 serving/week mackerel, salmon, sardines, blue-fish, swordfish||1|
|Processed meat||<3 servings/week of beef or pork hot dogs, bacon, salami, bologna, or other processed meat sandwiches, and other processed meats||1|
The Men’s Eating and Living (MEAL) Study (CALGB 70807 [Alliance]), a prospective study evaluating the role of diet on clinical progression among men with PCa managed with active surveillance, recently completed accrual.10,11 This randomized phase III clinical trial is designed to examine whether a two-year intervention consisting of increased vegetable intake would impact PCa progression. The study enrolled 464 men ages 50–80 with recently diagnosed PCa who meet the following inclusion criteria: clinical stage ≤T2a, prostate-specific antigen (PSA) <10 ng/mL, <25 percent biopsy cores positive for cancer, and ≤50 percent of any single core; for men ≤70 years, biopsy Gleason score ≤3+3, and for men older than 70 years, Gleason score ≤3+4. Participants in the intervention group were assigned to a personal counselor and were encouraged to consume at least seven servings of vegetables, two servings of fruit, two servings of whole grains, and one serving of beans or legumes per day, whereas those in the control group received printed materials recommending consumption of a healthy diet. The primary study outcome is clinical progression, which is defined as PSA>10 ng/mL, PSA doubling time <3 years, or increase in tumor volume or Gleason score.12 Results from the study are expected next summer.
The performance of such a trial serves to fill a considerable need to quantify the effect of a well-specified dietary intervention on PCa progression during active surveillance.13 More broadly, MEAL’s completion is notable for representing a randomized trial in low-risk patients, where virtually no level 1 evidence currently exists in support of modifying short-term disease trajectory. These efforts highlight the breadth of work on this topic, ranging from preclinical work addressing putative mechanisms of disease prevention to observational studies, as well as randomized clinical trials that seek to directly examine the effect of discrete dietary and lifestyle interventions.
- Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.
- Klein EA, Thompson IM, Jr., Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556.
- Fortmann SP, Burda BU, Senger CA, et al. Vitamin, Mineral, and Multivitamin Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Report No. 108. AHRQ Publication No. 14-05199-EF-1. Rockville MD: Agency for Healthcare Research and Quality; 2013.
- Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003;12(12):1403-1409.
- Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst. 2002;94(5):391-398.
- Ornish D, Lin J, Chan JM, et al. Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Lancet Oncol. 2013;14(11):1112-1120.
- Kenfield SA, Stampfer MJ, Chan JM, Giovannucci E. Smoking and prostate cancer survival and recurrence. JAMA. 2011;305(24):2548-2555.
- Richman EL, Kenfield SA, Chavarro JE, et al. Fat intake after diagnosis and risk of lethal prostate cancer and all-cause mortality. JAMA Intern Med. 2013;173(14):1318-1326.
- Kenfield SA, Batista JL, Jahn JL, et al. Development and application of a lifestyle score for prevention of lethal prostate cancer. J Natl Cancer Inst. 2016;108(3).
- 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.
- Lippman SM, Klein EA, Goodman PJ, 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):39-51.
- Parsons JK, Pierce JP, Mohler J, et al. A randomized trial of diet in men with early stage prostate cancer on active surveillance: Rationale and design of the Men’s Eating and Living (MEAL) Study (CALGB 70807 [Alliance]). Contemp Clin Trials. 2014;38(2):198-203.
- 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. J Natl Cancer Inst. 1998;90(6):440-446.
- Virtamo J, Pietinen P, Huttunen JK, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: A postintervention follow-up. JAMA. 2003;290(4):476-485.
- Virtamo J, Taylor PR, Kontto J, et al. Effects of alpha-tocopherol and beta-carotene supplementation on cancer incidence and mortality: 18-year postintervention follow-up of the Alpha-tocopherol, Beta-carotene Cancer Prevention Study. Int J Cancer. 2014;135(1):178-185.
- Gaziano JM, Sesso HD, Christen WG, et al. Multivitamins in the prevention of cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2012;308(18):1871-1880.
- Ornish D, Weidner G, Fair WR, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005;174(3):1065-1069; discussion 1069-1070.