|INVITED RESEARCH HIGHLIGHT
|Year : 2015 | Volume
| Issue : 6 | Page : 874-877
Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods
Mark A Moyad
Department of Urology, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
|Date of Web Publication||26-Jun-2015|
Dr. Mark A Moyad
Department of Urology, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109
Source of Support: None, Conflict of Interest: None
Cardiovascular disease (CVD) has been the number one cause of death in the U.S. for 114 of the last 115 years. Risk factors for prostate cancer have primarily mirrored risk proven risk factors for CVD, especially aggressive disease. Obesity, dyslipidemia, glucose intolerance, metabolic syndrome, unhealthy dietary habits or caloric excess, lack of physical activity, and inflammation are just some of these shared risk factors. The evidence also suggests proven CVD preventive measures are identical to prostate cancer preventive measures, especially in regard to aggressive disease. Thus, apart from lifestyle measures that can encourage optimal heart and prostate health there are potentially several dietary supplements that need to be avoided in healthy men because they may also increase the risk of prostate cancer. However, there are also several low-cost, generic, safe in the appropriate individuals, and naturally derived agents that could reduce prostate cancer risk, and these can be discussed and remembered utilizing the acronym S.A.M. (statins, aspirin, and/or metformin).
|How to cite this article:|
Moyad MA. Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods. Asian J Androl 2015;17:874-7
|How to cite this URL:|
Moyad MA. Preventing aggressive prostate cancer with proven cardiovascular disease preventive methods. Asian J Androl [serial online] 2015 [cited 2020 Oct 26];17:874-7. Available from: https://www.ajandrology.com/text.asp?2015/17/6/874/156854 - DOI: 10.4103/1008-682X.156854
This article is based on a presentation delivered on the International Prostate Forum at the Annual Meeting of the American Urological Association, Orlando, Fl, USA, May 18, 2014.
Cardiovascular disease (CVD) has been the number one cause of male death in the U.S. for approximately 114 of the last 115 years, only exceeded for a single year by the influenza pandemic in 1918. ,,, Lifestyle and dietary change for CVD prevention directly appear to apply to cancer prevention and most other prevalent diseases such as type 2 diabetes. Any lifestyle change that mitigates the risk of heart disease has clinical evidence; it could reduce the risk of prostate cancer, especially aggressive disease, and parameters that increase the risk of heart disease increase the risk of aggressive prostate cancer.
| Heart Health Mirrors Prostate Health|| |
The positive or negative behavioral or lifestyle changes associated with CVD and prostate cancer abound. For example, smoking has been associated with a higher risk of being diagnosed with prostate cancer in past meta-analyses,  a higher risk of aggressive prostate cancer, and mortality from prostate cancer. , Obesity is also associated with a higher risk of aggressive and fatal prostate cancer,  and a higher risk of recurrence posttreatment.  It is also plausible that obesity is associated with a lower risk of localized prostate cancer, and a higher risk of advanced disease. , Regular vigorous exercise (approximately 3 h or more per week) is a profound potential strategy to reduce significantly prostate cancer death after diagnosis, and simultaneously reduce all-cause mortality to a similar degree (50%-60%) in these same patients compared to men that perform only 1 h or less exercise per week.  Past studies including a recent summary of 22 studies published over the past 12 years support the modest prostate cancer prevention effects of exercise. ,,
The correlation between prostate cancer risk and hypertension and/or anti-hypertensive medications are currently weak.  However, hypertension as part of a continuum of unhealthy parameters such as observed with metabolic syndrome (central obesity, dyslipidemia and insulin resistance) is becoming a potential risk factor for prostate diseases including cancer.  Alpha-blockers, originally discovered for blood pressure control, are still one of those most effective treatments for men with prostate issues (BPH) and lower urinary tract symptoms (LUTS) despite not having consistent positive or negative impacts on prostate cancer risk. , The synergistic impact of exercise and diet has demonstrated blood pressure lowering effects similar to most anti-hypertensive drug classes.  Caloric reduction in overweight and obese patients with or without hypertension may also provide similar benefits. ,
| Multivitamins/Dietary Supplements|| |
Some of the largest past prospective epidemiologic studies are suggesting a greater rate of aggressive and fatal prostate cancer when consuming more than 1 multivitamin a day, and a potential further increasing risk when other high-dose individual supplements are also utilized (selenium, Vitamin E and zinc).  Men with a family history of prostate cancer appeared to experience the largest and most significant elevated risks of this condition. Other large male observational studies have found somewhat similar results with multivitamins and some individual supplements. ,, Multivitamins are also replete in my experience with higher doses of B-Vitamins such as B12 and folic acid, which have also recently been found to potentially have no impact on health or increase the risk of prostate cancer from the largest and most recent meta-analysis of clinical trials. ,,
Regardless, the only true phase-3 like multivitamin trial for cancer prevention was the Physicians' Health Study 2 (PHS2), which included over 11 000 health male doctors and utilized a low-cost daily single oral multivitamin (Centrum ® Silver). This multivitamin had similar safety to placebo over 11 years, and significantly and modestly reduced the risk of total cancer risk in healthy men (primary endpoint) and cataracts (secondary endpoint). There was no significant reduction in prostate cancer incidence or mortality, but nonsignificant modest reductions were observed. ,, It is also interesting that the original Centrum Silver utilized during this trial from 1997 to 2011 is not the identical product offered to consumers currently because over time these nutritional formulations appear to change based on some science and marketing. Patient could be encouraged to utilize Centrum Silver or something close to the formula, which is detailed in the first clinical trial publication for overall cancer prevention but not prostate cancer prevention in those with and without a baseline history of cancer. 
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was the largest dietary supplement trial ever completed in prostate cancer.  It randomized over 35 000 men into four groups: high-dose Vitamin E (400 IU day−1 ), high-dose selenium (200 mcg day−1 ), Vitamin E and selenium, or placebo. The trial was terminated early after a median of 5.5 years due to a lack of efficacy, although at the time a nonsignificant (P = 0.06) increase risk of prostate cancer in the Vitamin E arm, and type 2 diabetes in the selenium group (P = 0.16) were observed. Still, participant follow-up continued (54 464 added person-years), which provided more clarity of the further health impacts after the cessation of these agents.  A significant (P = 0.008; HR = 1.17) increased risk of prostate cancer was observed in the Vitamin E group, and the increased risk with this individual supplement began to emerge after only 3 years and was found to be consistent for low- and high-grade disease types. The risk of Gleason 7 or higher disease was greater for the three intervention arms compared to placebo but did not reach statistical significance. The HR and P value for Gleason 7 and higher disease compared to placebo were 1.16 (P = 0.20), 1.21 (P = 0.11), and 1.23 (P = 0.08) for Vitamin E, selenium, and the combination, respectively. Additionally, members of the SELECT research team recently reported a significantly increased risk of aggressive prostate cancer in men replete with selenium before utilizing a selenium supplement.  This continues to raise concerns over adding antioxidants in large quantities for healthy individuals already receiving sufficient levels of these compounds (as argued previously) from other sources such as regular dietary intake.
Countless other dietary supplements are replete with their own issues in terms of prostate cancer prevention or treatment. For example, Vitamin D in mega-doses may have some similar issues to Vitamin E or selenium. In the area of prostate cancer prevention, Vitamin D has not been impressive thus far. Several epidemiologic studies have found either no impact or a potentially increased risk of aggressive prostate cancer or total cancer at higher 25-OH Vitamin D blood levels. , For prostate cancer prevention, the Vitamin D test may provide more harm than good until more clinical endpoints are followed in healthy individuals.  The latest Institute of Medicine (IOM) report should also be a reminder that despite the perception, the recommended intakes of Vitamin D have only increased by 200 IU (5 mcg) in most groups and Vitamin D supplements still have the potential to increase the risk of hypercalcemia and nephrolithiasis. 
Vitamin D blood levels may also simply be a marker of healthy behavior.  Higher levels of systemic inflammation and greater burden of many diseases can inhibit Vitamin D synthesis rendering supplementation futile or meaningless in some cases. For example, a lean man, with a low cholesterol level that consumes fish and exercises regularly is more likely to have a higher blood level of Vitamin D compared to a physically inactive overweight or obese man with dyslipidemia and other heart unhealthy parameters. , Patients should be reminded that improvement in heart healthy parameters could increase Vitamin D levels without or with additional smaller increments in supplementation. This moment represents an opportunity to emphasize heart healthy lifestyle changes first before increasing pill counts.
| S.A.M. (Statins, Aspirin and/or Metformin)|| |
Clinicians could discuss countless advertised options for prostate cancer prevention, but since none are currently associated with consistent reduction and the clinical visit needs to be efficient and pithy another approach can be successful with patients. An ancillary pill in prostate cancer should be proven to be heart healthy, cost-effective, benefits need to outweigh the risks, and there should be a minimal chance that this agent interferes with proven conventional treatment. Thus, the list is short but three such interventions exist and arguably should be discussed and also referred to the patient's primary care doctor. The acronym S.A.M. (statins, aspirin, and metformin) should arguably receive the most initial attention (everything else is secondary in my opinion). All three of these agents are "natural" (statins were derived from yeast, aspirin from willow bark, and metformin from the French Lilac), generic, heart healthy, low-cost and if a patient qualifies (benefit outweighs the risk) then there are arguably no other ancillary pills/supplements that have as much overall positive morbidity and mortality data. Some supplements may be able to mimic the activity of these agents and could serve as an alternative for drug intolerant patients (for example, red yeast rice supplements instead of a statin). 
Lower lipid levels have been associated with a lower risk of aggressive prostate cancer,  and increases in HDL ("good cholesterol") may also be protective.  Heart disease may increase the risk of prostate cancer from observations derived from two notable pharmacologic studies of prostate cancer prevention, , and a variety of epidemiologic investigations.  Some of the largest observational studies have suggested a lower risk of aggressive prostate cancer with cholesterol lowering interventions even when controlling for multiple confounding variables. 
Aspirin has been garnering an impressive amount of preliminary data as a potential anti-cancer agent, especially in the area of colorectal cancer prevention. , However, the overall data also suggest a reduced risk of prostate cancer or aggressive disease with this agent. ,,, The ability of aspirin to further reduce prostate cancer-specific mortality in men receiving radiation or surgery has also garnered some preliminary research.  If a benefit appears to be derived from aspirin it appears, as with statins that men with high-risk disease features or a more aggressive molecular profile consuming these products for longer periods of time (5+ years) are the ones most likely to benefit.  Interestingly, the first large meta-analysis and systematic review of 39 studies (20 case-control and 19 cohort) of aspirin and prostate cancer was recently published and concluded with the following: "aspirin use is inversely related to prostate cancer incidence and PCa-specific mortality."  More recently, data from a large pharmacologic prostate cancer prevention trial (REDUCE) have demonstrated a significant reduction in total and high-grade prostate cancer with aspirin use. 
Metformin is also beginning to demonstrate evidence as a cancer prevention or recurrence inhibition agent in those with and without diabetes and is currently in a phase-3 trial in breast cancer patients with survival as the primary endpoint.  A preliminary small phase-2 trial has suggested it may have the potential to slow the progression of even advanced prostate cancer (1000 mg twice a day).  Additionally, a recent clinical trial of patients with prostate cancer on ADT for 6 months utilizing 850 mg twice a day of metformin with a suggested low glycemic diet (caloric restriction) were able to significantly reduce weight gain, BMI, waist circumference, and systolic blood pressure compared to the control group.  Men on metformin were also able to maintain glucose and HgbA1c levels. Metformin is cost-effective, safe, reduces weight gain, diabetes risk, and arguably CVD and perhaps total cancer and prostate cancer risk. , Preliminary laboratory analysis also suggests that it may be synergistic with a variety of standard and nonstandard agents (including statins). ,
| Conclusion|| |
Patients should be encouraged to do whatever is practical and plausible to reduce their risk of CVD to as close to zero as possible. This should provide the greatest potential to not only reduce the risk of prostate cancer, but other disease morbidity and even impact all-cause mortality. Most major behavioral risk factors for CVD morbidity and mortality appear to be correlated with a higher risk of aggressive prostate cancer and/or fatal prostate cancer. The intention of S.A.M. is not to encourage patients to take one or all of these agents. It is to determine whether or not they already qualify for any of these agents based on their CVD risk. If they qualify the potential for a 2-for-1 or ancillary benefit should be emphasized. It is easy to become enamored by high-tech gadgets and costly agents or even costly dietary supplements, but it is the simplistic advice or changes that have profound impacts on CVD risk and it is beginning to appear as if prostate cancer prevention recommendations should emulate this historic example. In other words, "first do no harm."
| Editorial Comment - (by Dr. John W Davis, Department of Urology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA)|| |
At the 2014 International Prostate Forum, two of our four themes included the very early spectrum of PSA screening and detection, specifically: (1) elevated PSA with prior negative biopsy, and (2) prostate cancer with low lethal potential. In both of these circumstances, the urologist's strategy for a patient may often lead to multiple visits for serial PSA trends and additional diagnostic tests. While I will assume that most urologists do not want to take over primary care duties for their patient, these clinical circumstances certainly open the opportunity to compliment and reinforce healthy living habits and primary care strategies. Some urologists have promoted the concept of "Men's Health" initiatives , and rightly point out our specialty's unique access to these opportunities.
For example, the urologist will likely see two types of patients on a regular basis where the true health-related needs lie beyond the PSA number or prostate cancer risk: (1) patients with obesity and other related co-morbidities who are seeking advice for elevated PSA or low-grade prostate cancer, and (2) patients who are interested (in some cases "interested" would be an understatement, i.e., already taking >5 supplements) in using dietary supplements to avoid prostate cancer and other health threats. In the first scenario, the evidence clearly shows that cardiovascular disease morbidity/mortality will outweigh their risk of being diagnosed with prostate cancer or dying of the disease. We must often still offer them the state-of-the-art in detection and treatment advice but always reinforce that long-term success will require a healthy heart. In the second scenario, the challenge is that there is so much information available for patients to read and often be misled into believing. It is possible that an individual patient can research and read more materials than his urologist! Hence, many urologists depend upon Professor Moyad and colleagues with similar expertise to help us find the most evidence-backed conclusions in this field of dietary supplements.
For patients in my practice, I have posed the question related to overall health and prostate cancer prevention: "where should I send you: the gym, the supplement store, or the pharmacy?" From Professor's Moyad's published books,  my takeaway messages have emphasized the answer is "the gym." In this updated review, he reinforces the key evidence for the benefits of daily exercise, and shows where we may be headed in carefully selected daily vitamin use and/or the developing story of "SAM": Statins, Aspirin, and/or Metformin.
| References|| |
Moyad MA. Complementary and Alternative Medicine for Prostate and Urologic Health. New York: Springer Publishing; 2014.
Writing Group Members, Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, et al.
Heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation
2010; 121: e46-215.
Bonow RO, Smaha LA, Smith SC Jr, Mensah GA, Lenfant C. World Heart Day 2002: the international burden of cardiovascular disease: responding to the emerging global epidemic. Circulation
2002; 106: 1602-5.
Eyre H, Kahn R, Robertson RM, Clark NG, Doyle C, et al.
Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. Circulation
2004; 109: 3244-55.
Huncharek M, Haddock KS, Reid R, Kupelnick B. Smoking as a risk factor for prostate cancer: a meta-analysis of 24 prospective cohort studies. Am J Public Health
2010; 100: 693-701.
Zu K, Giovannucci E. Smoking and aggressive prostate cancer: a review of the epidemiologic evidence. Cancer Causes Control
2009; 20: 1799-810.
Kenfield SA, Stampfer MJ, Chan JM, Giovannucci E. Smoking and prostate cancer survival and recurrence. JAMA
2011; 305: 2548-55.
Cao Y, Ma J. Body mass index, prostate cancer-specific mortality, and biochemical recurrence: a systematic review and meta-analysis. Cancer Prev Res (Phila)
2011; 4: 486-501.
Joshu CE, Mondul AM, Menke A, Meinhold C, Han M, et al.
Weight gain is associated with an increased risk of prostate cancer recurrence after prostatectomy in the PSA era. Cancer Prev Res (Phila)
2011; 4: 544-51.
Discacciati A, Orsini N, Wolk A. Body mass index and incidence of localized and advanced prostate cancer - A dose-response meta-analysis of prospective studies. Ann Oncol
2012; 23: 1665-71.
Woodard G, Ahmed S, Podelski V, Hernandez-Boussard T, Presti J Jr, et al
. Effect of Roux-en-Y gastric bypass on testosterone and prostate-specific antigen. Br J Surg
2012; 99: 693-8.
Kenfield SA, Stampfer MJ, Giovannucci E, Chan JM. Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study. J Clin Oncol
2011; 29: 726-32.
Oliveria SA, Lee IM. Is exercise beneficial in the prevention of prostate cancer? Sports Med
1997; 23: 271-8.
Torti DC, Matheson GO. Exercise and prostate cancer. Sports Med
2004; 34: 363-9.
Young-McCaughan S. Potential for prostate cancer prevention through physical activity. World J Urol
2012; 30: 167-79.
Bhaskaran K, Douglas I, Evans S, van Staa T, Smeeth L. Angiotensin receptor blockers and risk of cancer: cohort study among people receiving antihypertensive drugs in UK General Practice Research Database. BMJ
2012; 344: e2697.
De Nunzio C, Aronson W, Freedland SJ, Giovannucci E, Parsons JK. The correlation between metabolic syndrome and prostatic diseases. Eur Urol
2012; 61: 560-70.
Loeb S, Gupta A, Losonczy L, Tosoian J, Walsh PC. Does benign prostatic hyperplasia treatment with alpha-blockers affect prostate cancer risk? Curr Opin Urol
2013; 23: 2-4.
Roehrborn CG. BPH progression: concept and key learning from MTOPS, ALTESS, COMBAT, and ALF-ONE. BJU Int
2008; 101 Suppl 3: 17-21.
Siervo M, Lara J, Chowdhury S, Ashor A, Oggioni C, et al
. Effects of the Dietary Approach to Stop Hypertension (DASH) diet on cardiovascular risk factors: a systematic review and meta-analysis. Br J Nutr
2014. [Epub ahead of print].
Saneei P, Salehi-Abargouei A, Esmaillzadeh A, Azadbakht L. Influence of Dietary Approaches to Stop Hypertension (DASH) diet on blood pressure: a systematic review and meta-analysis on randomized controlled trials. Nutr Metab Cardiovasc Dis
2014; 24: 1253-61.
Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, et al.
Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst
2007; 99: 754-64.
Stevens VL, McCullough ML, Diver WR, Rodriguez C, Jacobs EJ, et al.
Use of multivitamins and prostate cancer mortality in a large cohort of US men. Cancer Causes Control
2005; 16: 643-50.
Neuhouser ML, Barnett MJ, Kristal AR, Ambrosone CB, King IB, et al.
Dietary supplement use and prostate cancer risk in the Carotene and Retinol Efficacy Trial. Cancer Epidemiol Biomarkers Prev
2009; 18: 2202-6.
Leitzmann MF, Stampfer MJ, Wu K, Colditz GA, Willett WC, et al
. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst
2003; 95: 1004-7.
Wien TN, Pike E, Wisløff T, Staff A, Smeland S, et al
. Cancer risk with folic acid supplements: a systematic review and meta-analysis. BMJ Open
2012; 2: e000653.
Clarke R, Halsey J, Lewington S, Lonn E, Armitage J, et al.
Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: meta-analysis of 8 randomized trials involving 37 485 individuals. Arch Intern Med
2010; 170: 1622-31.
Collin SM, Metcalfe C, Refsum H, Lewis SJ, Zuccolo L, et al.
Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev
2010; 19: 1632-42.
Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, et al.
Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA
2012; 308: 1871-80.
Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, et al.
Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA
2012; 308: 1751-60.
Christen WG, Glynn RJ, Manson JE, MacFadyen J, Bubes V, et al.
Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology
2014; 121: 525-34.
Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, 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: 39-51.
Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, et al.
Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA
2011; 306: 1549-56.
Kristal AR, Darke AK, Morris JS, Tangen CM, Goodman PJ, et al.
Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk. J Natl Cancer Inst
2014; 106: djt456.
Barnett CM, Nielson CM, Shannon J, Chan JM, Shikany JM, et al.
Serum 25-OH vitamin D levels and risk of developing prostate cancer in older men. Cancer Causes Control
2010; 21: 1297-303.
Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med
2011; 155: 827-38.
Isenor JE, Ensom MH. Is there a role for therapeutic drug monitoring of vitamin D level as a surrogate marker for fracture risk? Pharmacotherapy
2010; 30: 254-64.
Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Institute of Medicine of the National Academies. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011.
Ardawi MS, Sibiany AM, Bakhsh TM, Qari MH, Maimani AA. High prevalence of vitamin D deficiency among healthy Saudi Arabian men: relationship to bone mineral density, parathyroid hormone, bone turnover markers, and lifestyle factors. Osteoporos Int
2012; 23: 675-86.
Jääskeläinen T, Knekt P, Marniemi J, Sares-Jäske L, Männistö S, et al.
Vitamin D status is associated with sociodemographic factors, lifestyle and metabolic health. Eur J Nutr
2013; 52: 513-25.
Kotani K, Sekine Y, Ishikawa S, Ikpot IZ, Suzuki K, et al
. High-density lipoprotein and prostate cancer: an overview. J Epidemiol
2013; 23: 313-9.
Platz EA, Till C, Goodman PJ, Parnes HL, Figg WD, et al.
Men with low serum cholesterol have a lower risk of high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev
2009; 18: 2807-13.
Thomas JA 2 nd
, Gerber L, Bañez LL, Moreira DM, Rittmaster RS, et al.
Prostate cancer risk in men with baseline history of coronary artery disease: results from the REDUCE Study. Cancer Epidemiol Biomarkers Prev
2012; 21: 576-81.
Murtola TJ, Visakorpi T, Lahtela J, Syvälä H, Tammela TLj. Statins and prostate cancer prevention: where we are now, and future directions. Nat Clin Pract Urol
2008; 5: 376-87.
Crosara Teixeira M, Braghiroli MI, Sabbaga J, Hoff PM. Primary prevention of colorectal cancer: myth or reality? World J Gastroenterol
2014; 20: 15060-9.
Sostres C, Gargallo CJ, Lanas A. Aspirin, cyclooxygenase inhibition and colorectal cancer. World J Gastrointest Pharmacol Ther
2014; 5: 40-9.
Shebl FM, Sakoda LC, Black A, Koshiol J, Andriole GL, et al.
Aspirin but not ibuprofen use is associated with reduced risk of prostate cancer: a PLCO study. Br J Cancer
2012; 107: 207-14.
Bosetti C, Rosato V, Gallus S, Cuzick J, La Vecchia C. Aspirin and cancer risk: a quantitative review to 2011. Ann Oncol
2012; 23: 1403-15.
Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, et al
. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet
2011; 377: 31-41.
Mahmud S, Franco E, Aprikian A. Prostate cancer and use of nonsteroidal anti-inflammatory drugs: systematic review and meta-analysis. Br J Cancer
2004; 90: 93-9.
Choe KS, Cowan JE, Chan JM, Carroll PR, D'Amico AV, et al
. Aspirin use and the risk of prostate cancer mortality in men treated with prostatectomy or radiotherapy. J Clin Oncol
2012; 30: 3540-5.
Jacobs EJ, Newton CC, Stevens VL, Campbell PT, Freedland SJ, et al
. Daily aspirin use and prostate cancer-specific mortality in a large cohort of men with nonmetastatic prostate cancer. J Clin Oncol
2014; 32: 3716-22.
Bosetti C, Rosato V, Gallus S, La Vecchia C. Aspirin and prostate cancer prevention. Recent Results Cancer Res
2014; 202: 93-100.
Vidal AC, Howard LE, Moreira DM, Castro-Santamaria R, Andriole GL, et al
. Aspirin, NSAIDs, and risk of prostate cancer: results from the REDUCE study. Clin Cancer Res
2015; 21: 756-62.
Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AK, et al.
Metformin: taking away the candy for cancer? Eur J Cancer
2010; 46: 2369-80.
Rothermundt C, Hayoz S, Templeton AJ, Winterhalder R, Strebel RT, et al.
Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09). Eur Urol
2014; 66: 468-74.
Nobes JP, Langley SE, Klopper T, Russell-Jones D, Laing RW. A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy. BJU Int
2012; 109: 1495-502.
Clements A, Gao B, Yeap SH, Wong MK, Ali SS, et al
. Metformin in prostate cancer: two for the price of one. Ann Oncol
2011; 22: 2556-60.
Colquhoun AJ, Venier NA, Vandersluis AD, Besla R, Sugar LM, et al.
Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer. Prostate Cancer Prostatic Dis
2012; 15: 346-52.
Babcook MA, Sramkoski RM, Fujioka H, Daneshgari F, Almasan A, et al.
Combination simvastatin and metformin induces G1-phase cell cycle arrest and Ripk1- and Ripk3-dependent necrosis in C4-2B osseous metastatic castration-resistant prostate cancer cells. Cell Death Dis
2014; 5: e1536.
Kirby RS, Kirby M. The urologist as an advocate of men's health: 10 suggested steps toward helping patients achieve better overall health. Urology
2005; 66 5 Suppl: 52-6.
Goldenberg SL, White A. Male health-a recent paradigm. Nat Rev Urol
2015; 12: 15-16.
Moyad MA. Promoting Wellness: for Prostate Cancer Patients. 4 th
ed. Ann Arbor, MI: Spry Publishing LLC; 2013.
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