Can You Prevent Prostate Cancer? - 025
Risk factors for prostate cancer
Before examining if you can prevent prostate cancer, you must know its risk factors:
Age
Race
Family history and genetics
Age
Nearly 60% of all prostate cancers occur in men over age 65.1
Incidence of prostate cancer by age:
1 in 456 men under the age of 50
1 in 54 men ages 50 to 59
1 in 19 men ages 60 to 69
1 in 11 men ages 70 and older
Adding to the many quirks of prostate cancer is that it is increasing worldwide among older adolescents and young adults. The incidence among men ages 15 to 40 has risen steadily globally, averaging a 2% rise yearly since 1990. Men diagnosed under age 40 have a higher risk for metastases and death than older men.2
Race
Prostate cancer is more common in men with African ancestry than Caucasians and Asian Americans. African American men tend to have an earlier disease onset and are more than twice as likely to die from it. 3
Family history and genetics
Prostate cancer is one of the most inheritable cancers. Twin studies estimate that genetic factors drive 58% of the variation in risk. Men with a brother or father with prostate cancer have two to four times the risk of being diagnosed with prostate cancer, with a higher risk if a brother has prostate cancer. And men with a family history of breast cancer have a 21% greater risk of prostate cancer.4
Heritable factors contributing to the risk of prostate cancer include rare germline mutations such as BReast CAncer Gene 2 (BRCA2) and ataxia telangiectasia mutated (ATM). More common heritable gene variants that may influence prostate cancer risk are single nucleotide polymorphisms (SNPs). A SNP is a variation in a single base position in a DNA sequence. I discussed these heritable mutations in newsletter 16.
Modifiable risk factors
Some genetic risk factors are modifiable. Heritable mutations such as SNPs may create susceptibility to prostate cancer but don't mean you'll be diagnosed with it.
One group of researchers set out to see if you could reduce the potential increased risk of prostate cancer associated with SNPs. They designed a study to see if men at an increased genetic risk of prostate cancer can offset their risk of disease or disease progression by adhering to a healthy lifestyle.5
The researchers defined a healthy lifestyle as a healthy weight, vigorous physical activity, not smoking, and a healthy diet.
This study prospectively followed 12,411 men in the Health Professionals Follow-up Study (1993–2019) and the Physicians' Health Study (1983–2010). They checked each man for 269 single nucleotide polymorphisms (SNPs) associated with a higher risk for prostate cancer.
The higher the number of variants, the higher their polygenic risk score and the higher the men's risk for prostate cancer. The lifetime risk of prostate cancer is >50% among men in the highest 10% of polygenic risk scores and <10% among men in the lowest 10%.
It found that among men with a high genetic risk for prostate cancer, those adhering to a healthy lifestyle had a 45% reduction in the risk of lethal prostate cancer compared with those not following a healthy lifestyle.
Unfortunately, the study did not find a reduction in overall prostate cancer risk by following a healthy lifestyle. But the researchers did conclude,
"Maintaining a healthy lifestyle may provide a way to offset the genetic risk of lethal prostate cancer."
Another recent study examined combining a predominantly plant-based diet with exercise to lower the risk of prostate cancer progressing or recurring. They analyzed 2,038 men diagnosed with prostate cancer at stages T1, T2, or T3a with a median age of 64.6
Stages T1 and T2 mean the tumor remains confined within the prostate. Stage T3 means the cancer has broken through the capsule but remains localized.
Men in the highest 20% who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood) had a 52% lower risk of progression and a 53% lower risk of prostate cancer recurrence.
Men who consumed a predominantly plant-based diet in the highest 20% and exercised daily by walking at a fast pace more than three times a week had a 59% lower risk of prostate cancer recurrence.
A significant finding was that the grade and stage of cancer did not modify associations between either index and prostate cancer progression or recurrence. In other words, some men with locally advanced prostate cancer, stage T3, also showed these positive associations.
Studies on diet and prostate cancer risk are observational and not definitive. In addition, there are multiple studies looking at how various types of diets and individual nutrients affect the incidence of prostate cancer. I chose not to review those in this newsletter because the results are not definitive and sometimes conflicted.
Data suggests that maintaining a healthy weight, vigorous physical activity, not smoking, and following a healthy diet reduce prostate cancer progression, recurrence, and lethality.
Despite the lack of evidence for dietary prevention of prostate cancer, there is substantial evidence of using pharmaceutical drugs to prevent prostate cancer. Two randomized trials evaluated the drugs finasteride and dutasteride to prevent prostate cancer.
Finasteride (Proscar) and dutasteride (Avodart) treat the symptoms of benign prostatic hyperplasia, an enlarged prostate. They are 5-alpha reductase inhibitors that block the enzyme converting testosterone to the more potent androgen, dihydrotestosterone (DHT).
The long-term benefit of these drugs is to shrink the prostate, thus improving symptoms of an enlarged prostate. Chronic therapy with dutasteride reduces serum DHT by 93% and finasteride by 70%.7
Since testosterone and dihydrotestosterone are the main drivers of normal and cancerous prostate cell growth, researchers theorized that by blocking the conversion to the more potent hormone, these drugs could prevent the development of prostate cancer. In addition, men born with an inherited deficiency of 5-alpha reductase do not develop prostate cancer.
Prostate Cancer Prevention Trial
The Prostate Cancer Prevention Trial (PCPT) was a randomized, double-blind, placebo-controlled study designed to determine whether finasteride could prevent prostate cancer.8 Half of the men in the study took finasteride 5mg, and the other half took a placebo.
The PCPT enrolled 18,882 men ages 55 and older and began in October 1993 at 221 sites across the United States. It was expected to continue until May 2004 but stopped in June 2003 when it showed that finasteride reduced the risk of developing prostate cancer by 25%.
Additional analyses in 2013 showed that finasteride reduced the risk of developing prostate cancer by about 30%.9
Initially, there was concern about an increased risk of developing high-grade prostate cancer in some men who took finasteride. But after further analysis of the data, the slight increase in high-grade disease among men in the finasteride arm (333 of 9,423 or 3.5 percent ) versus men in the placebo arm (286 of 9,457 or 3 percent) was not statistically significant.10
Reduction by Dutasteride of Prostate Cancer Events
Another study examined dutasteride's effect on prostate cancer incidence among men at increased risk for the disease. The "Reduction by Dutasteride of Prostate Cancer Events" (REDUCE) trial was a four-year randomized, double-blind, placebo-controlled study involving men randomly assigned dutasteride 0.5 mg daily or placebo.11
Men were enrolled in the trial if they were ages 55 - 75, had a prostate-specific antigen (PSA) level of 2.5 ng to 10 ng per milliliter, and had one negative prostate biopsy within six months of enrollment. They underwent another prostate biopsy in years 2 and 4 of the study.
During the four years of the study, 659 of the 3305 men in the dutasteride group (19.9%) and 858 of the 3424 men in the placebo group (25.1%) received a diagnosis of prostate cancer. Dutasteride was associated with a relative risk reduction of 23%.
Relative risk reduction tells you by how much dutasteride reduced the risk of prostate cancer relative to the control group of men who took a placebo.
This study showed dutasteride reduced the incidence of prostate cancer in men at high risk for the disease, but this reduction was mainly limited to tumors with a Gleason score of 5 or 6. There was no statistically significant reduction in intermediate and high-grade tumors with Gleason scores of 7 to 10 when comparing dutasteride to placebo.
Despite both groups showing similar numbers of tumors with Gleason scores of 8 to 10 in the first two years, a troubling discrepancy emerged. During years three and four, the dutasteride group had twelve tumors with Gleason scores of 8 to 10, and the placebo group only had one.
A review published in October 2014 looked at potential biases in these trials, which may have accounted for some of the discrepancies, and concluded:
"Numerous mathematical models reflect with confidence that 5α-RIs (5-alpha reductase inhibitors) are not likely to increase risk for high-grade prostate cancer, and significantly enough others predict an actual reduced risk for all grades of prostate cancer by these agents. Furthermore, follow-up data from the REDUCE trial following an additional 2 years showed no new Gleason 8–10 tumors."12
The answer
So the answer to the original question proposed is yes, you can prevent prostate cancer with 5-alpha reductase inhibitors finasteride and dutasteride.
Despite further analysis showing that neither drug increases the risk for high-grade prostate cancer, the Food and Drug Administration declined to approve either drug to prevent prostate cancer. Reasons for that might include no increase in overall survival and the REDUCE trial only preventing low-grade Gleason tumors.
It would be interesting to see a randomized, double-blind, placebo-controlled trial examining whether 5-alpha reductase inhibitors prevent prostate cancer in men with high-risk SNPS, resulting in high polygenic risk scores.
Even though clinical trials involving a healthy lifestyle didn't show prostate cancer prevention, they clearly showed reduced progression, recurrence, and lethality once it occurred.
Based on the research the Prostate Cancer Foundation has reviewed, they provide ten considerations for preventing prostate cancer, so I'll close with a link to them.
Until next time, stay healthy.
Much love,
Keith
"Prostate Cancer Survival Rates | Prostate Cancer Foundation." Prostate Cancer Foundation, https://www.facebook.com/PCF.org, https://www.pcf.org/about-prostate-cancer/what-is-prostate-cancer/prostate-cancer-survival-rates/. Accessed 1 Aug. 2023.
Bleyer, Archie, et al. "Prostate Cancer in Young Men: An Emerging Young Adult and Older Adolescent Challenge." Cancer, no. 1, Wiley, Sept. 2019, pp. 46–57. Crossref, doi:10.1002/cncr.32498.
Parker, Patrick M., et al. "Prostate Cancer in Men Less Than the Age of 50: A Comparison of Race and Outcomes." Urology, no. 1, Elsevier BV, July 2011, pp. 110–15. Crossref, doi:10.1016/j.urology.2010.12.046.
Barber, Lauren, et al. "Family History of Breast or Prostate Cancer and Prostate Cancer Risk." Clinical Cancer Research, no. 23, American Association for Cancer Research (AACR), Dec. 2018, pp. 5910–17. Crossref, doi:10.1158/1078-0432.ccr-18-0370.
Plym, Anna, et al. "A Healthy Lifestyle in Men at Increased Genetic Risk for Prostate Cancer." European Urology, no. 4, Elsevier BV, Apr. 2023, pp. 343–51. Crossref, doi:10.1016/j.eururo.2022.05.008.
Liu, Vivian N., et al. "Associations between Plant-Based Diets and Risk of Disease Progression in Men with Prostate Cancer." Journal of Clinical Oncology, no. 6_suppl, American Society of Clinical Oncology (ASCO), Feb. 2023, pp. 392–392. Crossref, doi:10.1200/jco.2023.41.6_suppl.392.
Nickel JC. Comparison of clinical trials with finasteride and dutasteride. Rev Urol. 2004;6 Suppl 9(Suppl 9):S31-39.
Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215-224.
Thompson IM, Goodman PJ, Tangen CM, et al. Long-term survival of participants in the prostate cancer prevention trial. N Engl J Med. 2013;369(7):603-610.
"Prostate Cancer Prevention Trial (PCPT): Questions and Answers - NCI." National Cancer Institute, https://www.cancer.gov/types/prostate/research/prostate-cancer-prevention-trial-qa. Accessed 28 July 2023.
Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362(13):1192-1202.
Lacy JM, Kyprianou N. A tale of two trials: The impact of 5α-reductase inhibition on prostate cancer (Review). Oncology Letters. 2014;8(4):1391-1396.