(UroToday.com) The 2022 American Urological Association (AUA) Annual Meeting included the International Prostate Forum session and a presentation by Dr. Justin Gregg discussing the impact of diet, exercise and supplements on prostate cancer prevention and early disease non-progression. Dr. Gregg noted that the primary objective of his presentation was to describe the current evidence for modifiable risk factors associated with prostate cancer development and disease progression, specifically discussing prostate cancer risk, progression on active surveillance, and advanced disease progression.
With regards to prostate cancer risk, Dr. Gregg highlighted that the 2018 version of ‘Diet, nutrition, physical activity and prostate cancer’ published by the World Cancer Research Fund and the American Institute for Cancer Research provides several important insights. For assessing increased risk of “aggressive” disease, this is probably related to body fat and adult height, whereas there is limited evidence for dairy (high calcium diet), low alpha-tocopherol, and low plasma selenium. Dr. Gregg suggests that 34% of patients start with at least one risk factor for prostate cancer, commonly metabolic syndrome. A previous meta-analysis of 24 cohort studies from Gacci et al.1 suggests that metabolic syndrome is associated with an OR of 1.17 (95% CI 1.00-1.36) for any prostate cancer, and an OR of 1.89 (95% CI 1.50-2.38) for Gleason Group 4 or higher disease. Data for physical activity and risk of prostate cancer are surprisingly lacking in this area, with a previous meta-analysis suggesting no increased risk of Gleason Group >=2 disease (RR 0.92, 95% CI 0.80-1.06). Data on diet suggests that increased dairy intake, decreased fish intake, and decreased lycopene/tomato intake is possibly related to increased risk of cancer.
The use of statins has been a hot topic with regards to risk of prostate cancer risk. In a comprehensive review from Alfaqih et al.,2 they highlighted that among >30 observational studies on statin use and prostate cancer risk published to date, most support the hypothesis that statin use reduces the risk of advanced prostate cancer. Furthermore, statin use also seems to be associated with improved prostate-cancer-specific survival, particularly in men undergoing radiotherapy, suggesting a role for statins in secondary and tertiary prostate cancer prevention. As follows is a summary figure highlighting statin use, high cholesterol, and prostate cancer deaths in the United States:
Dr. Gregg emphasized that there are potentially other modifiable risk factors with regards to prostate cancer risk (not discussed in this talk), including prevention using 5-alpha reductase inhibitors, smoking, and ejaculatory frequency.
Dr. Gregg then discussed prostate cancer progression, highlighting a study from Zuniga and colleagues that looked at diet and lifestyle considerations for patients with prostate cancer.3 This study focused on randomized clinical trials with supplemented data from observational studies. Dr. Gregg notes that from this study there is evidence to suggest that lycopene/tomatoes have data to suggest a benefit for localized prostate cancer, as well as advanced prostate cancer. For green tea, there is also data to suggest a possible benefit for localized prostate cancer, but no data for advanced disease.
The MEAL randomized clinical trial, published in 20204 was a phase 3 randomized clinical trial testing high vegetable intake with patients randomized to telephone counseling versus receiving written information about diet and prostate cancer. Outcomes included time to progression (PSA, PSA doubling time, grade). Among 478 men randomized, there were 245 progression events (intervention arm: 124; control arm: 121), with no significant differences in time to progression (unadjusted HR 0.96, 95% CI 0.75 to 1.24; adjusted HR 0.97, 95% CI 0.76 to 1.25). The 24-month Kaplan-Meier progression-free percentages were 43.5% [95% CI, 36.5% to 50.6%] and 41.4% [95% CI, 34.3% to 48.7%] for the intervention and control groups, respectively (difference, 2.1% [95% CI, -8.1% to 12.2%]):
Dr. Gregg and colleagues also prospectively assessed adherence to the Mediterranean diet with Gleason score progression among 410 men with newly diagnosed prostate cancer on an active surveillance protocol.5 After adjustments for clinical factors, higher adherence to the Mediterranean diet was associated with a lower risk of Grade Group progression among all men (HR per 1-unit increase in Mediterranean diet score, 0.88; 95% CI 0.77-1.01), non-White men (HR per 1-unit increase in Mediterranean diet score, 0.64; 95% CI 0.45-0.92), and men without diabetes (HR per 1-unit increase in Mediterranean diet score, 0.82; 95% CI 0.71-0.96).
The ERASE trial, published in 2021, sought to examine the effects of exercise on cardiorespiratory fitness and biochemical progression in men with prostate cancer who were undergoing active surveillance. There were 52 patients that were randomized to either the high-intensity interval training (HIIT) group or usual care group. The primary outcome of peak V̇o2 increased by 0.9 mL/kg/min in the HIIT group and decreased by 0.5 mL/kg/min in the usual care group (adjusted between-group mean difference 1.6 mL/kg/min; 95% CI, 0.3-2.9; p = 0.01). Additionally, compared with the usual care group, the HIIT group experienced decreased PSA level (-1.1 μg/L; 95% CI, -2.1 to 0.0; p = 0.04) and PSA velocity (-1.3 μg /L/y; 95% CI, -2.5 to -0.1; p = 0.04).
Finally, Dr. Gregg discussed lifestyle effect on advanced prostate cancer progression. Historical data suggests that the use of statins in this population decreases the risk of mortality by ~17%-24%. In 2021, Hamilton et al. [7] performed a secondary analysis of a randomized clinical trial among men undergoing radiation with a PSA > 3 ng/mL who were randomized to intermittent versus continuous ADT (n = 1,364). This analysis suggested that statin use was associated with improved overall survival (HR 0.64, 95% CI 0.53-0.78) and improved prostate cancer specific survival (HR 0.65, 95% CI 0.48-0.87):
In advanced prostate cancer, there may also be an obesity paradox, whereby obesity may be protective, improving overall survival in men with mHSPC, nmCRPC, and mCRPC:
Dr. Gregg concluded his presentation discussing the impact of diet, exercise and supplements on prostate cancer prevention and early disease non-progression with the following take-home messages:
- Risk of prostate cancer is likely related to obesity, physical activity, and diet
- Risk of active surveillance progression may be related to diet and exercise
- Risk of advanced disease progression is likely related to statins, with obesity having a protective mechanism
Presented by: Justin Gregg, MD, University of Texas, MD Anderson Cancer Center, Houston, TX
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.
References:
- Gacci M, Russon GI, De Nunzio C, et al. Meta-analysis of metabolic syndrome and prostate cancer. Prostate Cancer Prostatic Dis. 2017 Jun;20(2):146-155.
- Alfaqih MA, Allott EH, Hamilton RJ, et al. The current evidence of statin use and prostate cancer prevention: Are we there yet? Nat Rev Urol. 2017 Feb;14(2):107-119.
- Zuniga KB, Chan JM, Ryan CJ, et al. Diet and lifestyle considerations for patients with prostate cancer. Urol Oncol. 2020;38:105-117.
- Parsons JK, Zahrieh D, Mohler JL, et al. Effect of a behavioral intervention to increase vegetable consumption on cancer progression among men with early-stage prostate cancer: The MEAL randomized clinical trial. JAMA 2020.
- Gregg JR, Zhang X, Chapin BF, et al. Adherence to the Mediterranean diet and grade group progression in localized prostate cancer: An active surveillance cohort. Cancer. 2021 Mar 1;127(5):720-728.
- Kang DW, Fairey AS, Boule NG, et al. Effects of Exercise on Cardiorespiratory Fitness and Biochemical progression in men with localized prostate cancer under active sureveillance: The ERASE Randomized Clinical Trail. JAMA Oncology. 2021 Oct 1;7(10):1487-1495.
- Hamilton RJ, Ding K, Crook JM, et al. The association between statin use and outcomes in patients initiating androgen deprivation therapy. Eur Urol. 2021.