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Review

SIU-ICUD: Prevention of Lethal Prostate Cancer via Modifiable Heart-Healthy Lifestyle Changes, Metrics, and Repurposed Medications

by
Mark A. Moyad
1,*,
Raj V. Tiwari
2,
Daniel A. Galvão
3,
Dennis R. Taaffe
3 and
Robert U. Newton
3
1
Department of Urology, University of Michigan Medical Center, Ann Arbor, MI 48104, USA
2
Department of Urology, Sengkang General Hospital, Singapore 544886, Singapore
3
Exercise Medicine Research Institute, Edith Cowan University, Perth, WA 6027, Australia
*
Author to whom correspondence should be addressed.
Soc. Int. Urol. J. 2025, 6(3), 40; https://doi.org/10.3390/siuj6030040
Submission received: 24 December 2024 / Revised: 10 February 2025 / Accepted: 14 February 2025 / Published: 7 June 2025
Versions Notes

Abstract

Background/Objectives: Primary prevention, germline, familial, or other pre- or post-diagnostic and standard treatment-elevated progression or recurrence risk and mitigating adverse events from systemic treatment are all clinical opportunities to reduce the risk of lethal prostate cancer. This review attempted to provide a practical and realistic consensus via an international committee of experts who, in general, harbor career-long experience in this discipline. Methods: A PubMed review primarily utilizing the latest meta-analyses, systematic reviews, and methodologically robust epidemiologic recent data adjusting for multiple confounding variables was conducted. The goal of this committee was to highlight tangible options for clinicians and patients. Results: Behavioral patterns and metrics known to reduce cardiovascular morbidity, mortality, and all-cause mortality (premature death) appear to prevent numerous lethal common cancers, including prostate cancer. This practical approach allows for the greatest probability of patient success since cardiovascular disease (CVD) is the primary cause of death in men with and without prostate cancer, and a notable source of morbidity and mortality in men with advanced disease due to systemic conventional treatment as well as the inflammatory contribution of cancer itself. Heart-healthy dietary patterns, exercise, healthy weight/waist circumference, eliminating tobacco, minimizing alcohol exposure, and other behaviors to reduce the risk of CVD should be prioritized. CVD-preventive medications, including aspirin, GLP-1 agonists, metformin, statins, etc., should receive attention to improve compliance for those that already qualify for these agents and to increase the probability of enhancing the quality and quantity of life. Dietary supplements do not have favorable data currently to espouse their utilization to prevent lethal prostate cancer but may have an ancillary role in mitigating some adverse effects of treatment. Conclusions: Remarkably, heart-healthy lifestyle changes, metrics, and promising repurposed medications known to reduce cardiovascular events, promote longevity, and improve mental health could simultaneously prevent lethal prostate cancer. This serendipitous association provides clinicians and their patients a higher probability of success, regardless of their prostate cancer pathway or circumstance.

1. Introduction and Conclusion of the Committee

Proven modifiable heart-healthy behavioral patterns and metrics simultaneously appear to have the most profound impact on reducing the risk of lethal prostate cancer and other common causes of premature death (all-cause mortality) [1,2,3,4,5]. This is a consistent serendipitous message via meta-analyses, systematic reviews, and preliminary clinical or epidemiologic data, as well as from this committee. This is a notable and remarkable opportunity to favorably impact countless current and future patients for a plethora of objective reasons. Cardiovascular disease (CVD) is the primary cause of mortality in men, and the primary cause of death in men diagnosed with and/or treated for localized prostate cancer [6,7,8]. CVD is a common cause of mortality in men with advanced prostate cancer [9]. CVD is one of the primary serious (grade 3 or greater) adverse effects of conventional systemic treatment for men being treated for advanced prostate cancer, which in some cases can disrupt treatment protocols and harbor life-threatening consequences [10]. The inflammatory contribution of progressive cancer itself can also add to the cardiovascular burden [11]. Thus, in the primary prevention setting and throughout all stages of prostate cancer and treatment, CVD prevention should be highlighted, and aggressive measures to reduce CVD risk should be prioritized. The attractiveness of this approach, again, cannot be overstated since the implementation of this CVD-preventive approach to impact lethal prostate cancer and adverse effects of conventional treatment serves to improve all-cause morbidity and mortality, and could improve mental health. Perhaps this concerted motivational two- or three-for-one approach could also assist by improving the current anemic adherence rates of these and other lifestyle changes and metrics [6].

2. Materials and Methods

A committee of global experts with decades of expertise in this specific area of prostate cancer was assembled. This included clinical and research experts having and continuing to be employed in the discipline of lifestyle changes and prostate cancer. A PubMed review primarily utilizing meta-analyses, systematic reviews, and methodologically robust epidemiologic recent data adjusting for multiple confounding variables was conducted. The goal of committee 4 from the 3rd World Urologic Oncology Federation (WUOF)/Société International d’Urologie (SIU) International Consultation on Urological Diseases (ICUD) on localized prostate cancer was to highlight tangible heart-healthy lifestyle-, medication-, and metric-based options for clinicians and patients. Heart healthy in this manuscript is defined as lifestyle changes (diet, exercise, etc.), parameters (blood pressure, cholesterol, glucose, weight/waist, etc.), or medications recommended within cardiovascular guidelines to improve patient outcomes [1,2,6].

3. Results

3.1. Exercise, Physical Activity, Cardiovascular Health, and Lethal Prostate Cancer

The wealth of epidemiologic and clinical evidence for exercise (including physical activity) to prevent CVD and premature morbidity and mortality has been well accepted [6]. Preliminary meta-analyses also suggest a 25–31% reduction in advanced, aggressive, or lethal prostate cancer via greater volume and intensity of exercise [12]. Multiple mechanisms have been proffered from pre-clinical and clinical studies, including beneficial myokine and adipokine profiles, hormone receptor adaptation, enhanced perfusion with a reduction in intra-tumor hypoxia, improved immune function, and reduced systemic inflammation and oxidative stress [13,14,15,16,17,18]. No single mechanism can be credited from laboratory and clinical research; thus, multiple pathways, or pleiotropism, appear to be the consistent theme. Regardless, physical activity or exercise guidelines are profoundly recommended for a variety of benefits. For example, the most recent example from the ERASE trial mirrors these advantages and the philosophy of this committee. This was a 12-week randomized clinical trial of active surveillance (AS) patients, which observed the potential of a regular high-intensity exercise regimen to exhibit anti-cancer activity over a brief duration (reduced prostate specific antigen (PSA), PSA velocity, and LNCaP cell growth), and significantly improved cardiorespiratory fitness and multiple mental health metrics [19,20]. Exercise During Active Surveillance for Prostate Cancer (ERASE) was arguably the first rigorous randomized trial conducted of a supervised high-intensity interval training (HIIT) protocol (treadmill thrice weekly) versus a usual-care control group, which utilized a cardiovascular and respiratory metric (peak oxygen consumption) as a primary outcome to then subsequently determine the potential impact on prostate cancer parameters (secondary outcomes).

3.2. Dietary Patterns (Not a Specific Diet) and Lethal Prostate Cancer

Overall dietary patterns have preliminary evidence to impact progression and mortality. The essence of the dietary pattern that can reduce CVD and improve all-cause mortality also reflects what could generally provide some protection against lethal prostate cancer [21,22]. This is primarily a plant-based or plant-centric, but not exclusively, as of now, a plant-only pattern that includes a greater intake of vegetables, fruits, fish, legumes, and whole grains while minimizing processed foods, red meats, higher-fat dairy, refined grains, sodium-replete products/snacks, and sugar-sweetened beverages. The term “dietary pattern” implies flexibility and discourages myopic messages of micro-dissecting every calorie for quality and quantity. The committee espouses individualized dietary patterns ideally resulting in salubrious cardiovascular metric changes (blood pressure, cholesterol, glucose, weight/waist circumference, etc.) as a primary indicator, along with improved mental health, of the benefit or lack thereof of this lifestyle change.

3.3. Alcohol Minimization/Elimination and Tobacco Cessation

The carcinogenic potential of alcohol is currently well accepted [23]. Still, the focus on higher or heavy intakes and higher risks of aggressive or lethal prostate cancer continues to accumulate evidence. The Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) prostate cancer prevention trials both observed an elevated risk of high-grade cancer among men with greater intakes of alcohol consumption, and the simultaneous potential for the nullification of potential preventive medications [24,25]. Meta-analyses suggest an increased risk of fatal prostate cancer (SRE = 1.33), but inconsistences in some studies were observed [26]. Similarly, an overall increased risk of lethal prostate cancer has been observed for tobacco exposure [27]. Despite multiple proffered mutual mechanisms (carcinogens, inflammation, DNA strand injury and repair inhibition, immune suppression, etc.) for alcohol or tobacco, it is also plausible that the higher risk could also be attributed to a reduced compliance with screening inherent in these unhealthy behavioral patterns.

3.4. Obesity and Cumulative Metabolic Health Parameters (Metabolic Syndrome)

Cumulative data continue to suggest obesity or an unhealthy weight status, regardless of the measurement utilized, is a risk factor for recurrence, advanced, and fatal prostate cancer despite also being associated with a significantly lower risk (−5%) of overall incidence [28,29,30]. Multiple mechanisms have been procured from inflammation, other CVD impetus, hormonal alterations, etc. The profound reduction in testosterone and subsequentially PSA or even hemodilution with obesity could be associated with a reduction in overall incidence. However, it is also plausible that androgen insensitivity could occur over the long term with obesity and hypogonadism, which would then increase the risk of advanced, aggressive, or lethal prostate cancer.

3.5. Heritability of Prostate Cancer, Lifestyle Behaviors, Metric Lessons, and Cardiovascular Health

Cumulative heart-healthy lifestyle changes have preliminary epidemiologic evidence of reducing the risk of aggressive or lethal prostate cancer in men at higher hereditary risk by almost 50% (HR = 0.55) [31]. These are similar behavioral changes recommended by this committee. This is a novel observation, which should be communicated to patients. Germline and familial risk are an increasing area of interest, and prostate cancer continues to be one of the most heritable of all the common cancers in notable twin cohort studies (57% of cases), only surpassed by melanoma (58%) [32]. Heritability of other common tumor types, such as non-melanoma skin (43%), kidney (38%), breast (31%), uterine (27%), or even overall cancer (33%), are also noteworthy, but again are less heritable compared to prostate cancer. This could serve as a surprising but teachable moment for some clinicians and their patients.

3.6. Dietary Supplements and Prostate Cancer

No robust clinical evidence currently exists for a single or combination nutrient dietary supplement to reduce the risk of lethal prostate cancer. However, Selenium and Vitamin E Cancer Prevention Trial (SELECT), the largest randomized trial ever conducted to prevent prostate cancer utilizing supplements, found a concerning significantly higher risk with high-dose vitamin E supplements [33]. Confidence intervals narrowed over the duration of the trial, which suggests this was not a chance finding. Higher or excessive dosages of some antioxidants could theoretically function as pro-oxidants in some situations. Preventing and minimizing adverse effects of conventional treatment appears to be a more promising area for dietary supplement research and should receive more attention [1].

3.7. Repurposed Heart-Healthy Medications (Aspirin, GLP-1 Agonists, Metformin, Statins, etc.)

Standard-of-care preventive cardiovascular medications were of primary interest to this committee [6], especially if they have the potential to prevent lethal prostate cancer or other common carcinomas. It is for this reason 5-alpha-reductase inhibitors are not included in this manuscript.

3.8. Aspirin, Cancer, Lethal Prostate Cancer, and the ADD-ASPIRIN Phase 3 Trial

Aspirin has an accepted role in the prevention of adenoma and colon cancer risk [34,35]. High-dose aspirin has demonstrated the potential to reduce the risk of colorectal and other cancers in Lynch syndrome patients [36]. Thus, the potential for aspirin to prevent aggressive prostate cancer should be pursued and harbors preliminarily encouraging data [37,38,39,40], but increased ancillary adverse events also appear with age [41]. There is an ongoing phase 3 trial known as “ADD-ASPIRIN”, which includes men previously treated for localized prostate cancer with a higher risk of recurrence [42]. Two different aspirin dosages (100 mg and 300 mg based on age of entry) are being tested versus placebo for 5 years, and over 1900 men were randomized. This trial has already demonstrated the ability of aspirin in some patients to inhibit platelet aggregation or thromboxane synthesis (potent pro-inflammatory signals), which could reduce the recurrence risk or progression of some common cancers [43]. This trial will arguably be the most impactful in determining whether aspirin has a role in prostate cancer prevention post-treatment.

3.9. Metformin and GLP-1 Agonists

Metformin did not display an ability to prevent progression in a recent randomized trial (Metformin Active Surveillance Trial [MAST]) of AS patients [44]. However, two other recent notable randomized clinical trials (MANSMED and Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE)) have found the potential to discourage progression in select sub-groups of metastatic hormone-naïve (mHSPC) non-diabetic androgen deprivation therapy (ADT) patients [45,46], and regardless of the outcome, the most methodologically robust trial conducted thus far (STAMPEDE) has documented endpoint evidence of the prevention of several notable metabolic adverse effects of ADT, which could impact cardiovascular events [46]. This is of enormous interest since this low-cost generic heart-healthy medication can also treat and prevent type 2 diabetes in select patients [47]. Still, it is of interest that lifestyle changes have resulted in larger impacts on diabetes prevention versus metformin. However, the potency of metformin for weight loss does not currently compare to the GLP-1 agonist medications (semaglutide, tirzepatide) [48,49]. These novel profound glycemic or weight-loss agents have demonstrated the potential to prevent cardiovascular events in high-risk patients [49]. Average body-weight reductions of 15–20% within 1–2 years profoundly reduces multiple cardiovascular parameters known to increase cardiovascular events. If these medications continue to demonstrate acute and long-term safety, and cost can be profoundly reduced to widen accessibility, it would be one of the more interesting or relevant to test against prostate cancer or to reduce the adverse effects of conventional systemic treatment [48,50].

3.10. Statins (PCSK9 Inhibitors, Other Novel Cholesterol Reducing Compounds, etc.)

The impact of statins on the primary or secondary prevention of cardiovascular events is well known, but the impact on prostate cancer continues to be debated. Still, most of the preliminary evidence suggests an ability to lower the risk of advanced and fatal prostate cancer in men utilizing statins, and an ability to potentially enhance some systemic treatment outcomes, including synergistically delaying recurrence, progression, or the time to treatment resistance, and reducing prostate cancer and overall mortality [4,51,52]. Other novel cholesterol-lowering compounds, such as PCSK9 inhibitors, will hopefully receive some clinical research in the future since they are becoming a standard preventive treatment in cardiovascular medicine.

3.11. Miscellaneous (Environmental, Sleep, etc.)

Multiple diverse interventions were considered by this committee, but most of this research is still embryonic. For example, environmental and occupational conditions exist and should continue to garner interest [53]. Sleep quantity (duration) and quality metrics are gaining momentum in terms of their associations and causation with a variety of cancers, including prostate carcinoma [54,55]. Sleep is associated with numerous conditions, and it was recently added as a behavioral factor to some cardiovascular guidelines that is garnering more research in terms of its relation to heart and overall health [6]. Regardless, in prostate cancer there is insufficient information at this time to suggest not causation, but rather association, but patients should be aware of the preliminary novel evidence to improve cardiovascular health with adequate sleep duration (7–9 h) and improved quality when other lifestyle changes are followed (diet, exercise, etc.) [6].

4. Discussion

Clinicians require more pithy and tangible recommendations that have the highest probability of benefiting their patients not only against prostate cancer but also simultaneously for CVD and all-cause mortality. It is noteworthy that the lifestyle changes and repurposed medications of most promise arguably are identical options to reduce cardiovascular disease events and increase longevity. They are also the same recommendations that can improve mental health and overall quality of life. A summary of these heart-healthy behaviors and medications are found in Table 1.
Still, the primary limitation of the present and past data on lethal prostate cancer should also be highlighted, which is the lack of randomized long-term trials with morbidity and mortality endpoints. This should be expected since ethical issues abound in assigning some individuals to a non-intervention or placebo group since heart healthy and unhealthy behaviors are already well recognized throughout medicine. Asking some participants to engage in non-healthy behaviors is not acceptable. Additionally, utilizing a preventive clinical trial program requires a multitude of participants to achieve appropriate statistical power with an associated intimidating cost difficult to procure in this specific field of medicine. Still, more clinical studies are needed for those at a higher risk of lethal prostate cancer, as are adequately sized long-term prospective studies with numerous evaluation intervals and the pursuit of improved statistical clarity via extensive multivariate analysis.

5. Conclusions of the Committee

Lethal prostate cancer prevention via salubrious cardiovascular-centric lifestyle changes, metrics, and repurposed medications could also favorably impact all-cause morbidity and mortality. Clinicians have a unique and extraordinary opportunity to improve the quality and quantity of patients’ lives via this synergistic approach regardless of the stage of prostate cancer being addressed.

Author Contributions

Conceptualization: M.A.M., R.V.T., D.A.G., D.R.T. and R.U.N.; methodology: M.A.M., R.V.T., D.A.G., D.R.T. and R.U.N.; validation: M.A.M., R.V.T., D.A.G., D.R.T. and R.U.N.; formal analysis: M.A.M., R.V.T., D.A.G., D.R.T. and R.U.N.; resources: M.A.M., R.V.T., D.A.G., D.R.T. and R.U.N.; data curation: M.A.M., R.V.T., D.A.G., D.R.T. and R.U.N.; writing—original draft preparation; M.A.M., R.V.T., D.A.G., D.R.T. and R.U.N.; writing—review and editing: M.A.M. and R.U.N.; supervision: M.A.M. and R.U.N. All authors have read and agreed to the published version of the manuscript.

Funding

This research has no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Acknowledgments

Special thanks to all the members of this unique committee from around the world.

Conflicts of Interest

The authors declare no conflicts of interest.

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Table 1. Potential heart-healthy risk-reducing lifestyle changes, metrics, and medications to reduce the risk of lethal prostate cancer, cardiovascular disease, and all-cause mortality (premature death).
Table 1. Potential heart-healthy risk-reducing lifestyle changes, metrics, and medications to reduce the risk of lethal prostate cancer, cardiovascular disease, and all-cause mortality (premature death).
Greater exercise volume and intensity (aerobic and resistance activities should receive equal awareness to improve mental and physical health). Exercise also discourages muscle (sarcopenia) and bone mineral-density (BMD) loss associated with some forms of prostate cancer treatment (androgen deprivation therapy (ADT)), aging, caloric reduction dietary patterns, and/or weight-loss medications [12,18,19,20,48].
Primarily plant-based dietary patterns, including generally whole, unprocessed, healthier foods and beverages, which supports the consumption of vegetables, fruits, legumes/beans/lentils, whole grains, nuts, seeds, healthy fish, water, tea, coffee, etc., and minimizing processed foods, including red and processed meats, higher-fat dairy, dietary cholesterol, refined grains, sodium-replete products/snacks, sugar-sweetened beverages, etc. [1,21,22]. Also, other dietary patterns associated with an improvement in a patient’s cardiovascular healthy metabolic metrics should be supported based on individual preferences, beliefs, compliance, and mental health/quality-of-life considerations [48].
Alcohol reduction and tobacco elimination [23,24,25,26,27].
Cardiovascular healthy metabolic metrics (weight/waist circumference, blood sugar/insulin sensitivity, cholesterol, blood pressure, inflammatory markers, etc.) [1,2,3,6,28,29,30].
Repurposed medications (aspirin, GLP-1 agonists, metformin, statins, etc.) for those who would qualify based primarily on cardiovascular disease (CVD) risk assessment [1,4,46,47,48,49,51,52]. Prostate cancer research data available recently should soon help further guide this category and discussion (results of ADD-ASPIRIN trial, Metformin Active Surveillance Trial (MAST), Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE), etc.).
Other modifiable changes, such as sleep quality and quantity, may have a future role in prostate cancer risk prevention akin to what has been observed recently in cardiovascular medicine [2,3,6,54,55]. Regardless, healthy sleep is currently associated with the other healthy lifestyle recommendations in this table.
Note: An increased risk of lethal prostate cancer from genetic testing and/or family history continues to support the heart-healthy behaviors and metabolic metrics listed in this table as a potential pathway to reducing this increased risk of lethality and cardiovascular disease events, and improve quality and quantity of life (all-cause mortality) [2,3,6,7,8,9,10,31].
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Moyad, M.A.; Tiwari, R.V.; Galvão, D.A.; Taaffe, D.R.; Newton, R.U. SIU-ICUD: Prevention of Lethal Prostate Cancer via Modifiable Heart-Healthy Lifestyle Changes, Metrics, and Repurposed Medications. Soc. Int. Urol. J. 2025, 6, 40. https://doi.org/10.3390/siuj6030040

AMA Style

Moyad MA, Tiwari RV, Galvão DA, Taaffe DR, Newton RU. SIU-ICUD: Prevention of Lethal Prostate Cancer via Modifiable Heart-Healthy Lifestyle Changes, Metrics, and Repurposed Medications. Société Internationale d’Urologie Journal. 2025; 6(3):40. https://doi.org/10.3390/siuj6030040

Chicago/Turabian Style

Moyad, Mark A., Raj V. Tiwari, Daniel A. Galvão, Dennis R. Taaffe, and Robert U. Newton. 2025. "SIU-ICUD: Prevention of Lethal Prostate Cancer via Modifiable Heart-Healthy Lifestyle Changes, Metrics, and Repurposed Medications" Société Internationale d’Urologie Journal 6, no. 3: 40. https://doi.org/10.3390/siuj6030040

APA Style

Moyad, M. A., Tiwari, R. V., Galvão, D. A., Taaffe, D. R., & Newton, R. U. (2025). SIU-ICUD: Prevention of Lethal Prostate Cancer via Modifiable Heart-Healthy Lifestyle Changes, Metrics, and Repurposed Medications. Société Internationale d’Urologie Journal, 6(3), 40. https://doi.org/10.3390/siuj6030040

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