Several primary prevention strategies, including chemoprevention, prophylactic surgery and lifestyle modifications, have been shown to reduce the risk of breast cancer (BC) and prostate cancer (Pca). However, the uptake of these preventive measures is considered suboptimal, limiting their impact on cancer prevention. A personalised primary prevention strategy has yet to be tested for cancer prevention. Therefore, we aim to determine the feasibility, acceptability and potential benefits and harms of this strategy in women and men at high risk of BC and Pca.

This is a two-arm, parallel-group mixed-methods pilot randomised controlled trial with a 1:1 allocation. The study aims to recruit 60 women and 60 men at high risk of BC and PCa in two specialised sites: the Breast Diseases Center and the Department of Urologic Oncology of the CHU de Québec-Université Laval, Canada. Assessments include intentions to uptake, actual uptake rates of primary preventive measures and decision regret. Feasibility and acceptability of the intervention and the study will be measured by quantifying the recruitment rate, appropriateness of randomisation process and satisfaction metrics. Data will be collected using mixed methods. Quantitative measures will be assessed at baseline and 6 months post randomisation. Quantitative analysis will include descriptive statistics for all variables of interest. Generalised linear mixed models with random intercepts will be used to assess the overall intervention effect. Semistructured interviews will be conducted at the end of follow-up, and a thematic analysis will be performed using NVivo to understand participants' perspectives.

The protocol was approved by the Institutional Review Board of CHU de Québec-Université Laval (4 October 2022; 2023-6315). The findings of the study will be published in a peer-reviewed journal and disseminated at national and international conferences and through social media.

The protocol for this study was registered with the International Clinical Trials Registry (ISRCTN15749766) https://doi.org/10.1186/ISRCTN15749766).

To discuss the overall and latest observations of the effect of diet, lifestyle, supplements, and some prescription heart healthy medications for prostate cancer prevention.

The concept of maximizing heart health to prevent aggressive prostate cancer continues to be solidified with the addition of more prospective observational and randomized controlled trial data. Heart healthy is prostate healthy, but heart unhealthy is prostate unhealthy. The primary goal of reducing the risk of all-cause and cardiovascular disease (CVD) morbidity and mortality also allows for maximizing prostate cancer prevention. The obesity epidemic in children and adults along with recent diverse research has only strengthened the nexus between heart and prostate health. Greater dietary adherence toward a variety of healthy foods is associated with a graded improved probability of CVD and potentially aggressive cancer risk reduction. Preventing prostate cancer via dietary supplements should encourage a "first do no harm", or less is more approach until future evidence can reverse the concerning trend that more supplementation has resulted in either no impact or an increased risk of prostate cancer. Supplements to reduce side effects of some cancer treatments appear to have more encouraging data. Medications that improve heart health including statins, aspirin, and metformin (S.A.M.), and specific beta-blocker medications are primarily generic or low-cost and should continue to garner research interest. A watershed moment in medical education has arrived where the past perception of a diverse number of trees seemingly separated by vast distances, in reality, now appear to exist within the same forest.

Green tea consumption has been shown to possess cancer chemopreventive activity. Polyphenol E (PE) is a widely used standardized green tea extract formulation. This study was designed to investigate the impact of PE on prostate cancer cells (PC3), analyze the potential signals involved and elucidate whether anti- or pro-oxidant effects may be implicated. Treatment of PC3 cells with 30 and 100μg/ml PE significantly decreased cell viability and proliferation. At the tested concentrations, PE did not exert any antioxidant activity, eliciting instead a pro-oxidant effect at concentrations 30 and 100μg/ml, which was consistent with the observed PE cytotoxicity. PE-induced cell death was associated with mitochondrial dysfunction and downregulation of Akt activation, thus suggesting their implication in the PE-elicited cell dysfunction. Cell exposure to the ROS scavenger N-Acetyl Cysteine prevented PE-induced ROS increase, pAkt impairment, and cell death, clearly indicating the causative role of ROS in the observed phenomena. Failure of PE to induce PC3 damage in cells overexpressing Akt further confirms its implication in the PE-elicited cell death. Our findings showed an association between the antiproliferative and the pro-oxidant effect elicited by PE on PC3 cells and delineates a molecular signaling pattern potentially implicated in the toxicity of PE towards prostate cancer cells.

Dietary compounds and epigenetic influences are well recognized factors in cancer progression. Resveratrol (Res), a dietary compound from grapes, has anticancer properties; however, its epigenetic effects are understudied. Metastasis-associated protein 1 (MTA1) is a part of the nucleosome remodeling deacetylation (NuRD) corepressor complex that mediates posttranslational modifications of histones and nonhistone proteins resulting in transcriptional repression. MTA1 overexpression in prostate cancer (PCa) correlates with tumor aggressiveness and metastasis. In this study, we have identified a novel MTA1-mediated mechanism, by which Res restores p53-signaling pathways in PCa cells. We show, for the first time, that Res causes down-regulation of MTA1 protein, leading to destabilization of MTA1/NuRD thus allowing acetylation/activation of p53. We demonstrated that MTA1 decrease by Res was concomitant with accumulation of Ac-p53. MTA1 knockdown further sensitized PCa cells to Res-dependent p53 acetylation and recruitment to the p21 and Bax promoters. Furthermore, MTA1 silencing maximized the levels of Res-induced apoptosis and pro-apoptotic Bax accumulation. HDAC inhibitor SAHA, like MTA1 silencing, increased Res-dependent p53 acetylation and showed cooperative effect on apoptosis. Our results indicate a novel epigenetic mechanism that contributes to Res anticancer activities: the inhibition of MTA1/NuRD complexes due to MTA1 decrease, which suppresses its deacetylation function and allows p53 acetylation and subsequent activation of pro-apoptotic genes. Our study identifies MTA1 as a new molecular target of Res that may have important clinical applications for PCa chemoprevention and therapy, and points to the combination of Res with HDAC inhibitors as an innovative therapeutic strategy for the treatment of PCa.

Prostate-specific health products (dietary supplements) are taken by cancer patients to alleviate the symptoms linked with poor prostate health. However, the effect of these agents on evidence-based radiotherapy practice is poorly understood. The present study aimed to determine whether dietary supplements radiosensitized normal prostate or prostate cancer cell lines.

Three well-known prostate-specific dietary supplements were purchased from commercial sources available to patients (Trinovin, Provelex, and Prostate Rx). The cells used in the study included normal prostate lines (RWPE-1 and PWR-1E), prostate tumor lines (PC3, DU145, and LNCaP), and a normal nonprostate line (HaCaT). Supplement toxicity was assessed using cell proliferation assays [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and cellular radiosensitivity using conventional clonogenic assays (0.5-4Gy). Cell cycle kinetics were assessed using the bromodeoxyuridine/propidium iodide pulse-labeling technique, apoptosis by scoring caspase-3 activation, and DNA repair by assessing gammaH2AX.

The cell growth and radiosensitivity of the malignant PC3, DU145, and LNcaP cells were not affected by any of the dietary prostate supplements (Provelex [2 microg/mL], Trinovin [10 microg/mL], and Prostate Rx [50 microg/mL]). However, both Trinovin (10 microg/mL) and Prostate Rx (6 microg/mL) inhibited the growth rate of the normal prostate cell lines. Prostate Rx increased cellular radiosensitivity of RWPE-1 cells through the inhibition of DNA repair.

The use of prostate-specific dietary supplements should be discouraged during radiotherapy owing to the preferential radiosensitization of normal prostate cells.

It has been long appreciated that a healthy lifestyle plays a critical role in cardiovascular health. It is now apparent that the same is true in the development of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Since 1995, 14 studies have been identified that investigate the clinical relationship between exercise and BPH/LUTS. No randomized controlled trials have been performed, but useful prospective cohort data originating from recent publications on the medical treatment of BPH and prevention of prostate cancer are available. Most of the literature supports a clinically significant, independent, and strong inverse relationship between exercise and the development of BPH/LUTS. Several mechanisms for this relationship have been proposed, including decreased sympathetic tone, avoidance of metabolic syndrome, and reduced oxidative damage to the prostate.

With emerging trends in the incidence of cancer of various organ sites, additional approaches are needed to control human malignancies. Intervention or prevention of cancer by dietary constituents, a strategy defined as chemoprevention, holds great promise in our conquest to control cancer, because it can be implemented on a broader population base with less economic burden. Consistent with this, several epidemiological studies have shown that populations that consume diets rich in fruits and vegetables have an overall lower cancer incidence. Based on these encouraging observations, research efforts from across the globe have focused on identifying, characterizing, and providing scientific basis to the efficacy of various phytonutrients in an effort to develop effective strategy to control various human malignancies. Cancer induction, growth, and progression are multi-step events and numerous studies have demonstrated that various dietary agents interfere with these stages of cancer, thus blocking malignancy. Fruits and vegetables represent untapped reservoir of various nutritive and nonnutritive phytochemicals with potential cancer chemopreventive activity. Grapes and grape-based products are one such class of dietary products that have shown cancer chemopreventive potential and are also known to improve overall human health. This review focuses on recent advancements in cancer chemopreventive and anticancer efficacy of grape seed extract and other grape-based products. Overall, completed studies from various scientific groups conclude that both grapes and grape-based products are excellent sources of various anticancer agents and their regular consumption should thus be beneficial to the general population.

Patients facing medical decisions that will impact quality of life make assumptions about how they will adjust emotionally to living with health declines and disability. Despite abundant research on decision-making, we have no direct research on how accurately patients envision their future well-being and how this influences their decisions. Outside medicine, psychological research on "affective forecasting" consistently shows that people poorly predict their future ability to adapt to adversity. This finding is important for medicine, since many serious health decisions hinge on quality-of-life judgments. We describe three specific mechanisms for affective forecasting errors that may influence health decisions: focalism, in which people focus more on what will change than on what will stay the same; immune neglect, in which they fail to envision how their own coping skills will lessen their unhappiness; and failure to predict adaptation, in which people fail to envision shifts in what they value. We discuss emotional and social factors that interact with these cognitive biases. We describe how caregivers can recognize these biases in the clinical setting and suggest interventions to help patients recognize and address affective forecasting errors.

Genetic testing for hereditary cancer facilitates medical management and improves health outcomes. Genetic testing is not currently available for prostate cancer, but trials are underway to investigate if antiandrogens and selenium have a preventive role for at-risk individuals. To inform future genetic counseling, we sought to understand the pre-existing beliefs and behaviors of men with a family history of prostate cancer and explore their intention to adopt possible preventive behaviors in response to test results.

A survey was completed by 280 men (response: 59%).

The belief that diet influenced prostate cancer risk was held by 73% of participants, whereas 37% believed in medication/natural therapies. Thirty-nine percent reported at least one change to their diet, alcohol consumption, smoking, exercise patterns, vitamin/mineral/supplement intake and/or medication/natural therapy in response to their family history. The men expressed interest in genetic testing with 92% "definitely" or "probably" interested. Definite interest was associated with number of affected relatives and prostate cancer-related anxiety. A positive genetic test would motivate 93% of men to make at least one behavioral change.

Participants commonly believed behavioral factors influenced prostate cancer risk and reported that they would alter their behavior to reduce risk after (hypothetical) genetic testing.

Deregulation of the estrogen axis in humans prompts a series of tissue-specific events. In the breast and prostate, alterations in estrogen signalling lead to genotypic and phenotypic molecular alterations that result in dysplastic cellular appearance, deregulated cell growth and carcinoma. In bone, decreased estrogen leads to increased osteoclastogenesis and bone resorption, decreased bone mineral density and a significant fracture risk. Toremifene is a selective estrogen receptor modulator that exerts pharmacological activity in the breast, bone and prostate. An intense interest in developing this agent for prostate cancer chemoprevention is based on the reduction of premalignant and malignant prostate lesions in a transgenic model of prostate cancer. Biological and clinical activity was demonstrated in Phase II trials by the prevention of progression to prostate cancer in men with high-grade prostate intraepithelial neoplasia and through suppression of bone turnover biomarkers and increased bone mineral density in men on androgen deprivation therapy for prostate cancer.

Previous research on cancer information focused on active seeking, neglecting information gathered through routine media use or conversation ("scanning"). It is hypothesized that both scanning and active seeking influence knowledge, prevention, and screening decisions. This study uses Health Information National Trends Survey (HINTS, 2003) data to describe cancer-related scanning and seeking behavior (SSB) and assess its relationship with knowledge, lifestyle behavior, and screening. Scanning was operationalized as the amount of attention paid to health topics, and seeking was defined as looking for cancer information in the past year. The resulting typology included 41% low-scan/no-seekers; 30% high-scan/no-seekers; 10% low-scan/seekers, and 19% high-scan/seekers. Both scanning and seeking were significantly associated with knowledge about cancer (B=.36; B=.34) and lifestyle choices that may prevent cancer (B=.15; B=.16) in multivariate analyses. Both scanning and seeking were associated with colonoscopy (OR = 1.38, for scanning and OR=1.44, for seeking) and with prostate cancer screening (OR=4.53, scanning; OR=10.01, seeking). Scanning was significantly associated with recent mammography (OR=1.46), but seeking was not. Individuals who scan or seek cancer information are those who acquire knowledge, adopt healthy lifestyle behaviors, and get screened for cancer. Causal claims about these associations await further research.

Complementary and alternative medicine (CAM) includes various practices, measures and products which are not presently considered to be a part of conventional (mainstream) medicine. Herbal products, vitamins, minerals and amino acids are increasingly popular as dietary supplements for the treatment, improvement and prophylaxis of urological diseases, and to improve general health and well-being. As these products are freely available without prescription, conventional healthcare providers are often unaware that their patients are using CAM. It is essential to know that some herbal supplements may act in the same way as chemical drugs, and that they originate 'from nature' does not mean that they are safe and/or with no potential harmful effects and/or toxicity. Eventual interactions with conventional medications and contamination with prescription drugs and metals have been reported. The active components of many phytotherapeutic preparations and their mechanism(s) of action are still being determined and evaluated. There is scientific evidence for the effectiveness of some CAM treatments, but for most there are important key questions yet to be answered through basic research and well-designed studies according to established guidelines. Because of the increasing popularity and use of CAM, conventional healthcare providers, including urologists, should not ignore it, and be well informed about the benefits and potential risks of dietary supplements, so that they can advise their patients about this developing field. Whenever necessary and possible, lifestyle and behavioural changes should be recommended before using CAM, and eventually be supplemented by CAM as a second step.

Several important observations should be kept in mind by cancer researchers: cardiovascular disease (CVD) is the number one cause of death; CVD is the number one cause of death in the largest cancer chemoprevention trials; CVD is the number one or two cause of death in prostate cancer patients; and some of the mechanisms that increase the risk of CVD may also increase the risk or progression of prostate cancer.

Screening studies suggest a high prevalence of dyslipidemia in men with and without prostate cancer. Numerous recent lifestyle interventions that reduce cholesterol have also been found to have a potential impact on reducing the risk of prostate cancer. Recent studies of statins and other heart healthy agents have found a secondary potential for exhibiting a reduced risk or progression of prostate cancer.

Laboratory and clinical data over the past several decades continue to support the use of a heart healthy agent in the nest cancer chemoprevention trial. The potential for an agent to simultaneously reduce the risk of the primary and secondary cause of death suggests that statins and other heart healthy agents are the ideal next interventions to be utilized in the next major cancer chemoprevention trial. If successful, this agent would most likely represent a dramatic impact on the history of cancer chemoprevention, and if not successful the potential secondary impact would again be a landmark finding in cancer chemoprevention; so the time is more than ripe for such a unique trial.

Androgen deprivation for prostate cancer use to be applied only in the latter stage of the disease process, thus, the issue of promoting general health during this time was not a concern because the subject of life and death was more paramount. However, thanks to earlier detection of prostate cancer, there has been a general stage migration in this disease. Men are choosing these traditionally late stage therapies earlier and earlier. Therefore, the subject of quality of life on this treatment has now garnered as much attention as the survival issues. Cognitive or mental health concerns, cholesterol changes, hot flashes, osteoporosis, and other side effects are being addressed and treated with a variety of conventional medicines. However, the issue of the role of the patient or what men can do personally to promote better mental and physical health is desperately needed in this area. A variety of beneficial lifestyle changes and over-the-counter agents may have an enormous impact on men's health during androgen deprivation. Calcium and vitamin D supplements, aerobic and resistance exercise, cholesterol awareness and reduction, weight loss, and other individual changes could have an enormous impact on the quality and quantity of a man's life. Some of these so called "bottom line" recommendations are reviewed in this article to empower the patient during this time, and to send clearly the message that he has a role to play apart from just picking up and using a prescription drug for side effects, and his role is just as critical for improving the probability of living longer and better.

Specific ongoing observations from diverse medical studies do not serve to belittle the impact of prostate or other cancers, but the overall impact of cardiovascular disease (CVD) in individuals at high-risk or in individuals that have been diagnosed with common cancers needs to be addressed by future research. CVD has been the number one cause of death in men and women since the year 1990. Serum cholesterol levels are some of the most accurate long-term predictors of all-cause mortality. CVD has been the number one cause of death in the largest dietary supplement cancer chemoprevention trials.

The potential for utilizing a cancer chemoprevention agent that may simultaneously reduce the risk of CVD and cancer is not only attractive, but several agents are available immediately that may demonstrate this unique impact. For example, recently statin drugs, low-dose aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), and even fish oil supplements may be utilized in the next major cancer chemoprevention trial.

Heart healthy agents and interventions seem to also exhibit the ability to be prostate healthy. In addition, their low cost and potential to reduce all-cause mortality may also ensure good compliance. Statins and other heart healthy agents should be considered to be the next most ideal interventions to be utilized in the next major chemoprevention trial, especially now because several popular past dietary supplements and drugs have demonstrated the potential for notable side effects and an inability to impact the risk of CVD.

The recent removal of refecoxib (a cyclo-oxygenase II inhibitor), a drug involved in a large prostate cancer chemoprevention trial, and the completion of recruitment for the SELECT cancer chemoprevention trial utilizing selenium and vitamin E should lead researchers to ponder a similar question in cancer chemoprevention. The question of "What agent should be utilized and what clinical trial should designed and conducted next for cancer chemoprevention?" Part I and II of this manuscript attempts to argue that statins or cholesterol-lowering drugs or heart healthy agents are the ideal next choice for a large chemoprevention trial for numerous reasons including: (1) Cardiovascular disease (CVD) has been the number one cause of death in men and women every year in the US since 1900; (2) CVD has been the number one cause of death in the major cancer chemoprevention trials; (3) CVD has been the number one or two cause of death of men and women postdiagnosis of breast, colorectal, and prostate cancer; and (4) the recent potential relationship between certain cancers and dyslipidemia needs to be investigated. What other chemoprevention agent can also boast that in the worst case scenario the number one cause of death in men and women would probably be reduced in this future cancer chemoprevention trial of statins?! The list continues to grow of cancer chemoprevention trials that will probably be either a complete hit or miss. In other words, they will or have reduced the disease of interest with virtually no potential role for reducing the number one cause of death in men and women. The time seems more than overdue for a statin and/or another cholesterol lowering or heart healthy cancer chemoprevention trial.

The optimal treatment strategy for patients with high-risk localized prostate cancer remains unknown. Definitive local treatments such as radical prostatectomy and external beam radiotherapy cure only a minority of these patients. Recent efforts have been made to reduce the risk of recurrence and delay progression to symptomatic hormone-refractory disease by using chemotherapy before, during, or after definitive local therapy. Chemotherapy is an effective modality in the treatment of hormone- refractory prostate cancer. Studies have established its role in the palliation of symptoms in patients with hormone-refractory disease, though a survival benefit remains to be demonstrated. Prospective randomized trials are underway to test the hypothesis that neoadjuvant and adjuvant chemotherapy may improve survival rate in patients with high-risk localized prostate cancer. The data currently available from nonrandomized trials have not yet established the exact role of neoadjuvant and adjuvant chemotherapy and its potential impact on survival. However, preliminary data suggest that chemotherapy, when administered in concert with definitive local therapy, may be promising in patients with locally advanced prostate cancer. Randomized clinical trials are ongoing to see if neoadjuvant and adjuvant chemotherapy will translate into an improved clinical benefit for the patient, and participation by patients is paramount. We review the recent literature regarding the use of neoadjuvant and adjuvant chemotherapy in patients with locally advanced prostate cancer.