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Impact of lifestyle in prostate cancer patients. What should we do?

ABSTRACT

Objective:

This review aimed to analyze interventions raised within primary and tertiary prevention concerning the disease's incidence, progression, and recurrence of Prostate Cancer (PCa). Priority was given to the multidisciplinary approach of PCa patients with an emphasis on modifiable risk factors.

Materials and Methods:

We conducted a comprehensive literature review in the following databases: Embase, Central, and Medline. We included the most recent evidence assessing cohort studies, case-control studies, clinical trials, and systematic reviews published in the last five years. We only included studies in adults and in vitro or cell culture studies. The review was limited to English and Spanish articles.

Results:

Preventive interventions at all levels are the cornerstone of adherence to disease treatment and progression avoidance. The relationship in terms of healthy lifestyles is related to greater survival. The risk of developing cancer is associated to different eating habits, determined by geographic variations, possibly related to different genetic susceptibilities.

Discussion:

PCa is the second most common cancer in men, representing a leading cause of death among men in Latin America. Prevention strategies and healthy lifestyles are associated with higher survival rates in PCa patients. Also, screening for anxiety and the presence of symptoms related to mood disorders is essential in the patient's follow-up concerning their perception of the condition.

Keywords:
Prostatic Neoplasms; Healthy Lifestyle; Diet

INTRODUCTION

Cancer causes significant social and economic impacts, leading to 672.758 deaths per year worldwide. The increase in morbidity and mortality is directly related to the change in population distribution (11 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69:7-34.). Among the strongly linked factors, aging, increase in population life expectancy, better socioeconomic development worldwide, and the variable profile of pathologies stand out, placing cancer among the leading causes of death in the population (11 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69:7-34.).

Prostate cancer (PCa) is the second most common cancer in men, with a peak presentation between 65 and 70 years of age. It represents the leading cause of death among Latin American and Caribbean men (5656 Benke IN, Leitzmann MF, Behrens G, Schmid D. Physical activity in relation to risk of prostate cancer: a systematic review and meta-analysis. Ann Oncol. 2018; 29:1154-79..44 Bell KJ, Del Mar C, Wright G, Dickinson J, Glasziou P. Prevalence of incidental prostate cancer: A systematic review of autopsy studies. Int J Cancer. 2015; 137:1749-57. Age-Standardized Rate (ASR) per 100000) (22 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68:394-424. Erratum in: CA Cancer J Clin. 2020; 70:313.). It has a multifactorial and polygenetic etiology. Its incidence and prevalence are linked to modifiable and non-modifiable risk factors, which have been studied in different population groups. Non-modifiable factors include African descent and a family history of PCa; susceptibility is also described in individuals expressing certain genetic profiles. Among the modifiable factors, diet, exercise, toxic exposures, and behavioral measures have been linked to differences in PCa prognosis (33 Finlay A, Wittert G, Short CE. A systematic review of physical activity-based behaviour change interventions reaching men with prostate cancer. J Cancer Surviv. 2018; 12:571-91.). In 2019, an estimate of 174.650 new PCa cases were diagnosed in the United States, representing one case for every five new cancer diagnoses, constituting a public health problem in the male population (11 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69:7-34., 44 Bell KJ, Del Mar C, Wright G, Dickinson J, Glasziou P. Prevalence of incidental prostate cancer: A systematic review of autopsy studies. Int J Cancer. 2015; 137:1749-57.). In Latin America, 190.385 new cases (27.9%) were reported (22 Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68:394-424. Erratum in: CA Cancer J Clin. 2020; 70:313.). To reduce the social and economic impact on the population, guidelines have established primary, secondary, and tertiary prevention strategies (33 Finlay A, Wittert G, Short CE. A systematic review of physical activity-based behaviour change interventions reaching men with prostate cancer. J Cancer Surviv. 2018; 12:571-91., 55 Ballon-Landa E, Parsons JK. Nutrition, physical activity, and lifestyle factors in prostate cancer prevention. Curr Opin Urol. 2018; 28:55-61.). In Latin America, prevention programs are heterogeneous due to the structure and accessibility of the different health systems.

This review focused on analyzing interventions raised within primary and tertiary prevention concerning the disease's incidence, progression, and recurrence of PCa. Priority was given to the multidisciplinary approach of PCa patients with an emphasis on modifiable risk factors.

Acquisition of evidence

A comprehensive literature search was carried out in the following databases: Embase, Central, and Medline. We included studies that established the relationship between PCa and molecular factors, changes in diet (including dietary patterns, group relationship of macromolecules, vitamins, and micronutrients), exercise, mental health and work, and multimodal therapy; in terms of prevention, impact on morbidity-mortality and as part of treatment. We used MeSH terms related to PCa: “prostate cancer”, “prostate neoplasm” and for lifestyle both MeSH and free language terms were used for: exercise (“physical activity”, “aerobic exercise”, “exercise”, “training”); diet (“diet habit”, “diet modification”); mental health and work (“anxiety”, “mental health”, “depression”, “work”, “professional burnout”, “acute stress disorder”; and multimodal treatment (Supplementary material 1). We included the most recent evidence assessing cohort studies, case-control studies, clinical trials, and systematic reviews published in the last five years until September 2020. We only included studies in adults and in vitro or cell culture studies. The review was limited to English and Spanish articles. We included a few studies before five years, according to their relevance.

Evidence synthesis

Molecular basis for the impact of lifestyle on PCa

We reviewed the molecular impact of lifestyle variation in subjects diagnosed with PCa. Those studies indicate that certain oncogenic factors are related to pro-inflammatory mechanisms, generating variations in the cellular cycle (Table-1). Among these factors are continuous exposure to androgens, insulin-like growth factor (IGF-1), vasoactive peptides, and reactive oxygen species (ROS) related to apoptosis inhibition. These enhanced abnormal cell signaling pathways overexpress angiogenesis mechanisms and cause disease progression (66 Pernar CH, Ebot EM, Pettersson A, Graff RE, Giunchi F, Ahearn TU, et al. A Prospective Study of the Association between Physical Activity and Risk of Prostate Cancer Defined by Clinical Features and TMPRSS2:ERG. Eur Urol. 2019; 76:33-40., 77 Thomas RJ, Kenfield SA, Jimenez A. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review. Br J Sports Med. 2017; 51:640-4.).

Table 1
Summary of the pathogenesis of molecular factors that are related to environmental factors such as diet and physical activity.

DNA methylation, non-histone protein expression, and telomerase activity are modified under continuous exposure to ROS. Regular physical activity, and a diet low in carbohydrates and saturated fats are linked to suitable DNA structural repair. A prospective study has shown the relationship between vigorous physical activity and progression to metastatic PCa. Patients with regular physical activity one year before diagnosis showed decreased methylation of the promoter regions related to the CRACR2A gene. This gene encodes a calcium-binding protein, involved in the innate immune response, related with carcinogenesis mechanisms (88 Dai JY, Wang B, Wang X, Cheng A, Kolb S, Stanford JL, et al. Vigorous Physical Activity Is Associated with Lower Risk of Metastatic-Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene. Cancer Epidemiol Biomarkers Prev. 2019; 28:258-64.). Nevertheless, DNA structure hypomethylation is associated with a lower risk of progression. Thomas et al. found that sedentary patients, with high stress levels, overexpressed histone acetylation with excessive RAS oncogene family levels, which resulted in an increased cell proliferation. Also, microRNA (miRNA) generated cell signaling changes concerning the expression and coordination of p53 gene activity, concluding that physical activity is significantly related to epigenetic factors (77 Thomas RJ, Kenfield SA, Jimenez A. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review. Br J Sports Med. 2017; 51:640-4.).

Qin et al. found that prostate cancer antigen 3 (PCA3) distinguishes healthy patients from patients with PCa; this biomarker is over-expressed in more than 95% of PCa cells. The influence of ethnicity on PCA3 is not clear; we need more studies to conclude differential diagnosis of PCa (99 Qin Z, Yao J, Xu L, Xu Z, Ge Y, Zhou L, et al. Diagnosis accuracy of PCA3 level in patients with prostate cancer: a systematic review with meta-analysis. Int Braz J Urol. 2020; 46:691-704.1111 Favorito LA. Increase in submissions to International Brazilian Journal of Urology during Covid-19 quarentine. Int Braz J Urol. 2020; 46:689-90.).

Patients with locally advanced PCa, in whom vigorous physical activity and absence of tobacco use was documented, had longer and more stable telomeres. Besides, they had a reduction in prostate-specific antigen (PSA) levels compared to sedentary patients. Increased expression of vasoactive intestinal peptide (VIP), which promotes angiogenesis, is related to rapid disease progression in patients with resistance to hormone therapy (88 Dai JY, Wang B, Wang X, Cheng A, Kolb S, Stanford JL, et al. Vigorous Physical Activity Is Associated with Lower Risk of Metastatic-Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene. Cancer Epidemiol Biomarkers Prev. 2019; 28:258-64.).

On the other hand, elevated testosterone levels are linked to an increase in PCa incidence. Physical activity, approximately 15 minutes to an hour, is known to increase testosterone levels quickly; however, increased levels are not related to free testosterone. They are directly related to higher protein-bound levels, which are biologically inactive. Over time, moderate to intense regular exercise reduces testosterone, generating negative feedback by blocking luteinizing and follicle stimulating hormones (77 Thomas RJ, Kenfield SA, Jimenez A. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review. Br J Sports Med. 2017; 51:640-4., 88 Dai JY, Wang B, Wang X, Cheng A, Kolb S, Stanford JL, et al. Vigorous Physical Activity Is Associated with Lower Risk of Metastatic-Lethal Progression in Prostate Cancer and Hypomethylation in the CRACR2A Gene. Cancer Epidemiol Biomarkers Prev. 2019; 28:258-64.).

Plant consumption was also related to increased expression of Interleukin 2 (IL-2). It promotes the innate immune response, generating adequate activity in natural killer (NK) and T cells. Patients with rich intake of cruciferous vegetables and isothiocyanates have a decreased expression of Interleukin 6 (IL-6) and Tumor Necrosis Factor (TNF), associated with the inhibition of caspase activation (77 Thomas RJ, Kenfield SA, Jimenez A. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review. Br J Sports Med. 2017; 51:640-4., 1212 Vance TM, Azabdaftari G, Pop EA, Lee SG, Su LJ, Fontham ET, et al. Intake of dietary antioxidants is inversely associated with biomarkers of oxidative stress among men with prostate cancer. Br J Nutr. 2016; 115:68-74.).

At the molecular level, changes in diet and physical activity involving aerobic and anaerobic exercise on an ongoing basis (metabolic equivalents [MET] needed to perform the activity ≥6) are related to a modification in the hormonal and anti-inflammatory pathways. Regular physical activity alters endogenous hormone levels, reducing the availability of growth factors such as IGF-1, and decreasing cellular stress. No significant associations were found between total physical activity and PCa risk; however, men with vigorous physical activity continue to have a 30% lower risk of advanced PCa and a 25% lower risk of lethal PCa. The most common molecular subtype of PCa is related to the TMPRSS2:ERG gene fusion. Genetic expression of the TMPRSS2:ERG fusion gene is lower in men who perform vigorous physical activity compared to those who are sedentary (66 Pernar CH, Ebot EM, Pettersson A, Graff RE, Giunchi F, Ahearn TU, et al. A Prospective Study of the Association between Physical Activity and Risk of Prostate Cancer Defined by Clinical Features and TMPRSS2:ERG. Eur Urol. 2019; 76:33-40.).

On the other hand, sleep quality has been shown to have a buffering impact on cortisol levels. In a group of patients diagnosed with localized PCa, low cortisol levels were associated with depressive symptoms (1313 Hoyt MA, Bower JE, Irwin MR, Weierich MR, Stanton AL. Sleep quality and depressive symptoms after prostate cancer: The mechanistic role of cortisol. Behav Neurosci. 2016; 130:351-6.); also, low sleep quality was significantly associated to worse prognosis. These results suggest that the relationship between sleep quality and depressive symptoms may be partially explained by the altered circadian release of cortisol, influencing the inflammatory cascade that enhances disease progression and early mortality (1313 Hoyt MA, Bower JE, Irwin MR, Weierich MR, Stanton AL. Sleep quality and depressive symptoms after prostate cancer: The mechanistic role of cortisol. Behav Neurosci. 2016; 130:351-6.).

Diet and PCa

Multiple studies have struggled to find the relationship between different dietary components and PCa at various disease stages. Also, different authors have searched the association between the impact of prevention strategies on PCa patients (Table-2).

Table 2
Summary with reviews that support intervention by food groups, discriminated by author, type of study, and intervention.

Carbohydrates

The role of simple carbohydrate consumption has been highlighted for its ability to generate hyperinsulinemia and obesity; likewise, insulin has been associated with tumor development. Previous studies related to ketogenic non-carbohydrate diets show decreased tumor growth in mice, similar to what is found in other low-carb diets, such as the Atkins diet (1414 Masko EM, Thomas JA 2nd, Antonelli JA, Lloyd JC, Phillips TE, Poulton SH, et al. Low-carbohydrate diets and prostate cancer: how low is “low enough”? Cancer Prev Res (Phila). 2010; 3:1124-31., 1515 Masko EM, Allott EH, Freedland SJ. The relationship between nutrition and prostate cancer: is more always better? Eur Urol. 2013; 63:810-20.).

Fabiani et al. found that a carbohydrate diet pattern was associated with an increased risk of PCa (OR: 1.64) (1616 Fabiani R, Minelli L, Bertarelli G, Bacci S. A Western Dietary Pattern Increases Prostate Cancer Risk: A Systematic Review and Meta-Analysis. Nutrients. 2016; 8:626.). However, the effects of IGF-1 have been controversial. According to Jayedi et al., increases in fasting blood glucose were not associated with an increased risk of PCa. Nonetheless, other studies show that the effect of blood glucose and diabetes on PCa is time-dependent. Thus, there could be a reduction of up to 12% in patients with type 2 diabetes mellitus (DM2). Consequently, similar survival may be seen in patients with or without DM2 (1717 Jayedi A, Djafarian K, Rezagholizadeh F, Mirzababaei A, Hajimohammadi M, Shab-Bidar S. Fasting blood glucose and risk of prostate cancer: A systematic review and meta-analysis of dose-response. Diabetes Metab. 2018; 44:320-7., 1818 Karlin NJ, Amin SB, Verona PM, Kosiorek HE, Cook CB. Co-existing prostate cancer and diabetes mellitus: implications for patient outcomes and care. Endocr Pract. 2017; 23:816-21.).

Proteins

Proteins may be involved in tumor development or progression. Cooking red meats can lead to the formation of heterocyclic amines, which are mutagenic compounds that are generated when creatine, amino acids, and sugars are subjected to high temperatures. These compounds can trigger genomic instability from direct DNA damage, and a dose-response effect has been identified in PCa (1919 Cross AJ, Peters U, Kirsh VA, Andriole GL, Reding D, Hayes RB, et al. A prospective study of meat and meat mutagens and prostate cancer risk. Cancer Res. 2005; 65:11779-84., 2020 Koutros S, Cross AJ, Sandler DP, Hoppin JA, Ma X, Zheng T, et al. Meat and meat mutagens and risk of prostate cancer in the Agricultural Health Study. Cancer Epidemiol Biomarkers Prev. 2008; 17:80-7.). Other animal proteins, such as fatty fish, have not shown an association with an increased risk of PCa but could reduce the risk of cancer-specific death (2121 Szymanski KM, Wheeler DC, Mucci LA. Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr. 2010; 92:1223-33.). Soy contains high amounts of phytoestrogens, which can block the estrogen receptor, decrease proliferation, and increase cell differentiation, which would contribute to PCa prevention, consistent with findings from a recent meta-analysis showing a significant association between soy consumption and a lower risk of PCa (2222 Hwang YW, Kim SY, Jee SH, Kim YN, Nam CM. Soy food consumption and risk of prostate cancer: a meta-analysis of observational studies. Nutr Cancer. 2009; 61:598-606., 2323 Applegate CC, Rowles JL, Ranard KM, Jeon S, Erdman JW. Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis. Nutrients. 2018; 10:40.).

The evidence is controversial, showing an association with PCa, but not with the aggressiveness or lethality (1515 Masko EM, Allott EH, Freedland SJ. The relationship between nutrition and prostate cancer: is more always better? Eur Urol. 2013; 63:810-20.). The relative risk (RR) of PCa associated with milk and dairy consumption has increased since the first studies, and the most recent meta-analysis reports an RR of 1.50 (IC95% 1.03-2.17) for whole milk. Thus, its use showed a high risk of prostate cancer mortality (RR 1.43 IC95% 1.13-1.81) (2424 Bermejo LM, López-Plaza B, Santurino C, Cavero-Redondo I, Gómez-Candela C. Milk and Dairy Product Consumption and Bladder Cancer Risk: A Systematic Review and Meta-Analysis of Observational Studies. Adv Nutr. 2019; 10(suppl_2):S224-S238., 2525 Lu W, Chen H, Niu Y, Wu H, Xia D, Wu Y. Dairy products intake and cancer mortality risk: a meta-analysis of 11 population-based cohort studies. Nutr J. 2016; 15:91.).

Fats

So far, studies have found no association between overall fat consumption and PCa risk. However, consumption of saturated fats could be associated with an increased risk of biochemical recurrence following prostatectomy, along with an increased risk of advanced PCa (2626 Strom SS, Yamamura Y, Forman MR, Pettaway CA, Barrera SL, DiGiovanni J. Saturated fat intake predicts biochemical failure after prostatectomy. Int J Cancer. 2008; 122:2581-5., 2727 Gathirua-Mwangi WG, Zhang J. Dietary factors and risk for advanced prostate cancer. Eur J Cancer Prev. 2014; 23:96-109.). On the other hand, the increased proportion of unsaturated Omega-6 fats versus Omega-3s has been associated with an increased risk of PCa. This is due to the conversion of arachidonic acid into other compounds that promote inflammation and cell growth (2828 Berquin IM, Edwards IJ, Kridel SJ, Chen YQ. Polyunsaturated fatty acid metabolism in prostate cancer. Cancer Metastasis Rev. 2011; 30:295-309.). Omega-3, on the other hand, has anti-inflammatory, antiproliferative, antiangiogenic, and proapoptotic effects, which place it as an excellent anti-tumor molecule (2929 Williams CD, Whitley BM, Hoyo C, Grant DJ, Iraggi JD, Newman KA, et al. A high ratio of dietary n-6/n-3 polyunsaturated fatty acids is associated with increased risk of prostate cancer. Nutr Res. 2011; 31:1-8.). Cholesterol can be a risk factor for the development of solid tumors due to pro-inflammatory pathway activation and intratumor steroidogenesis. In addition, low-density lipoproteins have been involved in the PCa onset and progression. Hence, some studies indicate that statins could prevent progression but not initiation of PCa (1515 Masko EM, Allott EH, Freedland SJ. The relationship between nutrition and prostate cancer: is more always better? Eur Urol. 2013; 63:810-20., 3030 Li B, Huang D, Zheng H, Cai Q, Guo Z, Wang S. Preoperative serum total cholesterol is a predictor of prognosis in patients with renal cell carcinoma: a meta- analysis of observational studies. Int Braz J Urol. 2020; 46:158-68.). Lippi et al. found a positive correlation between the intake of fried products and the risk of PCa, although the evidence was inconclusive (3131 Lippi G, Mattiuzzi C. Fried food and prostate cancer risk: systematic review and meta-analysis. Int J Food Sci Nutr. 2015; 66:587-9.).

Vegetables

Epidemiological studies have found an inverse relationship between consumption of cruciferous vegetables (such as broccoli or cauliflower) and the risk of PCa. Isothiocyanates in this group of vegetables can suppress cell growth by inhibiting androgen receptor transcription (3232 Wang LG, Liu XM, Chiao JW. Repression of androgen receptor in prostate cancer cells by phenethyl isothiocyanate. Carcinogenesis. 2006; 27:2124-32. Erratum in: Carcinogenesis. 2007; 28:767., 3333 Liu B, Mao Q, Cao M, Xie L. Cruciferous vegetables intake and risk of prostate cancer: a meta-analysis. Int J Urol. 2012; 19:134-41.). Furthermore, vegetables of the genus Allium (e.g., onion, garlic) can stimulate the immune system, inhibit cell growth, modulate the expression of androgen-responding genes and induce apoptosis, playing a protective role against PCa (3434 Chan R, Lok K, Woo J. Prostate cancer and vegetable consumption. Mol Nutr Food Res. 2009; 53:201-16.).

Vitamins and minerals

There is no clarity regarding vitamin B; however, evidence suggests that folate depletion could decrease tumor growth (3535 Tomaszewski JJ, Cummings JL, Parwani AV, Dhir R, Mason JB, Nelson JB, et al. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate. Prostate. 2011; 71:1287-93.).

Similar effects have been attributed to vitamin C due to its antioxidant properties and its ability to reduce oxidative stress, which is an essential factor in cancer initiation and progression. However, randomized clinical trials have shown no effect on PCa (3636 Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, MacFadyen J, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2009; 301:52-62.).

Whereas low vitamin D consumption may be associated with an increased risk of PCa mortality, no significant association with regard to its role in prevention or progression has been demonstrated (3737 Gilbert R, Martin RM, Beynon R, Harris R, Savovic J, Zuccolo L, et al. Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis. Cancer Causes Control. 2011; 22:319-40.). Vitamin E supplementation was associated with an increased risk of cancer, although this was only evidenced in one study (3838 Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011; 306:1549-56.). By decreasing calcium bioavailability, vitamin K would expectedly be a protective factor in PCa, which was found in a cohort study (1515 Masko EM, Allott EH, Freedland SJ. The relationship between nutrition and prostate cancer: is more always better? Eur Urol. 2013; 63:810-20., 3939 Nimptsch K, Rohrmann S, Linseisen J. Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr. 2008; 87:985-92.). Despite these studies, neither the use of multivitamin supplements nor individual vitamin or mineral supplementation affect the incidence of death from PCa (4040 Stratton J, Godwin M. The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis. Fam Pract. 2011; 28:243-52.).

Phytochemicals

Epigallocatechin-gallate is the most abundant phytochemical of green tea, and its role in the reduction of PCa tumor growth has been reported. Other mechanisms, such as proapoptotic pathway induction, decreased inflammation through NF-kB, and antioxidant properties, have also been found. Its consumption could be associated with a lower incidence of PCa and a lower progression of precancerous lesions in a dose-dependent form (1515 Masko EM, Allott EH, Freedland SJ. The relationship between nutrition and prostate cancer: is more always better? Eur Urol. 2013; 63:810-20.).

Similarly, coffee has been inversely associated with PCa risk due to its caffeine content and other antioxidants (4141 Shafique K, McLoone P, Qureshi K, Leung H, Hart C, Morrison DS. Coffee consumption and prostate cancer risk: further evidence for inverse relationship. Nutr J. 2012; 11:42.). In the latest meta-analysis carried out by Xia et al., it was found that coffee consumption could reduce the risk of localized PCa (RR 0.90, IC95% 0.84-0.97) (4242 Xia J, Chen J, Xue JX, Yang J, Wang ZJ. An Up-to-date Meta-analysis of Coffee Consumption and Risk of Prostate Cancer. Urol J. 2017; 14:4079-88.).

Prevention of PCa

In general, measures are very similar to those taken to prevent cardiovascular risks, such as increasing consumption of fruits and vegetables, while reducing red meats and saturated fats. A reduction in PCa incidence risk has been associated with high tomato and lycopene consumption, a phytochemical of the carotenoid family, with antioxidant properties (4343 Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst. 2002; 94:391-8., 4444 Etminan M, Takkouche B, Caamaño-Isorna F. The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies. Cancer Epidemiol Biomarkers Prev. 2004; 13:340-5.). The most recent meta-analysis on tomato consumption and PCa risk found that the increase in consumption is inversely associated with the risk of PCa (RR 0.81, 0.71-0.92), and a dose-response association was found (4545 Rowles JL 3rd, Ranard KM, Applegate CC, Jeon S, An R, Erdman JW Jr. Processed and raw tomato consumption and risk of prostate cancer: a systematic review and dose-response meta-analysis. Prostate Cancer Prostatic Dis. 2018; 21:319-36.).

An increased risk of PCa with high consumption of beef, milk, or animal fat has been documented (55 Ballon-Landa E, Parsons JK. Nutrition, physical activity, and lifestyle factors in prostate cancer prevention. Curr Opin Urol. 2018; 28:55-61.). More importantly, diet patterns seem to affect PCa progression. In this regard, people on predominantly Western diets (increased consumption of meats, processed products, and fats) have higher risk of PCa compared to those with high consumption of vegetables, fruits, and whole grains (1616 Fabiani R, Minelli L, Bertarelli G, Bacci S. A Western Dietary Pattern Increases Prostate Cancer Risk: A Systematic Review and Meta-Analysis. Nutrients. 2016; 8:626., 4646 Yang M, Kenfield SA, Van Blarigan EL, Batista JL, Sesso HD, Ma J, Stampfer MJ, et al. Dietary patterns after prostate cancer diagnosis in relation to disease-specific and total mortality. Cancer Prev Res (Phila). 2015; 8:545-51.). Meanwhile, the Mediterranean diet has encouraged the consumption of vegetables, fruits, nuts and seeds, whole grains, dairy products, olive oil, fresh fish, and seafood while restricting the intake of red and processed meats, fats, and sugary foods. A recent meta-analysis suggests that this dietary pattern is unrelated to overall PCa risk (RR 0.95 IC95% 0.90-1.01), or even cancer mortality (4747 Cheng S, Zheng Q, Ding G, Li G. Mediterranean dietary pattern and the risk of prostate cancer: A meta-analysis. Medicine (Baltimore). 2019; 98:e16341.). This diet and the so-called DASH have been inversely associated with the risk of aggressive PCa (4848 Schneider L, Su LJ, Arab L, Bensen JT, Farnan L, Fontham ETH, et al. Dietary patterns based on the Mediterranean diet and DASH diet are inversely associated with high aggressive prostate cancer in PCaP. Ann Epidemiol. 2019; 29:16-22.e1.).

Pascual-Geller et al. found that a high intake of nuts and fish offered a protective function. In addition, there was a significant risk reduction of PCa in cases with higher consumption of fruits and vegetables, in addition to a lower risk of aggressiveness associated with eating fruits, vegetables, legumes, and fish. Similarly, Alvarez-Cubero et al. found that fruit consumption was associated with a lower Gleason score (4949 Pascual-Geler M, Urquiza-Salvat N, Cozar JM, Robles-Fernandez I, Rivas A, Martinez-Gonzalez LJ, et al. The influence of nutritional factors on prostate cancer incidence and aggressiveness. Aging Male. 2018; 21:31-9., 5050 Alvarez-Cubero MJ, Pascual-Geler M, Rivas A, Martinez-Gonzalez LJ, Saiz M, Lorente JA, et al. Lifestyle and dietary factors in relation to prostate cancer risk. Int J Food Sci Nutr. 2015; 66:805-10.). Notwithstanding, vegetarianism has not shown a significant reduction in the risk of PCa (5151 Godos J, Bella F, Sciacca S, Galvano F, Grosso G. Vegetarianism and breast, colorectal and prostate cancer risk: an overview and meta-analysis of cohort studies. J Hum Nutr Diet. 2017; 30:349-59.).

Based on the involvement of inflammation in the pathogenesis of some tumors such as PCa, the impact of some dietary components has been studied. Thus, saturated fats, refined sugars, and red meats could have pro-inflammatory properties, while some soy and phytochemical products would have anti-inflammatory properties. An increase in the diet's inflammatory index did not show an increase in the risk of PCa (RR 1.06 IC95% 0.97-1.15) (5252 Jayedi A, Emadi A, Shab-Bidar S. Dietary Inflammatory Index and Site-Specific Cancer Risk: A Systematic Review and Dose-Response Meta-Analysis. Adv Nutr. 2018; 9:388-403.). In contrast, antioxidant intake has been associated with a decrease in some biomarkers of oxidative stress in urine and benign prostate tissue in patients with PCa (5353 Vance TM, Azabdaftari G, Pop EA, Lee SG, Su LJ, Fontham ET, et al. Intake of dietary antioxidants is inversely associated with biomarkers of oxidative stress among men with prostate cancer. Br J Nutr. 2016; 115:68-74.) (Supplementary material 2).

Exercise and Pca

Studies on exercise and PCa have sought to establish their association with a decrease in tumor progression and mortality, as well as benefits in quality of life, post-prostatectomy urinary incontinence, and bone quality in patients with metastases, among others. Epidemiological studies have associated exercise and physical activity, including regular long-term recreational or occupational physical activity, with a decrease in cancer risk, specifically PCa, between 10 and 30%. Also, among the benefits of implementing an exercise regimen, there are: 1) Induction of epigenetic modifications; 2) Improvement in quality of life; 3) Regulation of the inflammatory response and immune system, and 5) Improvement in body composition by increasing muscle tissue (5454 Campos C, Sotomayor P, Jerez D, González J, Schmidt CB, Schmidt K, et al. Exercise and prostate cancer: From basic science to clinical applications. Prostate. 2018; 78:639-45.5757 Sorial E, Si S, Fritschi L, Darcey E, Leavy JE, Girschik J, et al. Lifetime recreational physical activity and the risk of prostate cancer. Cancer Causes Control. 2019; 30:617-25.).

There seems to be a significant benefit in decreasing exercise-related oxidative stress, which lowers hydrogen peroxide levels, a free radical involved in carcinogenesis, and other inflammatory mediators, including TNF-a and IL-6 (55 Ballon-Landa E, Parsons JK. Nutrition, physical activity, and lifestyle factors in prostate cancer prevention. Curr Opin Urol. 2018; 28:55-61., 77 Thomas RJ, Kenfield SA, Jimenez A. Exercise-induced biochemical changes and their potential influence on cancer: a scientific review. Br J Sports Med. 2017; 51:640-4., 5858 Hayes BD, Brady L, Pollak M, Finn SP. Exercise and Prostate Cancer: Evidence and Proposed Mechanisms for Disease Modification. Cancer Epidemiol Biomarkers Prev. 2016; 25:1281-8.). It is also important to note that a decreased risk is usually more significant with vigorous exercise than with light physical activity, demonstrating a dose-response effect (5555 Shephard RJ. Physical Activity and Prostate Cancer: An Updated Review. Sports Med. 2017; 47:1055-73.). Multiple studies have shown a decrease in cancer-specific mortality associated with increased physical activity. On the other hand, Friedenreich et al. found a 38% reduction in PCa mortality in patients performing post-diagnostic physical activity (5959 Friedenreich CM, Neilson HK, Farris MS, Courneya KS. Physical Activity and Cancer Outcomes: A Precision Medicine Approach. Clin Cancer Res. 2016; 22:4766-75.). Also, prospective studies associate vigorous physical activity with decreased PCa mortality and reduced progression in patients with localized PCa (6060 Peisch SF, Van Blarigan EL, Chan JM, Stampfer MJ, Kenfield SA. Prostate cancer progression and mortality: a review of diet and lifestyle factors. World J Urol. 2017; 35:867-74.).

Although physical activity has been shown to be of moderate benefit for fatigue reduction, sub-maximum physical condition, lower hemibody strength, perception of masculinity, body image, cognitive and social function, no significant effect has been found on the quality of life of PCa patients, disease progression, sexual function or cardiovascular health (6161 Bourke L, Smith D, Steed L, Hooper R, Carter A, Catto J, et al. Exercise for Men with Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol. 2016; 69:693-703.6363 Langelier DM, D’Silva A, Shank J, Grant C, Bridel W, Culos-Reed SN. Exercise interventions and their effect on masculinity, body image, and personal identity in prostate cancer-A systematic qualitative review. Psychooncology. 2019; 28:1184-96.). In particular, endurance exercise improves muscle mass and strength in patients with PCa, without showing improvement in quality of life and fatigue. However, in patients treated with androgen deprivation therapy (ADT), there has been no difference between aerobic or resistance exercise (6464 Keilani M, Hasenoehrl T, Baumann L, Ristl R, Schwarz M, Marhold M, et al. Effects of resistance exercise in prostate cancer patients: a meta-analysis. Support Care Cancer. 2017; 25:2953-68., 6565 Yunfeng G, Weiyang H, Xueyang H, Yilong H, Xin G. Exercise overcome adverse effects among prostate cancer patients receiving androgen deprivation therapy: An update meta-analysis. Medicine (Baltimore). 2017; 96:e7368.). It should be noted that leisure time physical activity, such as walking, swimming, or dancing, has not been associated with a lower risk of local or advanced PCa (6666 Liu F, Wang J, Wu HL, Wang H, Wang JX, Zhou R, et al. Leisure time physical activity and risk of prostate cancer: a dose-response meta-analysis. Minerva Urol Nefrol. 2018; 70:152-61.). Also, synergistically, exercise can lead to an increase in the potency of chemotherapy or radiation therapy by increasing circulation and intratumor chemotherapy delivery. Even as neoadjuvant therapy, exercise may be adequate in preparing and improving physical tolerance of patients who are taken to first-line chemotherapy (6767 Hart NH, Galvão DA, Newton RU. Exercise medicine for advanced prostate cancer. Curr Opin Support Palliat Care. 2017; 11:247-57.). In patients taken to radical prostatectomy, pelvic floor exercises have shown to decrease the incidence of urinary incontinence significantly. However, these exercises do not appear to show any benefit when used only as a postoperative therapy (6868 Wu ML, Wang CS, Xiao Q, Peng CH, Zeng TY. The therapeutic effect of pelvic floor muscle exercise on urinary incontinence after radical prostatectomy: a meta-analysis. Asian J Androl. 2019; 21:170-6.).

Androgen deprivation therapy is generally considered a standard intervention in patients with locally advanced or metastatic PCa. However, it is associated with multiple adverse effects, such as reduction in muscle mass and strength, decrease in bone mass and density, in addition to increased fat mass, insulin resistance, fatigue, and alterations in sexual function (5454 Campos C, Sotomayor P, Jerez D, González J, Schmidt CB, Schmidt K, et al. Exercise and prostate cancer: From basic science to clinical applications. Prostate. 2018; 78:639-45.). It has been shown that exercise can significantly improve cancer-related fatigue and quality of life in patients treated with ADT, as well as increase strength in the upper and lower body, help maintain control of fat mass and Body Mass Index (BMI), maintain sexual function, and mitigate resistance to some medications (such as enzalutamide). However, it has no substantial evidence for improvement of depression, bone mineral density or other blood markers (6565 Yunfeng G, Weiyang H, Xueyang H, Yilong H, Xin G. Exercise overcome adverse effects among prostate cancer patients receiving androgen deprivation therapy: An update meta-analysis. Medicine (Baltimore). 2017; 96:e7368., 6767 Hart NH, Galvão DA, Newton RU. Exercise medicine for advanced prostate cancer. Curr Opin Support Palliat Care. 2017; 11:247-57., 6969 Yang B, Wang J. Effects of Exercise on Cancer-related Fatigue and Quality of Life in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Meta-analysis of Randomized Clinical Trials. Chin Med Sci J. 2017; 32:13-21., 7070 Ying M, Zhao R, Jiang D, Gu S, Li M. Lifestyle interventions to alleviate side effects on prostate cancer patients receiving androgen deprivation therapy: a meta-analysis. Jpn J Clin Oncol. 2018; 48:827-34.). Despite current evidence and recommendations on lifestyle interventions in PCa patients treated with ADT, patients continue to experience increased central adiposity, loss of bone density, and worsening of glycemia due to lack of adherence (7171 Owen PJ, Daly RM, Livingston PM, Fraser SF. Lifestyle guidelines for managing adverse effects on bone health and body composition in men treated with androgen deprivation therapy for prostate cancer: an update. Prostate Cancer Prostatic Dis. 2017; 20:137-45.).

Men with more vigorous long-term physical activity had a 30% lower risk of progression to advanced PCa, and a 25% lower risk of dying from PCa (7272 García-Gómez FJ, Riva-Pérez PA, Agudo-Martínez A, Sabatel-Hernández G, Calvo-Morón MC. Whole muscle 18F-choline uptake due to intense physical exercise. Int Braz J Urol. 2019; 45:851-2.). Also, muscle endurance exercises (non-aerobic) reduce the risk of tumor recurrence. It was also found that men with more robust physical activity had a lower risk of developing the TMPRSS2:ERG gene fusion (66 Pernar CH, Ebot EM, Pettersson A, Graff RE, Giunchi F, Ahearn TU, et al. A Prospective Study of the Association between Physical Activity and Risk of Prostate Cancer Defined by Clinical Features and TMPRSS2:ERG. Eur Urol. 2019; 76:33-40.).

Mental health and PCa

Prostate cancer is a challenge for the mental health of patients even before they are diagnosed because of all the implications and interventions around it. During diagnostic procedures, specifically prostate biopsy, symptoms of depression or anxiety may be mild; however, when the biopsy is negative, anxiety symptoms are more significant in those with post-biopsy complications (pain, bruising, hematospermia, among other symptoms) (7373 Wade J, Rosario DJ, Macefield RC, Avery KN, Salter CE, Goodwin ML, et al. Psychological impact of prostate biopsy: physical symptoms, anxiety, and depression. J Clin Oncol. 2013; 31:4235-41.). Screening with PSA has not been associated with increased concern or psychological distress. However, fear, anxiety, and lack of information can impact decisions and perceptions patients have about its performance (7474 Chad-Friedman E, Coleman S, Traeger LN, Pirl WF, Goldman R, Atlas SJ, et al. Psychological distress associated with cancer screening: A systematic review. Cancer. 2017; 123:3882-94., 7575 Ahiagba P, Alexis O, Worsley AJ. Factors influencing black men and their partners’ knowledge of prostate cancer screening: a literature review. Br J Nurs. 2017; 26:S14-S21.).

According to Watts et al., the prevalence of depression prior to, during, and after treatment for PCa was 17.27%, 14.7%, and 18.44%, respectively; while for anxiety, it was 27.04%, 15.09%, and 18.49%, respectively, both considerably high (7676 Watts S, Leydon G, Birch B, Prescott P, Lai L, Eardley S, et al. Depression and anxiety in prostate cancer: a systematic review and meta-analysis of prevalence rates. BMJ Open. 2014; 4:e003901.). Besides, mortality in patients with depression may be higher, and related emotional symptoms can negatively influence decision-making regarding therapy (7777 Squiers W. Outcomes for depressed patients with prostate cancer. Lancet Oncol. 2014; 15:e370., 7878 Prasad SM, Eggener SE, Lipsitz SR, Irwin MR, Ganz PA, Hu JC. Effect of depression on diagnosis, treatment, and mortality of men with clinically localized prostate cancer. J Clin Oncol. 2014; 32:2471-8.).

Central concepts that influence the well-being of PCa patients include a sense of purpose, social connection, and motivation in life, which are suggested as essential areas of focus in practice (7979 Levy A, Cartwright T. Men's strategies for preserving emotional well-being in advanced prostate cancer: An interpretative phenomenological analysis. Psychol Health. 2015; 30:1164-82.). In this respect, patients with depressive symptoms benefit significantly from peer support or psychotherapy (8080 Newby TA, Graff JN, Ganzini LK, McDonagh MS. Interventions that may reduce depressive symptoms among prostate cancer patients: a systematic review and meta-analysis. Psychooncology. 2015; 24:1686-93.). Although no clinical trials were found to evaluate the efficacy of antidepressant medications in PCa patients, population studies reveal their regular use (8181 Fervaha G, Izard JP, Tripp DA, Rajan S, Leong DP, Siemens DR. Depression and prostate cancer: A focused review for the clinician. Urol Oncol. 2019; 37:282-8.).

Patients with lower educational levels were found to be at increased risk of developing depressive symptoms, warranting relevant psychosocial interventions in high-risk groups (8282 Friberg AS, Rask Moustsen I, Benzon Larsen S, Hartung T, Wreford Andersen E, Halgren Olsen M, et al. Educational level and the risk of depression after prostate cancer. Acta Oncol. 2019; 58:722-9.). Furthermore, multidisciplinary interventions, such as online psychosocial support, can encourage that patients return to work, reducing the social and economic burden of PCa (8383 de Boer AG, Taskila TK, Tamminga SJ, Feuerstein M, Frings-Dresen MH, Verbeek JH. Interventions to enhance return-to-work for cancer patients. Cochrane Database Syst Rev. 2015; 2015:CD007569., 8484 Huntley A. Prostate cancer: Online support reduces distress in men with prostate cancer. Nat Rev Urol. 2016; 13:9-10.).

Active surveillance has helped patients with low-risk PCa avoid or postpone active treatment and prevent possible adverse effects; however, the impact it may have on the psychosocial well-being of patients has not been well documented (8585 Ruane-McAteer E, Porter S, O’Sullivan JM, Santin O, Prue G. Active surveillance for favorable-risk prostate cancer: Is there a greater psychological impact than previously thought? A systematic, mixed studies literature review. Psychooncology. 2017; 26:1411-21.).

In support care, some unmet needs that merit person-centered care are identified. These include intimacy, information, physical, and psychological needs (8686 Paterson C, Robertson A, Smith A, Nabi G. Identifying the unmet supportive care needs of men living with and beyond prostate cancer: A systematic review. Eur J Oncol Nurs. 2015; 19:405-18.). Although radical prostatectomy, active surveillance, and radiation therapy are well tolerated in terms of post-treatment anxiety and depression, sexual and intestinal dysfunction, and, above all, urinary incontinence, can induce worsening of psychological distress (8787 Maggi M, Gentilucci A, Salciccia S, Gatto A, Gentile V, Colarieti A, et al. Psychological impact of different primary treatments for prostate cancer: A critical analysis. Andrologia. 2019; 51:e13157.).

Research regarding the impact of circadian cycle disruption on the risk of PCa, such as sleep disorders, or night shift work, which has inconsistently shown an increased risk of PCa predominantly in Asian populations, has been expanded in recent years. The risk is higher in rotating night shift work over fixed ones (8888 Wendeu-Foyet MG, Menegaux F. Circadian Disruption and Prostate Cancer Risk: An Updated Review of Epidemiological Evidences. Cancer Epidemiol Biomarkers Prev. 2017; 26:985-91.9191 Mancio J, Leal C, Ferreira M, Norton P, Lunet N. Does the association of prostate cancer with night-shift work differ according to rotating vs. fixed schedule? A systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2018; 21:337-44.).

In addition to the adverse effects of ADT mentioned above, other psychological effects include, difficulties in multiple sexual domains, emotional lability, cognitive disturbances, reversible Parkinson's dementia, anxiety, and an increase in the risk for depression of up to 41%; these symptoms are significantly associated with alcohol consumption and smoking (9292 Abbate C, Caputo L, Damanti S, Zappa C, Nicolini P, Rossi PD, et al. Reversible Parkinson's Dementia Associated with Withdrawal of Androgen-Deprivation Therapy for Prostate Cancer. J Am Geriatr Soc. 2016; 64:e115-e117.9595 Nead KT, Sinha S, Yang DD, Nguyen PL. Association of androgen deprivation therapy and depression in the treatment of prostate cancer: A systematic review and meta-analysis. Urol Oncol. 2017; 35:664.e1-664.e9.). Similarly, couples can also suffer emotional consequences related to the effects of ADT, with exercise being a useful intervention for the dyad (9696 Donovan KA, Walker LM, Wassersug RJ, Thompson LM, Robinson JW. Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners. Cancer. 2015; 121:4286-99.). It has also been shown that the patient's partner may be afraid of recurrence of the disease, becoming a significant concern (9797 van de Wal M, Langenberg S, Gielissen M, Thewes B, van Oort I, Prins J. Fear of cancer recurrence: a significant concern among partners of prostate cancer survivors. Psychooncology. 2017; 26:2079-85.).

Multimodal treatment and PCa

Having a pro-inflammatory cellular environment is one of the most important mechanisms in carcinogenesis. The presence of oxidative stress, inflammatory cytokines, and accelerated cell growth leads to a stable medium that predisposes mutations and expression of carcinogenic phenotypes (4343 Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of tomato products, lycopene, and prostate cancer risk. J Natl Cancer Inst. 2002; 94:391-8., 9898 Silberstein JL, Parsons JK. Prostate cancer prevention: concepts and clinical recommendations. Prostate Cancer Prostatic Dis. 2010; 13:300-6.). Within the tertiary prevention of PCa, the MEAL study included 440 patients between the ages of 50 and 70, diagnosed with low-risk localized PCa (9999 Parsons JK, Pierce JP, Mohler J, Paskett E, Jung SH, Morris MJ, et al. Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]): recruitment feasibility and baseline demographics of a randomized trial of diet in men on active surveillance for prostate cancer. BJU Int. 2018; 121:534-9.). The progression of the disease was analyzed at the histological and biochemical level, in addition to the presence of urinary symptoms, a specific level of anxiety and quality of life (9999 Parsons JK, Pierce JP, Mohler J, Paskett E, Jung SH, Morris MJ, et al. Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]): recruitment feasibility and baseline demographics of a randomized trial of diet in men on active surveillance for prostate cancer. BJU Int. 2018; 121:534-9.); vegetables high in isothiocyanates, carotenes, and lycopene were found to be associated with PCa prevention (9898 Silberstein JL, Parsons JK. Prostate cancer prevention: concepts and clinical recommendations. Prostate Cancer Prostatic Dis. 2010; 13:300-6., 9999 Parsons JK, Pierce JP, Mohler J, Paskett E, Jung SH, Morris MJ, et al. Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]): recruitment feasibility and baseline demographics of a randomized trial of diet in men on active surveillance for prostate cancer. BJU Int. 2018; 121:534-9.). Macro and micronutrient levels were measured in plasma during fasting, and results were generalizable to the general population; there were no significant differences between the age groups (p=0.98), race (p=0.52), geographic distribution (p=0.60), time of diagnosis of PCa (p=0.85), PSA values (p=0.96), clinical stage (p=0.27), and Gleason stratification (p=0.76) (9999 Parsons JK, Pierce JP, Mohler J, Paskett E, Jung SH, Morris MJ, et al. Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]): recruitment feasibility and baseline demographics of a randomized trial of diet in men on active surveillance for prostate cancer. BJU Int. 2018; 121:534-9.).

It was concluded that a healthy lifestyle, a diet low in saturated fats, and increased consumption of vegetables (more than six in a day) and legumes, were linked to stable or lower PSA levels, and a decrease in disease progression.

At the molecular level, changes in cellular expression, increased telomerase activity, and a higher stability in its terminals have been evidenced. The rates of intervention and progression of the disease were decreased, inhibiting carcinogenesis mechanisms and inducing the expression of cytoprotective enzymes (9898 Silberstein JL, Parsons JK. Prostate cancer prevention: concepts and clinical recommendations. Prostate Cancer Prostatic Dis. 2010; 13:300-6., 9999 Parsons JK, Pierce JP, Mohler J, Paskett E, Jung SH, Morris MJ, et al. Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]): recruitment feasibility and baseline demographics of a randomized trial of diet in men on active surveillance for prostate cancer. BJU Int. 2018; 121:534-9.).

Patients with BMI >25 have increased levels of biomarkers linked to disease aggressiveness, such as C-peptide, insulin, insulin-like growth factor (IGF-1), IGF 3 binding protein, and adiponectin. They also have insulin receptor expression changes, IGF-1 receptor, and AKT receptor in epithelial and stromal cells, linked with rapid disease progression (7070 Ying M, Zhao R, Jiang D, Gu S, Li M. Lifestyle interventions to alleviate side effects on prostate cancer patients receiving androgen deprivation therapy: a meta-analysis. Jpn J Clin Oncol. 2018; 48:827-34., 100100 Schenk JM, Neuhouser ML, Beatty SJ, VanDoren M, Lin DW, Porter M, et al. Randomized trial evaluating the role of weight loss in overweight and obese men with early stage prostate Cancer on active surveillance: Rationale and design of the Prostate Cancer Active Lifestyle Study (PALS). Contemp Clin Trials. 2019; 81:34-9.). Free radical augmentation is generated from beta-oxidation during fat metabolism and induction of prostate inflammation, causing a significant increase in the risk of progression (101101 Kogevinas M, Espinosa A, Castelló A, Gómez-Acebo I, Guevara M, Martin V, et al. Effect of mistimed eating patterns on breast and prostate cancer risk (MCC-Spain Study). Int J Cancer. 2018; 143:2380-9.). Some authors propose inhibition of fatty acid synthase as a protective mechanism; however, documented studies are inconclusive (3333 Liu B, Mao Q, Cao M, Xie L. Cruciferous vegetables intake and risk of prostate cancer: a meta-analysis. Int J Urol. 2012; 19:134-41., 4242 Xia J, Chen J, Xue JX, Yang J, Wang ZJ. An Up-to-date Meta-analysis of Coffee Consumption and Risk of Prostate Cancer. Urol J. 2017; 14:4079-88., 5353 Vance TM, Azabdaftari G, Pop EA, Lee SG, Su LJ, Fontham ET, et al. Intake of dietary antioxidants is inversely associated with biomarkers of oxidative stress among men with prostate cancer. Br J Nutr. 2016; 115:68-74., 7171 Owen PJ, Daly RM, Livingston PM, Fraser SF. Lifestyle guidelines for managing adverse effects on bone health and body composition in men treated with androgen deprivation therapy for prostate cancer: an update. Prostate Cancer Prostatic Dis. 2017; 20:137-45.).

The active intervention of a plant-based diet, supplemented with soy, fish oil, vitamin E, selenium, and vitamin C, in conjunction with three hours per week of moderate exercise and one hour of daily stress management in support groups among patients with localized PCa, has shown slower carcinogenesis progression and decreased cell proliferation activity by approximately 70% (p <0.001). Satisfactory physical perception and lower levels of anxiety are reflected in quality of life assessment scales (102102 Frattaroli J, Weidner G, Dnistrian AM, Kemp C, Daubenmier JJ, Marlin RO, et al. Clinical events in prostate cancer lifestyle trial: results from two years of follow-up. Urology. 2008; 72:1319-23.).

Dietary recommendations for patients with localized or metastatic castration resistant PCa have been the same as those that seek to reduce the risk of developing PCa (103103 Ma RW, Chapman K. A systematic review of the effect of diet in prostate cancer prevention and treatment. J Hum Nutr Diet. 2009; 22:187-99; quiz 200-2.). However, it has been considered whether some dietary products may have interactions with drugs used to treat castration resistant PCa. Pharmacokinetic studies have shown that the dosage of abiraterone with high or low-fat meals is associated with a modest increase in drug concentration compared to the usual fasting dosage (104104 Chi KN, Spratlin J, Kollmannsberger C, North S, Pankras C, Gonzalez M, et al. Tran NP. Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer. J Clin Pharmacol. 2015; 55:1406-14.). Szmulewitz et al. found that administering this drug with a low fat breakfast had a similar effect in terms of PSA levels and progression-free survival (105105 Szmulewitz RZ, Peer CJ, Ibraheem A, Martinez E, Kozloff MF, Carthon B, et al. Prospective International Randomized Phase II Study of Low-Dose Abiraterone With Food Versus Standard Dose Abiraterone In Castration-Resistant Prostate Cancer. J Clin Oncol. 2018; 36:1389-95.).

Author's proposal

As noted above, the recommendations for lifestyle changes around PCa and its complications are not distant from the strategies for cardiovascular risk prevention. Currently, multiple molecular mechanisms appear to be involved in the development and progression of the disease, so even greater biological plausibility will be found to support these interventions.

As dietary measures, it is recommended to keep a low intake of simple carbohydrates, decrease consumption of red meats and processed foods, and reduce consumption of saturated fats. In addition, dietary patterns with high consumption of vegetables (predominantly cruciferous) and fruits, such as the Mediterranean diet, and high intake of tomatoes, may be suggested due to their lycopene content. Phytochemicals in tea and coffee are also beginning to play an essential role in the prevention of PCa and should be taken into account when guiding patients.

Muscular endurance exercise should be part of every doctor's general recommendations in the clinical field due to the potential benefit it confers in terms of cancer risk prevention and cardiovascular risk. These benefits are even more significant in patients diagnosed with PCa. Physical activity should be recommended throughout the disease process. It can improve patient's quality of life, urinary symptoms of incontinence, psychological stress resulting from the disease, and cancer-related fatigue until mortality is reduced; it also has the potential of being a significant neoadjuvant and adjuvant mode of therapy for the treatment of PCa. The introduction and promotion of multidisciplinary programs aimed at prevention, treatment, and palliation of PCa in Latin America are indispensable. A change in public policy is required to transform the reality of our patients.

These recommendations should be maintained for patients on ADT, in order to improve patient's quality of life. They may also be combating other mental health conditions, such as depression or anxiety, a widespread reality in these patients.

Priority is made to provide a comprehensive approach to PCa patients to influence all these factors and reduce the risk of progression. In this regard, the presence of anxious or depressive symptoms, tobacco use, or alcoholism should always be ruled out and alert to the presence of adverse psychosocial conditions that may worsen the prognosis and course of the disease. Psychosocial support should be included as part of standard management.

Establishing an adequate perception of the disease, while promoting protective factors, and educating patients on healthy lifestyles positively impacts the health system because of the decreased economic impact and greater adherence to treatment. Patients undergoing surgery, hormone therapy, and radiation therapy with joint monitoring of their lifestyle and risk factors may lower health costs and minimize the morbidity related to treatment (55 Ballon-Landa E, Parsons JK. Nutrition, physical activity, and lifestyle factors in prostate cancer prevention. Curr Opin Urol. 2018; 28:55-61., 5555 Shephard RJ. Physical Activity and Prostate Cancer: An Updated Review. Sports Med. 2017; 47:1055-73., 7070 Ying M, Zhao R, Jiang D, Gu S, Li M. Lifestyle interventions to alleviate side effects on prostate cancer patients receiving androgen deprivation therapy: a meta-analysis. Jpn J Clin Oncol. 2018; 48:827-34., 9999 Parsons JK, Pierce JP, Mohler J, Paskett E, Jung SH, Morris MJ, et al. Men's Eating and Living (MEAL) study (CALGB 70807 [Alliance]): recruitment feasibility and baseline demographics of a randomized trial of diet in men on active surveillance for prostate cancer. BJU Int. 2018; 121:534-9., 106106 Céspedes MS, Radtke JP, Cathelineau X, Sanchez-Salas R. Prostate specific membrane antigen (PSMA) and Prostate Cancer Staging: is our current conventional staging obsolete? Int Braz J Urol. 2021;47:1243-9.).

Figure 1 and Supplementary material 2 summarize the recommendations for intervening in the lifestyle of patients.

Figure 1
Summary outline of recommendations in healthy lifestyle.

CONCLUSIONS

Preventive interventions at all levels are the cornerstone of adherence to disease treatment and progression avoidance. The relationship in terms of healthy lifestyles is related to greater survival. The risk of developing cancer is associated to different eating habits, determined by geographic variations, possibly related to different genetic susceptibilities.

Screening for anxiety and the presence of symptoms related to mood disorders is essential in the patient's follow-up concerning their perception of the condition.

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APPENDIX

Supplementary material 1
Search strategies. We used MeSH terms and synonyms related to prostate cancer and the suggested interventions.
Supplementary material 2
Summary of recommendations on lifestyle changes and Pca

Publication Dates

  • Publication in this collection
    11 Mar 2022
  • Date of issue
    Mar-Apr 2022

History

  • Received
    16 Apr 2021
  • Accepted
    20 May 2021
  • Published
    15 Aug 2021
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