Risk Of Fatal Prostate Cancer Research Articles

Abstract 4801: Clinical polygenic model to stratify risk of any, metastatic, and fatal prostate cancer in a randomized controlled trial of precision screening

Abstract Introduction: Lifetime risk of prostate cancer (PCa) is strongly associated with three factors: ancestry, family history, and genetics. We previously developed a polygenic hazard score (PHS) for PCa comprised of 290 common genetic variants (PHS290). When accounting for family history and ancestry (self-reported or genetically determined), PHS290 remained a powerful independent predictor of age at PCa diagnosis, metastatic PCa diagnosis, and PCa death. Additional variants associated with PCa susceptibility or benign elevation of prostate-specific antigen (PSA) have since been published. Here, we evaluate their impact on lifetime risk predictions for metastatic and fatal PCa and develop an updated polygenic score. This score will inform the design of the Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS, ClinicalTrials.gov ID NCT05926102), a nationwide randomized controlled trial evaluating precision PCa screening in the VA healthcare system. Methods: We utilized a machine learning approach to update the PHS. Over 450 variants associated with PCa, aggressive PCa, benign prostatic hyperplasia, or benign PSA elevation were evaluated for inclusion. First, we identified pairs of variants with highly correlated genotype (defined as R2 > 0.95) and utilized univariable Cox proportional hazards models (using age at diagnosis of PCa) to exclude one variant from each pair. We then evaluated all remaining candidate variants for inclusion in a new PHS using a LASSO-regularized Cox proportional hazards model. We combined the new PHS with clinical predictors (ancestry and family history) to create a comprehensive, quantitative polygenic score in a diverse, population-based cohort of n=590,750 (Million Veteran Program). Both self-reported and genetic ancestry (based on 2,309 ancestry informative markers) were assessed. We estimated hazard ratios (HRs) to compare men with high versus low polygenic score and evaluated absolute predictions of any, metastatic, and fatal PCa. Results: The updated polygenic score included 356 variants, as well as family history and genetic ancestry. When comparing the highest to the lowest quintile of the population for polygenic score, the HRs for any PCa, metastatic PCa, and fatal PCa were 5.6, 5.8, and 5.2 respectively. These HRs are all greater than those achieved with PHS290, which yielded 5.2, 4.9, and 4.4 respectively. Risk stratification improved within each ancestry group, including within the >100,000 participants of African ancestry—a group known to have elevated risk of fatal PCa. Absolute risk prediction was accurate for both metastatic and fatal PCa. Conclusion: The polygenic score accurately predicts risk of metastatic and fatal PCa in multiple ancestry groups. A clinical polygenic model has potential utility for precision PCa screening and will now be evaluated prospectively in the ProGRESS trial. Citation Format: Anna M. Dornisch, Roshan Karunamuni, Kara N. Maxwell, Julie Lynch, Isla P. Garraway, Adam Kibel, Charles A. Brunette, Morgan E. Danowski, Kyung M. Lee, Scott L. DuVall, J M. Gaziano, Brent S. Rose, Richard L. Hauger, Jason L. Vassy, Tyler M. Seibert. Clinical polygenic model to stratify risk of any, metastatic, and fatal prostate cancer in a randomized controlled trial of precision screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4801.

Plant-based diet associated with better quality of life in prostate cancer survivors.

Plant-based diets have many health benefits, including a lower risk of fatal prostate cancer, and greater environmental sustainability. However, less is known regarding the impact of plant-based diets on quality of life among individuals diagnosed with prostate cancer. The authors' objective was to examine the relationship between plant-based diet indices postdiagnosis with quality of life. This prospective cohort study included 3505 participants in the Health Professionals Follow-Up Study (1986-2016) with nonmetastatic prostate cancer. Food-frequency questionnaires were used to calculate overall and healthful plant-based diet indices. Quality-of-life scores were calculated using the Expanded Prostate Cancer Index Composite. Generalized estimating equations were used to examine associations over time between plant-based diet indices and quality-of-life domains (sexual functioning, urinary irritation/obstruction, urinary incontinence, bowel functioning, hormonal/vitality), adjusted for demographics, oncologic history, body mass index, caloric intake, health-related behaviors, and comorbidities. The median age at prostate cancer diagnosis was 68years; 48% of patients underwent radical prostatectomy, and 35% received radiation as primary therapy. The median time from diagnosis/treatment to first the quality-of-life questionnaire was 7.0years. A higher plant-based diet index was associated with better scores for sexual function, urinary irritation/obstruction, urinary incontinence, and hormonal/vitality. Consuming more healthful plant-based foods was also associated with better sexual and bowel function, as well as urinary incontinence andhormonal/vitality scores in the age-adjusted analysis, but not in the multivariable analysis. This prospective study provides supportive evidence that greater consumption of healthful plant-based foods is associated with modestly higher scores in quality-of-life domains among patients with prostate cancer.

Abstract B028: Vigorous physical activity associated changes in immune cell infiltrate are linked with reduced prostate tumour aggressiveness

Abstract Vigorous physical activity has been associated with lower risk of fatal prostate cancer and improved cancer-specific outcomes. However, the mechanisms contributing to this relationship are not understood. The current study characterized inflammation in prostate cancer tissue and evaluated features of the immune microenvironment related to physical activity and prostate cancer aggressiveness. We studied 119 men with prostate cancer participating in the University of North Carolina Health Registry/Cancer Survivorship Cohort who underwent radical prostatectomy. Structured questionnaires were administered at patients' study entry to assess physical activity. Digital image analysis of H&E-stained tissue sections using QuPath was applied to quantify Tumour Infiltrating Lymphocytes (TILs) in glands and stroma of tumor and adjacent normal regions. Nanostring gene expression profiling was performed on tumour tissue and a 50-gene signature utilized to predict immune cell types. ERG gene expression was used as a surrogate of TMPRSS2:ERG fusion status. Logistic regression was used to test associations of inflammation features with tumour aggressiveness and recreational physical activity measures. Cox proportional hazards analysis was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between immune cell types and risk of prostate cancer progression, with validation in a separate study of 101 radiation-treated prostate cancer patients. Our study comprised 77% white and 23% black men, and 25% of men had Gleason grade ≥4+3, 29% men reported recreational vigorous activity prior to diagnosis of prostate cancer. Acute tumour inflammation affected 30% of men, while 53% showed acute inflammation of adjacent tissue. TILs were more abundant in glands than stroma; two-fold more in tumour and five-fold more in adjacent tissue. Frequency of inflammation was similar between ERG-positive and ERG-negative tumours. An inverse relationship was observed between recreational vigorous activity and TILs abundance. Expression of the immune gene signature was also significantly lower in men reporting any recreational vigorous activity compared to those reporting none (P=0.044), driven by reduced gene expression-predicted abundance of Th cells, exhausted CD8 T cells, macrophages and neutrophils. Moreover, T cells, Tfh, Treg, exhausted CD8 T cells and macrophages were significantly increased in men with Gleason grade ≥4+3 or clinical stage ≥III. Treg abundance was positively associated with prostate cancer progression (HR, 1.35; 95%CI 1.03-1.78) after adjusting for age and race, which was further strengthened in ERG-positive patients (HR, 1.60; 95%CI 1.03-2.47). We show that the immune landscape in prostate cancer is altered in men reporting vigorous physical activity. Immune cell types associated with an immunosuppressive microenvironment, including exhausted CD8 T cells, Tregs, and macrophages, may be potential candidate mechanisms linking recreational vigorous activity with reduced prostate tumour aggressiveness and improved outcomes. Citation Format: Lanshan Huang, Sophia Halliday, Linnea Olsson, Alina Hamilton, Erin Kirk, Laura Farnan, Adrian Gerstel, Stephanie Craig, Stephen Finn, Melissa Wilson, Melissa Troester, Eboneé Butler, Jeannette Bensen, Sara Wobker, Emma Allott. Vigorous physical activity associated changes in immune cell infiltrate are linked with reduced prostate tumour aggressiveness [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B028.

Association of plant-based diet index with quality of life in patients with prostate cancer.

5037 Background: Plant-based diets have many health benefits including a lower risk of fatal prostate cancer. Less is known about the relationship between diet and functional outcomes among prostate cancer survivors. We hypothesized that greater consumption of plant-based food after prostate cancer diagnosis is associated with improved quality of life (QOL). Methods: This prospective cohort study included 3,505 participants in the Health Professionals Follow-up Study with non-metastatic prostate cancer (1986-2016). Overall and healthful Plant-based Diet Indices were calculated from food frequency questionnaires with cumulative updating. QOL scores were calculated using the Expanded Prostate Cancer Index Composite. Generalized estimating equations were used to examine associations between Plant-based Diet Indices and 5 QOL domains, adjusted for clinical and demographic factors. Results: Higher Plant-Based Diet Index was associated with improved scores for sexual function, urinary irritation/obstruction, and urinary incontinence among men with prostate cancer. Consuming more healthful plant-based foods was also associated with better scores for bowel function and hormonal/vitality in the age-adjusted models. Results were similar in sensitivity analyses excluding patients with pre-existing erectile dysfunction or lower urinary tract symptoms, and adjusting for use of sexual or urinary medications. A limitation is that no participants followed a strict vegan diet. Conclusions: This prospective study suggests that greater consumption of healthful plant-based foods is associated with modest improvements in QOL domains among patients with prostate cancer. [Table: see text]

Total-, LDL-, and HDL-cholesterol, apolipoproteins, and triglycerides with risk of total and fatal prostate cancer in Black and White men in the ARIC study.

Cholesterol reduction is considered a mechanism through which cholesterol-lowering drugs including statins are associated with a reduced aggressive prostate cancer risk. While prior cohort studies found positive associations between total cholesterol and more advanced stage and grade in White men, whether associations for total cholesterol, low (LDL)- and high (HDL)-density lipoprotein cholesterol, apolipoprotein B (LDL particle) and A1 (HDL particle), and triglycerides are similar for fatal prostate cancer and in Black men, who experience a disproportionate burden of total and fatal prostate cancer, is unknown. We conducted a prospective study of 1553 Black and 5071 White cancer-free men attending visit 1 (1987-1989) of the Atherosclerosis Risk in Communities Study. A total of 885 incident prostate cancer cases were ascertained through 2015, and 128 prostate cancer deaths through 2018. We estimated multivariable-adjusted hazard ratios (HRs) of total and fatal prostate cancer per 1-standard deviation increments and for tertiles (T1-T3) of time-updated lipid biomarkers overall and in Black and White men. Greater total cholesterol concentration (HR per-1 SD = 1.25; 95% CI = 1.00-1.58) and LDL cholesterol (HR per-1 SD = 1.26; 95% CI = 0.99-1.60) were associated with higher fatal prostate cancer risk in White men only. Apolipoprotein B was nonlinearly associated with fatal prostate cancer overall (T2 vs. T1: HR = 1.66; 95% CI = 1.05-2.64) and in Black men (HR = 3.59; 95% CI = 1.53-8.40) but not White men (HR = 1.13; 95% CI = 0.65-1.97). Tests for interaction by race were not statistically significant. These findings may improve the understanding of lipid metabolism in prostate carcinogenesis by disease aggressiveness, and by race while emphasizing the importance of cholesterol control.

Association between Alcohol Intake and Prostate Cancer Mortality and Survival.

We conducted a systematic review and meta-analysis to investigate the role of alcohol consumption with the prognosis of prostate cancer (PCa). Published reports were gathered on 15 October 2022, from PUBMED/MEDLINE and EMBASE. We found 19 independent eligible studies on the association between consumption of alcoholic beverages and the risk of fatal PCa (n = 5), PCa mortality (n = 5) in healthy subjects, and PCa patients' survival (n = 7) or surrogates thereof (n = 2). We used random effects meta-analysis to obtain a summary risk estimate (SRE) and 95% confidence intervals (95%CI) for incidence of fatal PCa and PCa mortality. The meta-analysis revealed no association between alcohol consumption and fatal prostate cancer incidence risk in healthy subjects with an indication for publication bias, but omitting the study that mainly increased the between-study heterogeneity, the SRE becomes significant (SRE 1.33, 95%CI 1.12-1.58), and the heterogeneity disappeared (I2 = 0%) with no indication of publication bias. No association of alcohol consumption was found with mortality risk in PCa patients (SRE 0.97, 95%CI 0.92-1.03) and PCa mortality risk in healthy subjects (SRE 1.03, 95%CI 0.82-1.30). In conclusion, this study suggests that there is some evidence of an association between high alcohol consumption and an increased risk of incidence of fatal prostate cancer in healthy subjects. Given the inconsistencies this result warrants further confirmation.

Post-diagnostic health behaviour scores in relation to fatal prostate cancer

BackgroundIndividual health behaviours have been associated with fatal prostate cancer (PCa). Their combined association with fatal PCa after diagnosis is unknown.MethodsThis prospective cohort included 4518 men diagnosed with nonmetastatic PCa from the Health Professionals Follow-up Study. Exposures included a three-factor score integrating post-diagnostic fatal PCa risk factors (“2021 PCa Behaviour Score”), six-factor score integrating incident aggressive PCa risk factors (“2015 PCa Behaviour Score”), and two scores integrating recommendations for cancer prevention and survival, respectively. Multivariable Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for fatal PCa.ResultsOver a median 10.2 years, we observed 219 PCa deaths. Each additional point of one of the PCa-specific health behaviour scores (2015 PCa Behaviour Score) was associated with a 19% reduced fatal PCa risk (HR: 0.81, 95%CI: 0.68–0.97). The 2021 PCa Behaviour Score and scores integrating national recommendations were not associated with fatal PCa.ConclusionsWhile a PCa-specific health behaviour score was associated with a reduced risk of fatal PCa, we did not otherwise observe strong evidence of associations between post-diagnostic scores and fatal PCa. Avoiding tobacco, healthy body size, and physical activity may decrease PCa death risk, but further research is needed to inform cancer survivorship recommendations.

Abstract LB158: Total, LDL-, HDL-cholesterol, apolipoproteins, and triglycerides and risk fatal prostate cancer in black and white men in the ARIC study

Abstract Background: Cholesterol reduction is considered a mechanism through which lipid-lowering drugs including statins are associated with a reduced aggressive prostate cancer risk. While prior cohort studies found positive associations of total cholesterol with advanced stage and grade in White men based mostly on cholesterol at baseline, whether associations for total cholesterol, low (LDL)- and high (HDL)-density lipoprotein cholesterol, apolipoprotein B (LDL particle component) and A1 (HDL particle component), and triglycerides exist for fatal prostate cancer and in Black men using time-updated biomarkers is unknown. Methods: We conducted a prospective study of 1,553 Black and 5,071 White cancer-free men attending visit 1 (1987-1989) of the Atherosclerosis Risk in Communities Study. Death from prostate cancer was ascertained from the underlying cause on death certificates. Follow-up began at visit 1 and ended at date of death, loss to follow-up, or 12/31/2018, which ever came first. There were 128 deaths from prostate cancer (43 in Black men, 85 in White men) ascertained over 153,184 person years of follow-up (mean 23 years). We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for fatal prostate cancer per 1-standard deviation increment and for tertiles (T1-T3) of time-updated lipid biomarkers adjusting for baseline age, education, race and field center, and updated BMI, waist circumference, smoking status, hyperglycemia and diagnosed diabetes, aspirin use, and lipid-lowering drug use overall, and in Black and White men. Results: Higher total cholesterol concentration was associated with higher fatal prostate cancer risk in White men only (HR per-1 SD=1.25; 95%CI=1.00-1.58), and higher concentration of LDL cholesterol appeared to be associated with fatal prostate cancer in White men only (HR per-1 SD=1.26; 95%CI=0.99-1.60). Apolipoprotein B was non-linearly associated with fatal prostate cancer overall (T2 vs. T1 HR=1.66; 95% CI=1.05-2.64) and in Black men (T2 vs. T1 HR=3.59; 95% CI=1.53-8.40) but not in White men (T2 vs. T1 HR=1.13; 95% CI=0.65-1.97). HRs were >1 overall (T3 vs. T1 HR=1.18) and in Black men (T3 vs. T1 HR=2.11) but were not statistically significant. HDL-cholesterol, Apolipoprotein A1 and triglycerides were not associated with fatal prostate cancer overall and by race. Tests for statistical interaction by race were not statistically significant. Conclusion: Positive associations with fatal prostate cancer were observed with total and LDL-cholesterol in White men, and apolipoprotein B in Black men. These findings may improve the understanding of lipid metabolism in prostate carcinogenesis, and further emphasize the importance of cholesterol control. Support: NHLBI contracts, NCI grants, NPCR Citation Format: Michael T. Marrone, Anna E. Prizment, David Couper, Kenneth R. Butler, Brad C. Astor, Corinne E. Joshu, Elizabeth A. Platz, Alison M. Mondul. Total, LDL-, HDL-cholesterol, apolipoproteins, and triglycerides and risk fatal prostate cancer in black and white men in the ARIC study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB158.

Association of plant-based diet index with prostate cancer risk

Plant-based diets are associated with multiple health benefits and a favorable environmental impact. For prostate cancer, previous studies suggest a beneficial role of specific plant-based foods (e.g., tomatoes) and a potentially harmful role of specific animal-based foods (e.g., meat, dairy). However, less is known about plant-based dietary patterns. We sought to examine the relation between plant-based diet indices and prostate cancer risk, including clinically relevant disease. This was a prospective cohort study including 47,239 men in the Health Professionals Follow-Up Study (1986-2014). Overall and healthful plant-based diet indices were calculated from FFQs. Cox proportional hazards models were used to estimate HRs and 95% CIs to examine the risk of incident prostate cancer (total and by clinical category), among men ages <65 and ≥65 y. Of the 47,239 men, 6655 men were diagnosed with prostate cancer over follow-up, including 515 with advanced-stage disease at diagnosis, 956 with lethal disease (metastasis or death), and 806 prostate cancer deaths. Greater overall plant-based consumption was associated with a significantly lower risk of fatal prostate cancer (HR: 0.81; 95% CI: 0.64, 1.01; P-trend = 0.04). In men aged <65, a higher plant-based diet index was associated with a lower risk of advanced, lethal, and fatal prostate cancer. Moreover, greater consumption of a healthful plant-based diet was associated with lower risks of total (HR: 0.84; 95% CI: 0.73, 0.98; P-trend = 0.046) and lethal prostate cancer (HR: 0.56; 95% CI: 0.34, 0.94; P-trend = 0.03) at age <65. There were no associations between overall or healthful plant-based diet indices with prostate cancer among men ≥65 y. Fewer than 1% of participants followed a strict vegetarian or vegan diet. This prospective study provides supportive evidence that greater consumption of healthful plant-based foods is associated with a lower risk of aggressive forms of prostate cancer, with stronger benefit among men aged <65 y.

The Association of Prediagnostic Statin Use with Aggressive Prostate Cancer from the Multiethnic Cohort Study.

There is a growing body of evidence supporting the protective effect of statins on the risk of prostate cancer, in particular aggressive disease. Past research has mostly been conducted in North American cohorts of White men. In the multiethnic cohort (MEC), we investigated the association of prediagnostic statin use with the incidence and mortality of prostate cancer across five racial/ethnic groups (White, African American, Japanese American, Latino, and Native Hawaiian). Among 31,062 male participants who completed a detailed medication questionnaire, 31.4% reported use of statins, 2,748 developed prostate cancer, and 261 died from the disease. After adjusting for potential confounders, prediagnostic statin use was associated with a 32% lower risk of fatal prostate cancer [95% confidence interval (CI) = 0.50-0.91], with the inverse association suggested consistently across the five racial/ethnic groups. Moreover, an 11% lower risk of aggressive prostate cancer (95% CI = 0.76-1.03) was observed in statin users than in nonusers. We found no statistically significant association between prediagnostic statin use and total prostate cancer or nonaggressive disease. Prediagnostic statin use was suggestively associated with a 19% reduction in prostate cancer-specific mortality (95% CI = 0.59-1.10) and an 8% reduction in all-cause mortality (95% CI = 0.79-1.07). In the MEC, prediagnostic use of statin was associated with lower risks of aggressive forms of prostate cancer. Our findings provide further support for the potential benefits of statins in reducing the risk and mortality of prostate cancer, especially aggressive disease.

Drug use disorder and risk of incident and fatal prostate cancer among Swedish men: a nationwide epidemiological study

PurposeProstate cancer is the second most common cancer in men and a leading cause of cancer mortality worldwide. Men with drug use disorders (DUD) may potentially be at high risk for prostate cancer mortality because of delayed diagnosis and/or undertreatment. In this study, we aimed to investigate prostate cancer incidence, mortality, and stage at time of diagnosis among men with DUD compared to the general male population in Sweden.MethodsWe performed a follow-up study based on Swedish national register data for the period January 1997–December 2016. The study was based on 1,361,532 men aged 50–75 years at inclusion, of whom 9,259 were registered with DUD. Cox regression analysis was used to compute adjusted hazard ratios (HRs) for incident and fatal prostate cancer, and cancer stage at time of diagnosis, associated with DUD.ResultsDUD was associated with a slightly increased risk of incident prostate cancer (HR: 1.07, 95% confidence interval [CI] 1.00–1.14, p = 0.048) and substantially higher risk of fatal prostate cancer (HR: 1.59, 95% CI 1.40–1.82, p < 0.001), adjusted for age, socioeconomic factors, and comorbidities related to tobacco smoking and alcohol use disorder. No association was found between DUD and prostate cancer stage at diagnosis.ConclusionsMen with DUD have an increased risk of fatal prostate cancer, possibly related to undertreatment in this patient population. Our findings should raise attention among medical staff and decision-makers towards a disadvantaged group of men in need of easily accessible prostate cancer evaluation and treatment.

MP32-06 ASSOCIATION OF PLANT-BASED DIETARY PATTERNS WITH PROSTATE CANCER RISK

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II (MP32)1 Sep 2021MP32-06 ASSOCIATION OF PLANT-BASED DIETARY PATTERNS WITH PROSTATE CANCER RISK Stacy Loeb, Benjamin C. Fu, Scott R. Bauer, Claire H. Pernar, June M. Chan, Erin L. Van Blarigan, Edward L. Giovannucci, Stacey A. Kenfield, and Lorelei A. Mucci Stacy LoebStacy Loeb More articles by this author , Benjamin C. FuBenjamin C. Fu More articles by this author , Scott R. BauerScott R. Bauer More articles by this author , Claire H. PernarClaire H. Pernar More articles by this author , June M. ChanJune M. Chan More articles by this author , Erin L. Van BlariganErin L. Van Blarigan More articles by this author , Edward L. GiovannucciEdward L. Giovannucci More articles by this author , Stacey A. KenfieldStacey A. Kenfield More articles by this author , and Lorelei A. MucciLorelei A. Mucci More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002036.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Plant-based diets are associated with multiple health benefits as well as a favorable environmental impact. For prostate cancer, previous studies suggest a beneficial role of specific plant-based foods (e.g., tomatoes with lycopene) and a potentially harmful role of specific animal-based foods (e.g., meat and dairy). However, less is known about plant-based dietary patterns and prostate cancer risk. METHODS: This was a prospective study including 47,243 men followed for up to 28 years in the Health Professionals Follow-up Study. Plant-based dietary indices were calculated using data from food frequency questionnaires collected every four years. Cox proportional hazards models were used to calculate multivariable hazard ratios (HR) and 95% confidence intervals (CI) of the association between plant-based diet in relation to risk of incident prostate cancer. A priori we hypothesized that a plant-based diet would be associated with a lower risk of advanced, lethal and fatal cancers, and among men less than 65 years at diagnosis. RESULTS: A total of 6,660 men were diagnosed with prostate cancer over follow-up, including 516 with advanced stage at diagnosis, 958 with lethal disease and 807 deaths from prostate cancer. There was no association between the overall plant-based dietary index with total prostate cancer risk, although greater overall plant-based consumption was associated with a nonsignificant lower risk of fatal prostate cancer. In men age less than 65 at diagnosis, greater overall consumption of plant-based diet was associated with a lower risk of advanced prostate cancer (HR 0.68, 95% CI 0.42-1.10, p-trend=0.046). Moreover, among younger men, greater consumption of a healthful plant-based diet was associated with lower risks of total prostate cancer (HR 0.81; 95% CI 0.70-0.95, p-trend=0.01) and fatal disease (HR 0.53; 95% CI 0.32-0.90, p-trend=0.03). There were no associations with either the overall or healthful plant-based diet indices with prostate cancer among men older than 65 years. Limitations of the study include that <1% of the participants followed a strict vegetarian or vegan diet. CONCLUSIONS: In addition to well-established benefits for general health and the environment, data from this prospective study provide supportive evidence that greater consumption of healthful plant-based foods may be associated with a lower risk of total and fatal prostate cancer among younger men. Source of Funding: This work was supported by grants from the National Institutes of Health (U01 CA167552, T32 CA009001). SL and LAM are supported by the Prostate Cancer Foundation. SB is supported by grant 1K12DK111028 from the National Institute of Diabetes, Digestive, and Kidney Disorders © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e566-e567 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Stacy Loeb More articles by this author Benjamin C. Fu More articles by this author Scott R. Bauer More articles by this author Claire H. Pernar More articles by this author June M. Chan More articles by this author Erin L. Van Blarigan More articles by this author Edward L. Giovannucci More articles by this author Stacey A. Kenfield More articles by this author Lorelei A. Mucci More articles by this author Expand All Advertisement Loading ...

Selected Articles from This Issue

New technologies enabling multi-cancer early detection (MCED) may make “universal cancer screening” possible. To examine this possibility, Hubbell and colleagues modeled the results of an MCED test applied to a population representative of the Surveillance, Epidemiology and End Results (SEER) program. The model found the potential to intercep. 2 in 5 cancers before usual care, reducing late stage incidence by half, with the potential to reduce 1 in 4 cancer deaths due to this stage shift. This suggests that MCED tests added to usual care have the potential to substantially reduce overall cancer mortality.There is an ongoing debate regarding concomitant testing of cytology and HPV (co-testing) in comparison to stand-alone HPV testing for optimal screening of cervical cancer and its precursors. Liang and colleagues used population-based screening data from the German MARZY study to compare the accuracy of co-testing with stand-alone HPV testing using different cytology and HPV tests. Stand-alone HPV testing performed similarly to co-testing, with the latter strategy generating more false positive results and colposcopy referrals. Implementation of co-testing as a screening strategy translates to minor gains in screening detection at the cost of more harms than stand-alone HPV testing.Although the associations between obesity and risk of pancreatic cancer have been previously suggested, it is questionable whether this association is caused by metabolically unhealthy phenotype. Using the Korean National Health Insurance Service–Health Screening Cohort (NHIS-HEALS), this study by Chung and colleagues showed that the metabolically unhealthy normal weight (MUNW) and metabolically unhealthy obese (MUO) phenotypes had elevated risks of pancreatic cancer but the metabolically healthy obese (MHO) phenotyp. did not, compared to the metabolically healthy normal weight (MHNW) phenotype. Results suggest that metabolically unhealthy phenotype might represent a potential risk factor for pancreatic cancer occurrence independently of obesity.Studies reported that regular aspirin use associates with a reduced risk of fatal prostate cancer. Few included African American men. To close this knowledge gap, Tang and colleagues investigated the relationship of aspirin use with prostate cancer among African American men in the Southern Community Cohort Study, which prospectively recruited participants of predominately low-income backgrounds. The investigation showed that aspirin use was tentatively associated with a reduced prostate cancer mortality - but not with disease risk. The observation suggests that aspirin use should be further evaluated as an opportunity to decrease lethal prostate cancer in African American men.

Insulinemic and Inflammatory Dietary Patterns and Risk of Prostate Cancer

BackgroundHyperinsulinemia and inflammation are inter-related pathways that link diet with the risk of several chronic diseases. Evidence suggests that these pathways may also increase prostate cancer risk. ObjectiveTo determine whether hyperinsulinemic diet and inflammatory diet are associated with prostate cancer incidence and mortality. Design, setting, and participantsWe prospectively followed 41 209 men in the Health Professionals Follow-up Study (1986–2014). Scores for two validated dietary patterns were calculated from food frequency questionnaires at baseline and updated every 4 yr. Outcome measurements and statistical analysisTotal, advanced, and lethal prostate cancer outcomes were assessed. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were determined for associations between two empirical hypothesis-oriented dietary patterns—empirical dietary index for hyperinsulinemia and empirical dietary inflammatory pattern—and prostate cancer risk estimated using Cox proportional hazard regression. Results and limitationsDuring 28 yr of follow-up, 5929 incident cases of total prostate cancer, including 1019 advanced and 667 fatal, were documented. In multivariable-adjusted models, there was a 7% higher risk of advanced prostate cancer (HR: 1.07; 95% CI: 1.01–1.15) and a 9% higher risk of fatal prostate cancer (HR: 1.09; 95% CI: 1.00–1.18) per standard deviation (SD) increase in the hyperinsulinemic diet. When stratified by age, the hyperinsulinemic diet was associated with only earlier-onset aggressive prostate cancer (men under 65 yr), with per SD HRs of 1.20 (95% CI: 1.06–1.35) for advanced, 1.22 (1.04–1.42) for fatal, and 1.20 (1.04–1.38) for lethal. The inflammatory diet was not associated with prostate cancer risk in the overall study population, but was associated with earlier-onset lethal prostate cancer (per SD increase HR: 1.16; 95% CI: 1.00–1.35). ConclusionsHyperinsulinemia and inflammation may be potential mechanisms linking dietary patterns with the risk of aggressive prostate cancer, particularly earlier-onset disease. Patient summaryAvoiding inflammatory and hyperinsulinemic dietary patterns may be beneficial for the prevention of clinically relevant prostate cancer, especially among younger men.

Effect of obesity on the prognosis and recurrence of prostate cancer after radical prostatectomy: a meta-analysis.

BackgroundObesity has been found to be closely related to the increased risk of fatal prostate cancer (PCa), however there remains no evidence that further clarifies the relationship between obesity and the postoperative recurrence and poor prognosis of PCa. In this study, a systematic review and meta-analysis were performed to systematically evaluate the effect of obesity on the prognosis and recurrence of PCa after radical prostatectomy (RP).MethodsA literature search of the PubMed, Web of Science, and Embase databases was performed covering articles published between January 2013 and January 2020. Articles regarding the correlation between body mass index (BMI) and the prognosis and recurrence of PCa following RP were included in the meta-analysis. Two investigators independently screened the literature and extracted relevant data including publication information, key results, number of cancer cases, and multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software, and forest plots, funnel plots, and sensitivity analysis were also conducted.ResultsA total of 14 articles were included, all of which were analyzed for clinicopathological characteristics. Eight articles reported the biochemical recurrence (BCR) with prostate-specific antigen (PSA) as the predictor, and six articles reported the positive surgical margins (PSM). The meta-analysis showed that obese PCa patients had more postoperative recurrence and poor prognosis compared with the normal weight PCa patients, and the difference was statistically significant (OR =1.25, 95% CI: 1.10, 1.43). BCR exhibited no significant difference between obese and non-obese PCa patients after surgery (OR =1.2, 95% CI: 0.96, 1.46), and there were also no notable differences in PSM between the groups (OR =1.16, 95% CI: 0.99, 1.36). Subgroup analysis showed that obese PCa patients in the Americas (95% CI: 1.11, 1.37) and Europe (95% CI: 1.11, 1.78) were more likely to have surgical recurrence and poor prognosis (OR =1.40). Obese patients in the Americas were also more likely to have BCR after surgery (95% CI: 1.07, 1.36).ConclusionsObesity easily leads to poor prognosis and recurrence of PCa after RP.

Abstract 4648: Insulinemic and inflammatory dietary patterns and risk of prostate cancer

Abstract Background: Studies of diet and prostate cancer have primarily focused on individual dietary factors, often with null or mixed findings. Assessment of dietary patterns is an alternative approach and has been increasingly used in nutritional epidemiology, providing the advantage of better accounting for added effects and interactions of dietary components. Hyperinsulinemia and inflammation are interrelated biological pathways that link diet with risk of several cancers, and studies have suggested that these may also increase prostate cancer risk. Whether dietary patterns based on these pathways contribute to the development and progression of prostate cancer is unclear. Methods: We followed 39,776 men in the Health Professionals Follow-up Study (1986-2014) to examine associations between two empirical hypothesis-oriented dietary patterns with risk of total, local, advanced, and fatal prostate cancer. The two dietary patterns - empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) - were constructed using the weighted sum of food groups that predicted plasma C-peptide (EDIH) and inflammatory biomarkers (EDIP). Dietary scores were calculated from food frequency questionnaires at baseline and updated every 4 years. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Results: We documented 5,682 incident cases of total prostate cancer and 658 cases of fatal prostate cancer over 868,552 person-years of follow-up. In multivariable-adjusted models, men in the highest EDIH quintile had an 18% higher risk of advanced prostate cancer (HR: 1.18, 95% CI: 0.96-1.45; P=0.04 for trend) and a 24% higher risk of fatal prostate cancer (HR: 1.24, 95% CI: 0.96-1.59; P=0.03 for trend) compared to men in the lowest quintile. There were no significant associations for EDIP and prostate cancer risk. BMI did not modify the association for either dietary pattern. Conclusion: Hyperinsulinemia may be a potential mechanism linking dietary patterns and risk of aggressive prostate cancer. Additional studies to define mechanisms of action and interventions to reduce prostate cancer risk are warranted. Citation Format: Benjamin C. Fu, Fred K. Tabung, Claire H. Pernar, Weike Wang, Amparo G. Gonzalez-Feliciano, Ilkania M. Chowdhury-Paulino, Steven K. Clinton, Edmund Folefac, Mingyang Song, Adam S. Kibel, Edward L. Giovannucci, Lorelei A. Mucci. Insulinemic and inflammatory dietary patterns and risk of prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4648.

Intake of individual fatty acids and risk of prostate cancer in the European prospective investigation into cancer and nutrition.

The associations of individual dietary fatty acids with prostate cancer risk have not been examined comprehensively. We examined the prospective association of individual dietary fatty acids with prostate cancer risk overall, by tumor subtypes, and prostate cancer death. 142,239 men from the European Prospective Investigation into Cancer and Nutrition who were free from cancer at recruitment were included. Dietary intakes of individual fatty acids were estimated using center‐specific validated dietary questionnaires at baseline and calibrated with 24‐h recalls. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow‐up of 13.9 years, 7,036 prostate cancer cases and 936 prostate cancer deaths were ascertained. Intakes of individual fatty acids were not related to overall prostate cancer risk. There was evidence of heterogeneity in the association of some short chain saturated fatty acids with prostate cancer risk by tumor stage (p heterogeneity < 0.015), with a positive association with risk of advanced stage disease for butyric acid (4:0; HR1SD = 1.08; 95%CI = 1.01–1.15; p‐trend = 0.026). There were no associations with fatal prostate cancer, with the exception of a slightly higher risk for those who consumed more eicosenoic acid (22:1n‐9c; HR1SD = 1.05; 1.00–1.11; p‐trend = 0.048) and eicosapentaenoic acid (20:5n‐3c; HR1SD = 1.07; 1.00–1.14; p‐trend = 0.045). There was no evidence that dietary intakes of individual fatty acids were associated with overall prostate cancer risk. However, a higher intake of butyric acid might be associated with a higher risk of advanced, whereas intakes of eicosenoic and eicosapentaenoic acids might be positively associated with fatal prostate cancer risk.

Hyperglycemia, Classified with Multiple Biomarkers Simultaneously in Men without Diabetes, and Risk of Fatal Prostate Cancer.

The association between hyperglycemia and prostate cancer risk is inconsistent, and its association with prostate cancer mortality is understudied. Thus, we investigated the association between hyperglycemia and prostate cancer risk and mortality using multiple biomarkers simultaneously to classify hyper- and normoglycemia. We conducted a prospective analysis of 5,162 cancer-free men attending visit 2 (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study followed for total (N = 671) and lethal (N = 69) prostate cancer incidence and prostate cancer mortality (N = 64) through 2012. Men without diagnosed diabetes were classified as normo- or hyperglycemic using joint categories of fasting glucose, glycated hemoglobin, and glycated albumin (or fructosamine) defined by clinical or research cutpoints. We evaluated the multivariable-adjusted association of hyperglycemia with prostate cancer incidence and mortality using Cox proportional hazards regression; men with diagnosed diabetes were included as a separate exposure category. Among 4,753 men without diagnosed diabetes, 61.5% were classified as having hyperglycemia (high on ≥1 biomarker). HbA1c and glycated albumin together classified 61.9% of 1,736 men with normal fasting glucose as normoglycemic. Compared with men who were normal on all three biomarkers, men who were high on ≥1 biomarker had an increased risk of lethal [HR, 2.50; 95% confidence interval (CI), 1.12-5.58] and fatal (HR, 3.20; 95% CI, 1.26-8.48) disease, but not total prostate cancer incidence (HR, 0.98; 95% CI, 0.81-1.20); associations were similar including fructosamine instead of glycated albumin. Our findings indicate hyperglycemia is associated with an increased risk of lethal and fatal prostate cancer, but not total prostate cancer incidence.

Body mass index trajectories across adulthood and smoking in relation to prostate cancer risks: the NIH-AARP Diet and Health Study.

Previously we showed that adulthood body mass index (BMI) trajectories that result in obesity were associated with elevated risks of fatal prostate cancer (PCA). To further explore this relationship, we conducted a study within the NIH-AARP Diet and Health Study. Among 153730 eligible men enrolled in the NIH-AARP cohort from 1995 to 1996 (median follow-up = 15.1 years), we identified 630 fatal PCA cases and 16896 incident cases. BMI was assessed for ages 18, 35 and 50 and at study entry, enabling examination of latent class-identified BMI trajectories. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. BMI at study entry (mean age = 63, HR = 1.12; 95% CI = 1.01, 1.24, per 5-unit increase) and maximum BMI during adulthood (HR = 1.12; 95% CI = 1.02, 1.24, per 5-unit increase) shared modest associations with increased risk of fatal PCA. Smoking status likely modified the relationship between BMI trajectories and fatal PCA (Pinteraction = 0.035 via change-in-estimate variable section, P = 0.065 via full a priori model). Among never-smokers, BMI trajectory of normal weight to obesity was associated with increased risk of fatal disease (HR = 2.37; 95% CI = 1.38, 4.09), compared with the maintained normal weight trajectory, whereas there was no association among former or current-smokers. Total and non-aggressive PCA exhibited modest inverse associations with BMI at all ages, whereas no association was observed for aggressive PCA. Increased BMI was positively associated with fatal PCA, especially among never-smokers. Future studies that examine PCA survival will provide additional insight as to whether these associations are the result of biology or confounding.

Abstract 3224: Prospective serum metabolomic profiling of fatal prostate cancer

Abstract Metabolic dysregulation may play a role in the etiology of fatal prostate cancer, yet the association with pre-diagnostic serum metabolites has not been elucidated. We conducted a prospective serum metabolomic analysis of fatal prostate cancer risk in 523 cases and 523 matched controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Median time from baseline fasting serum collection to prostate cancer death was 18 years (interdecile range 10-26 years). We profiled 860 known metabolites through an ultrahigh-performance LC-MS/MS platform, and conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals of risk associated with 1-standard deviation increases in the log-metabolite signals. Based on a false discovery rate (FDR) of 0.15 or lower, 34 metabolites are identified as being associated with fatal prostate cancer. Notably, increased serum thioproline and the three cysteine-related amino acids combined (thioproline, cysteine and cystine) are associated with lower odds of fatal disease (OR=0.75 and 0.71, respectively; P≤8.2×10-5). In contrast, the serum dipeptide leucylglycine (OR=1.36, P=8.2×10-5), and three gamma-glutamyl amino acids, including gamma-glutamylvaline, gamma-glutamylglycine and gamma-glutamylleucine (OR=1.28-1.30, P≤4.6×10-4), are associated with increased fatal disease risk. Several other dipeptides including histidylalanine, valylglycine and leucylglutamine, as well as the nucleotides dihydroorotate, pseudouridine, 2'-O-methyluridine, 5,6-dihydrouridine and 5-methyluridine (ribothymidine), also have significant positive associations with fatal disease risk. Findings are not materially altered by adjustment for body mass index, smoking, serum total and HDL cholesterol, serum alpha-tocopherol and retinol, or the ATBC trial supplementation. Our results are also similar across strata of time from blood collection to prostate cancer death and age at blood collection. Gene-set analysis (GSA) reveals a significant peptide super-metabolic pathway association with lethal disease (P&amp;lt;0.0001), and the sub-pathways of dipeptides, pyrimidines (uracil containing), gamma-glutamyl amino acids, glycine/serine/threonine, n3 and n6 polyunsaturated fatty acids, amino-sugars, androgenic steroids, dicarboxylate fatty acids, and endocannabinoids are similarly associated with fatal prostate cancer (FDRs ≤ 0.1). Our study demonstrates a serum risk profile up to two decades prior to death of prostate cancer that is characterized by multiple dysregulated biochemical metabolites of redox status and dipeptide, pyrimidine (uracil), and gamma-glutamyl amino acid metabolism. The findings represent novel leads related to the molecular basis of the etiology or subclinical course of fatal prostate cancer that warrant examination in other populations. Citation Format: Jiaqi Huang, Alison M. Mondul, Stephanie J. Weinstein, Andriy Derkach, Steven C. Moore, Joshua N. Sampson, Demetrius Albanes. Prospective serum metabolomic profiling of fatal prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3224.