Effect of population trends in body mass index on prostate cancer incidence and mortality in the United States.

Concurrent with increasing prostate cancer incidence and declining prostate cancer mortality in the United States, the prevalence of obesity has been increasing steadily. Several studies have reported that obesity is associated with increased risk of high-grade prostate cancer and prostate cancer mortality, and it is thus likely that the increase in obesity has increased the burden of prostate cancer. In this study, we assess the potential effect of increasing obesity on prostate cancer incidence and mortality. We first estimate obesity-associated relative risks of low- and high-grade prostate cancer using data from the Prostate Cancer Prevention Trial. Then, using obesity prevalence data from the National Health and Nutrition Examination Survey and prostate cancer incidence data from the Surveillance, Epidemiology, and End Results program, we convert annual grade-specific prostate cancer incidence rates into incidence rates conditional on weight category. Next, we combine the conditional incidence rates with the 1980 prevalence rates for each weight category to project annual grade-specific incidence under 1980 obesity levels. We use a simulation model based on observed survival and mortality data to translate the effects of obesity trends on prostate cancer incidence into effects on disease-specific mortality. The predicted increase in obesity prevalence since 1980 increased high-grade prostate cancer incidence by 15.5% and prostate cancer mortality by between 7.0% (under identical survival for obese and nonobese cases) and 23.0% (under different survival for obese and nonobese cases) in 2002. We conclude that increasing obesity prevalence since 1980 has partially obscured declines in prostate cancer mortality

Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics

Background: Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer. Methodology/Principal Findings: Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer. Conclusions/Significance: Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy

Circulating Fatty Acids and Prostate Cancer Risk: Individual Participant Meta-Analysis of Prospective Studies

Background: Individual studies have suggested that some circulating fatty acids are associated with prostate cancer risk, but have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. Methods: Principal investigators of prospective studies on circulating fatty acids and prostate cancer were invited to collaborate. Investigators provided individual participant data on circulating fatty acids (weight percent) and other characteristics of prostate cancer cases and controls. Prostate cancer risk by study-specific fifths of 14 fatty acids was estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. Results: Five thousand and ninety-eight case patients and 6649 control patients from seven studies with an average follow-up of 5.1 (SD = 3.3) years were included. Stearic acid (18:0) was inversely associated with total prostate cancer (odds ratio [OR] Q5 vs Q1 = 0.88, 95% confidence interval [CI] = 0.78 to 1.00, P trend = .043). Prostate cancer risk was, respectively, 14% and 16% greater in the highest fifth of eicosapentaenoic acid (20:5n-3) (OR = 1.14, 95% CI = 1.01 to 1.29, P trend = .001) and docosapentaenoic acid (22:5n-3) (OR = 1.16, 95% CI = 1.02 to 1.33, P trend = .003), but in each case there was heterogeneity between studies (P = .022 and P < .001, respectively). There was heterogeneity in the association between docosapentaenoic acid and prostate cancer by grade of disease (P = .006); the association was statistically significant for low-grade disease but not high-grade disease. The remaining 11 fatty acids were not statistically associated with total prostate cancer risk. Conclusion: There was no strong evidence that circulating fatty acids are important predictors of prostate cancer risk. It is not clear whether the modest associations of stearic, eicosapentaenoic, and docosapentaenoic acid are causal

Economic Analysis of Prostate-Specific Antigen Screening and Selective Treatment Strategies.

ImportanceProstate-specific antigen (PSA) screening for prostate cancer is controversial. Experts have suggested more personalized or more conservative strategies to improve benefit-risk tradeoffs, but the value of these strategies-particularly when combined with increased conservative management for low-risk cases-is uncertain.ObjectivesTo evaluate the potential cost-effectiveness of plausible PSA screening strategies and to assess the value added by increased use of conservative management among low-risk, screen-detected cases.Design, setting, and participantsA microsimulation model of prostate cancer incidence and mortality was created. A simulated contemporary cohort of US men beginning at 40 years of age underwent 18 strategies for PSA screening. Treatment strategies included (1) contemporary treatment practices based on age and cancer stage and grade observed in the Surveillance, Epidemiology, and End Results program in 2010 or (2) selective treatment practices whereby cases with a Gleason score lower than 7 and clinical T2a stage cancer or lower are treated only after clinical progression, and all other cases undergo contemporary treatment practices. National and trial data on PSA growth, screening and biopsy patterns, incidence of prostate cancer, treatment distributions, treatment efficacy, mortality, health-related quality of life, and direct medical expenditure were analyzed. Data were collected from March 18, 2009, to August 15, 2014, and analyzed from November 20, 2012, to December 11, 2015.InterventionsEighteen screening strategies that vary by start and stop age, screening interval, and criteria for biopsy referral and contemporary or selective treatment practices.Main outcomes and measuresLife-years (LYs), quality-adjusted life-years (QALYs), direct medical expenditure, and cost per LY and QALY gained.ResultsAll 18 screening strategies were associated with increased LYs (range, 0.03-0.06) and costs ($263-$1371) compared with no screening, with the cost ranging from $7335 to$21 649 per LY. With contemporary treatment, only strategies with biopsy referral for PSA levels higher than 10.0 ng/mL or age-dependent thresholds were associated with increased QALYs (0.002-0.004), and only quadrennial screening of patients aged 55 to 69 years was potentially cost-effective in terms of cost per QALY (incremental cost-effectiveness ratio, $92 446). With selective treatment, all strategies were associated with increased QALYs (0.002-0.004), and several strategies were potentially cost-effective in terms of cost per QALY (incremental cost-effectiveness ratio,$70 831-$136 332).Conclusions and relevanceFor PSA screening to be cost-effective, it needs to be used conservatively and ideally in combination with a conservative management approach for low-risk disease

Limitations of basing screening policies on screening trials: The US Preventive Services Task Force and Prostate Cancer Screening.

BackgroundThe US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial.Objective: To examine limitations of basing screening policy on evidence from screening trials.MethodsWe reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results.ResultsScreening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial.ConclusionsModeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening-and more favorable harm-benefit tradeoffs-than has been suggested by empirical trial evidence