Quantifying the hidden burden of metastatic prostate cancer.

There is controversy about the benefit of prostate-specific antigen (PSA) screening. Prostate-specific antigen screening rates have decreased since 2008 in the US, and the incidence of metastatic prostate cancer has increased. However, there is no direct epidemiologic evidence of a correlation between population PSA screening rates and subsequent metastatic prostate cancer rates. To assess whether facility-level variation in PSA screening rates is associated with subsequent facility-level metastatic prostate cancer incidence. This retrospective cohort used data for all men aged 40 years or older with an encounter at 128 facilities in the US Veterans Health Administration (VHA) from January 1, 2005, to December 31, 2019. Yearly facility-level PSA screening rates, defined as the proportion of men aged 40 years or older with a PSA test in each year, and long-term nonscreening rates, defined as the proportion of men aged 40 years or older without a PSA test in the prior 3 years, from January 1, 2005, to December 31, 2014. The main outcomes were facility-level yearly counts of incident metastatic prostate cancer diagnoses and age-adjusted yearly metastatic prostate cancer incidence rates (per 100 000 men) 5 years after each PSA screening exposure year. The cohort included 4 678 412 men in 2005 and 5 371 701 men in 2019. Prostate-specific antigen screening rates decreased from 47.2% in 2005 to 37.0% in 2019, and metastatic prostate cancer incidence increased from 5.2 per 100 000 men in 2005 to 7.9 per 100 000 men in 2019. Higher facility-level PSA screening rates were associated with lower metastatic prostate cancer incidence 5 years later (incidence rate ratio [IRR], 0.91 per 10% increase in PSA screening rate; 95% CI, 0.87-0.96; P < .001). Higher long-term nonscreening rates were associated with higher metastatic prostate cancer incidence 5 years later (IRR, 1.11 per 10% increase in long-term nonscreening rate; 95% CI, 1.03-1.19; P = .01). From 2005 to 2019, PSA screening rates decreased in the national VHA system. Facilities with higher PSA screening rates had lower subsequent rates of metastatic prostate cancer. These data may be used to inform shared decision-making about the potential benefits of PSA screening among men who wish to reduce their risk of metastatic prostate cancer.

Among the estimated 230,000 men diagnosed with prostate cancer in the US each year there has been a rise in the number of radical prostatectomies (RP). There is some debate over the value of immediate adjuvant therapy following RP in men with high-risk pathological features versus delayed salvage radiation therapy when signs of disease progression are observed. Thus, it would be potentially useful to inform post-RP management strategies by more clearly identifying those patients at higher risk of progression and death from prostate cancer. A 22 gene-expression assay, Decipher® (GenomeDx Biosciences), has been developed in men treated with radical prostatectomy to predict the five-year risk of metastatic prostate cancer. Published and unpublished literature was evaluated to determine the analytic validity, clinical validity and clinical utility of Decipher. Limited information is available on the analytic validity of Decipher. In both discovery and validation studies, Decipher was shown to have good performance in discriminating men with metastasis from men without metastasis five years after surgery (AUC 0.75 to 0.90). In terms of clinical utility, no evidence was found reporting improved outcomes (lower prostate cancer specific mortality and treatment related adverse effects) from using this test to guide post-operative treatment. Four studies provided weak indirect evidence of clinical utility in which 31% to 43% of post-operative treatment recommendations were changed in men with high-risk prostate cancer based on test results, with 27% to 52% of treatment recommendations changing from any treatment to no treatment.

Appendectomy is a common surgical procedure to treat appendicitis. Limited studies have examined its association with prostate cancer, with one large cohort study suggesting a significantly increased risk of overall and advanced prostate cancer, especially among younger men. A total of 49,104 men in the Health Professionals Follow-up Study were followed from 1986 to 2016. Cox proportional hazards models were applied to evaluate the association between self-reported history of appendectomy and risk of overall and subtype-specific prostate cancer, adjusted for multiple risk factors. During 30 years of follow-up, we documented 7,253 overall prostate cancer cases, including 579 advanced and 1,092 lethal events. Compared to men without appendectomy, those who reported at baseline having had appendectomy were not at higher risk of overall [HR, 1.01; 95% confidence interval (CI), 0.95-1.07], advanced (HR, 0.99; 95% CI, 0.81-1.23), or lethal (HR, 1.04; 95% CI, 0.89-1.20) prostate cancer. The association remained null when stratified by age. We found no evidence of an association between appendectomy and the risk of overall and clinically important prostate cancer. We showed that appendectomy was not associated with overall or advanced prostate cancer after adjusting for multiple risk factors in a large population of men with 30 years of follow-up.

Introduction: This ecological model traces the etiology of a certain class of metastatic cancers, which kills Blacks at more than twice the rate of Whites. These malignancies, defined by the uncontrolled proliferation of TRPV6 mRNA in mutagenic tissue, include metastatic prostate cancer, triple-negative breast cancer, and colorectal and ovarian cancer. This study will show that the cause is an ethnic-specific haplotype of the TRPV6 calcium ion channel. This proto-oncogenic African TRPV6a variant is more calcium absorbent than the non-African/European TRPV6b allele. African-Americans inherited strong bones from their low-calcium-consuming (200-400 mg/day) Niger-Kordofanian West African ancestors. However, American Blacks are maladapted to the high-calcium food environment of the U.S. This research shows that the ancestral TRPV6a allele can become invasively oncogenic when overexposed to free calcium ions, leading to the aforementioned class of cancers. Methods: Analyses of the incidence of TRPV6-expressing cancers in Blacks and Whites as a function of dietary consumption are conducted. Results: These data show a direct correlation between levels of calcium intake in Blacks, who carry the ancestral TRPV6a calcium ion channel, and incidence of the following hormonal cancers: metastatic prostate cancer, triple-negative breast cancer, colorectal cancer and ovarian cancer. Summary: Because the African TRPV6a calcium ion channel variant is more absorbent of free calcium ions than its non-African counterpart, this ecological model shows that carriers of this variant are at increased risk of metastatic prostate cancer, triple-negative breast cancer, and ovarian and colorectal cancers, when exposed to high-calcium food environments. Conclusions: Hypersensitivity to Ca2+ triggers certain metastatic cancers in Blacks, characterized by the upregulation of TRPV6 transcript. Lidocaine and SOR-C-13, a peptide derived from the saliva of the short-tail shrew, are identified as potential TRPV6 calcium channel inhibitors. Citation Format: Constance B. Hilliard. Ecological model links proto-oncogene to high susceptibility of Blacks to TRPV6-expressing metastatic cancers [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B069.

Background Recent evidence suggests a role for inflammation in the etiology of prostate cancer. Cytokines are important regulators of immune response, including in cancer. In the context of cancer, Th1 cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and, to some extent, interleukin (IL)-6, can elicit immune reactions to tumor cells. IL-1β, IL-8, IL-10, and IL-12p70 may suppress immune response to a tumor. Immune profile may be an important prognostic factor for disease-free survival in cancer patients. Whether the circulating cytokine profile influences prostate cancer incidence is understudied. Thus, we evaluated the cytokine-prostate cancer association prospectively. Methods We conducted an age-race matched case-control study (268 pairs) of inflammatory cytokines (IFN-γ, IL-10, IL-12-p70, IL-1β, IL-6, IL-8, and TNF-α), measured using the ultrasensitive Meso Scale Discovery (MSD) platform, and incident prostate cancer in CLUE II. Cases were identified by cancer registry linkage. The odds ratio (OR) and 95% confidence interval (95% CI) of prostate cancer by quartile of cytokine was calculated using matched and multivariable-adjusted conditional logistic regression. Results Median concentrations of IFN-γ (p=0.002), TNF-α (p=0.04), and IL-6 (p=0.06) were lower in cases than controls. Concentrations of the other cytokines did not differ by case status. The multivariable-adjusted OR of prostate cancer decreased across quartiles of IFN-γ (p-trend=0.004), TNF-α (p-trend=0.03), and IL-6 (p-trend=0.005). After their mutual adjustment, the patterns of association remained the same. Of note, the highest (vs lowest) quartile of TNF-α (p=0.03) and IL-6 (p=0.001) was associated with lower risk of metastatic prostate cancer with high Gleason sum ≥7. Overall prostate cancer risk did not change across quartiles of the other cytokines, including IL-10, a Th2 cytokine. However, in normal weight men, higher IL-10 concentration was inversely associated with prostate cancer (highest vs lowest quartiles: OR=0.36; 95% CI: 0.19-0.68), whereas in overweight and obese men, IL-10 was not inversely associated with risk (OR=1.32; 95% CI: 0.87-1.97; p-interaction=0.001). Significant interactions with BMI were not observed for the other cytokines. Conclusion Men with a prediagnostic circulating cytokine profile indicative of Th1 immune response may have a lower risk of prostate cancer, including aggressive disease. Whether this circulating cytokine profile reflects 1) the intraprostatic immune environment in benign tissue that protects against the development of prostate cancer, 2) the immune milieu in response to a yet undetected prostate adenocarcinoma that inhibits its growth and thus detectability, and/or 3) a systemic immune profile that mediates the influence of modifiable factors on prostate cancer risk, warrants additional study. The IL-10-obesity interaction also warrants further study. Citation Format: Nrupen A. Bhavsar, Jay J. Bream, Alan K. Meeker, Charles G. Drake, Sarah B. Peskoe, Angelo M. De Marzo, William B. Isaacs, Elizabeth A. Platz. Peripheral cytokine profiles and prostate cancer risk in CLUE II. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3618. doi:10.1158/1538-7445.AM2013-3618

To the Editor: A recent study by Hongyi Zhang et al. reveals that patients with non-alcoholic fatty liver disease (NAFLD) typically exhibit an elevated risk of biochemical recurrence in patients with metastatic prostate cancer. Utilizing computed tomography (CT) scans, the research estimated liver fat levels and employed Cox models to examine the association between NAFLD and biochemical recurrence, while accounting for variables such as body mass index, adipose tissue, hypertension, and diabetes it was determined that NAFLD functions as an autonomous risk factor for biochemical recurrence in individuals with advanced-grade metastatic prostate cancer [1]. This study signifies the urgent need for new methods to accurately diagnose and treat NAFLD to lower the recurrence of metastatic prostate cancer. Artificial intelligence (AI) has emerged as a promising tool in NAFLD detection, as demonstrated by a systematic review of 25 studies showing AI-enhanced ultrasonography achieved an impressive sensitivity of 0.97 and specificity of 0.98, surpassing AI-assisted clinical databases. Likewise, the incorporation of AI in clinical datasets exhibited notable levels of sensitivity and specificity in identifying NASH and diagnosing liver fibrosis stages F1–F4. Overall, AI-driven systems show considerable promise in improving diagnostic precision for individuals with NAFLD, NASH, and liver fibrosis [2]. Liver biopsy is still the most effective method for the diagnosis of NAFLD; however, it is an invasive process that comes with the potential for serious complications like pain, infection, and bleeding, so it is not feasible for all suspected persons. Conversely, ultrasound assessment represents a noninvasive and convenient method widely employed in the clinical evaluation of NAFLD; nonetheless, the diagnostic accuracy may be affected by various factors, notably the subjective judgment of the examiner. Recent studies [3] have incorporated biomarkers such as adiponectin and caspase-cleaved cytokeratin 18 fragment (M30) into predictive models for NAFLD activity score (NAS). These models exhibit potential in monitoring disease progression, fluctuations in body mass, and differentiation between NASH and NAFLD, demonstrating an AUROC range of 0.70–0.73. Although many studies demonstrate elevated diagnostic efficacy, the practical deployment of these findings within clinical settings is still nascent. Furthermore, while AI significantly augments histological and imaging-based evaluations of NAFLD, its capacity to forecast long-term clinical outcomes—including its interaction with the progression of prostate cancer—necessitates validation through rigorously designed prospective trials. Presently, initiatives such as the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) consortium [4] and the Non-Invasive Biomarkers of Metabolic Liver Disease (NIMBLE) project [5] are scrutinizing noninvasive indicators, including AI-augmented imaging techniques, for the detection and progression monitoring of NAFLD. Additional research is imperative to evaluate whether the incorporation of AI into established prostate cancer screening protocols can enhance risk stratification and inform treatment strategies. Moreover, the variability of AI methodologies across different studies raises significant concerns regarding reproducibility and generalizability, thereby necessitating the establishment of standardized validation frameworks. By leveraging AI-driven diagnostic models, we can potentially bridge the gap between NAFLD and metastatic prostate cancer recurrence, enabling earlier identification of high-risk patients and personalized treatment strategies. Considering the emerging role of NAFLD as an autonomous risk factor for biochemical recurrence, the incorporation of AI-augmented hepatic evaluations into oncological protocols may enhance prognostic precision and therapeutic decision-making for individuals with prostate cancer. Subsequent investigations ought to prioritize the validation of AI's predictive efficacy across heterogeneous populations, as well as the examination of its potential in alleviating NAFLD-associated cancer progression. Addressing these deficiencies will be paramount in transitioning AI from a potentially transformative innovation into a clinically essential instrument for optimizing outcomes in both hepatic and oncological disease management. The authors declare no conflicts of interest. No new data were generated for this research.

Epidemiological evidence on dietary fat intake and advanced prostate cancer (PCa) risk is limited and inconclusive; moreover, no prospective study has been conducted to investigate the association between fat quality and quantity and advanced and lethal PCa risk. This prospective cohort included 49 424 men from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The fat quality index (FQI) and low-fat diet score (LFDs) were used to evaluate the quality and quantity separately, where higher scores indicated greater adherence. Cox proportional hazards regression was used to evaluate the risk of PCa incidence and mortality. Subgroup analyses were conducted to identify potential confounders. Sensitivity analyses were performed to assess the robustness of the results. During follow-up, a total of 857 incident cases of advanced PCa, including 425 lethal PCa were documented. Individuals in the highest compared with the lowest quartiles of FQI had a lower advanced PCa [hazard ratioQ4 versus Q1 : 0.72, 95% confidence interval (CI): 0.58-0.88, P for trend = 0.002] and lethal PCa (hazard ratioQ4 versus Q1 : 0.65, 95% CI: 0.48-0.87, P for trend = 0.005). This inverse association between FQI and advanced PCa risk was not observed for nonlethal PCa. Subgroup analyses indicated this inverse association of FQI with advanced PCa was only observed in participants with higher LFDs. No significant associations were found between LFDs and the risk of advanced and lethal PCa. Our findings suggest focusing on higher quality, rather than restricting the quantity of fat intake, may be an effective approach to reduce the risk of advanced PCa in the US population, particularly for lethal PCa.

324 Background: Androgen deprivation therapy (ADT) remains a standard of care in the treatment of locally advanced prostate cancer. But thanks to a few key trials (STAMPEDE, CHAARTED, and LATITUDE) reported within the past three years, docetaxel and abiraterone now have roles in extending overall survival in a patient population traditionally treated with ADT alone. These treatments when combined with ADT have been shown to extend overall survival in metastatic hormone-sensitive prostate cancer patients. The role of ADT in relation to other therapies continues to evolve rapidly. We intend to revisit ADT’s longstanding role in prostate cancer treatment using a national cancer database. Our aim is to look beyond traditional standards of care to identify patients more likely to have overall survival benefit from ADT. Are there any subgroups of patients with intermediate or high risk disease that have improved survival outcomes with androgen deprivation therapy, besides patients with localized disease that underwent radiation? Could there be other variables besides PSA and localization of the prostate cancer that should be considered when identifying ADT treatment candidates, or identifying survival trends in these groups? Methods: We are currently analyzing variables present in the National Cancer Database to retrospectively identify predictive factors for overall survival and progression to metastatic castrate resistant prostate cancer in locally advanced prostate cancers treated with ADT. We will evaluate time-to-death from the initiation of ADT and from the diagnosis of metastatic castrate resistant prostate cancer. The following variables in localized, locally advanced, and metastatic prostate cancer will be analyzed with Statistical Analysis Software: age, locally advanced, site-specific metastasis (M1a, M1b, M1c), Gleason score, local treatment (radical prostatectomy or radiation), stage (T, N, and M), prostate lobe (one vs. both; T2a/b vs. T2c), chemotherapy (date, time from M1 stage), comorbidity score, ethnicity, facility type, insurance, and risk groups (low/intermediate/high as per NCCN guidelines).

Prostate cancer is the most common non-cutaneous cancer and second leading cause of cancer death among men in the U.S. Although ecologic and migrant studies suggest that diet plays a role in the etiology of prostate cancer, few specific nutrients that alter its occurrence have been identified in case-control and cohort studies. Phytoestrogens are a family of bioactive compounds that are abundant in soy products and some other food groups (e.g. legumes and chick peas). Experimental studies revealed that phytoestrogen intake may modulate the risk of prostate cancer due to their structural similarity to 17β-estradiol and the resulting competitive binding to estrogen receptors. Despite biological plausibility, it still remains elusive whether phytoestrogen intake influences prostate cancer risk in human populations. Therefore, the objective of the present study was to investigate the associations between dietary intake of phytoestrogens and the risk of total and advanced prostate cancer among 30,097 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). A total of 3628 cases of prostate cancer (including 396 advanced cases) have been documented during a median follow up of 11.5 years. Advanced prostate cancer were defined as stage II cancer with a Gleason score of ≥8, or stage III or stage IV cancer. Dietary intake of phytoestrogens was assessed with a validated food frequency questionnaire. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for dietary intake of phytoestrogens in relation to prostate cancer risk. After adjustment for confounders, an increased risk of advanced prostate cancer was found for the higher dietary intake of isoflavones (HR: 1.58; 95% CI: 1.11, 2.24), genistein (HR: 1.42; 95% CI: 1.02, 1.98), daidzein (HR: 1.62; 95% CI: 1.13, 2.32), and glycitein (HR: 1.53; 95% CI: 1.09, 2.15). Conversely, it appears that the higher dietary intake of genistein was associated with a reduced risk of non-advanced prostate cancer (HR: 0.88; 95% CI: 0.78, 0.99) and total prostate cancer (HR: 0.90; 95% CI: 0.81, 1.00). The risk estimates presented above were obtained for comparisons between the quintile 5 and quintile 1 of respective phytoestrogen intake. In summary, our analysis of this national prospective cohort study suggests that dietary intake of phytoestrogens modulated the risk of prostate cancer and that some of these effects may differ by the aggressiveness of the disease. Citation Format: Michael Reger, Terrell Zollinger, Ziyue Liu, Josette Jones, Jianjun Zhang. Dietary intake of phytoestrogens and the risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1884. doi:10.1158/1538-7445.AM2015-1884

&lt;div&gt;AbstractBackground:&lt;p&gt;Appendectomy is a common surgical procedure to treat appendicitis. Limited studies have examined its association with prostate cancer, with one large cohort study suggesting a significantly increased risk of overall and advanced prostate cancer, especially among younger men.&lt;/p&gt;Methods:&lt;p&gt;A total of 49,104 men in the Health Professionals Follow-up Study were followed from 1986 to 2016. Cox proportional hazards models were applied to evaluate the association between self-reported history of appendectomy and risk of overall and subtype-specific prostate cancer, adjusted for multiple risk factors.&lt;/p&gt;Results:&lt;p&gt;During 30 years of follow-up, we documented 7,253 overall prostate cancer cases, including 579 advanced and 1,092 lethal events. Compared to men without appendectomy, those who reported at baseline having had appendectomy were not at higher risk of overall [HR, 1.01; 95% confidence interval (CI), 0.95–1.07], advanced (HR, 0.99; 95% CI, 0.81–1.23), or lethal (HR, 1.04; 95% CI, 0.89–1.20) prostate cancer. The association remained null when stratified by age.&lt;/p&gt;Conclusions:&lt;p&gt;We found no evidence of an association between appendectomy and the risk of overall and clinically important prostate cancer.&lt;/p&gt;Impact:&lt;p&gt;We showed that appendectomy was not associated with overall or advanced prostate cancer after adjusting for multiple risk factors in a large population of men with 30 years of follow-up.&lt;/p&gt;&lt;/div&gt;

&lt;div&gt;AbstractBackground:&lt;p&gt;Appendectomy is a common surgical procedure to treat appendicitis. Limited studies have examined its association with prostate cancer, with one large cohort study suggesting a significantly increased risk of overall and advanced prostate cancer, especially among younger men.&lt;/p&gt;Methods:&lt;p&gt;A total of 49,104 men in the Health Professionals Follow-up Study were followed from 1986 to 2016. Cox proportional hazards models were applied to evaluate the association between self-reported history of appendectomy and risk of overall and subtype-specific prostate cancer, adjusted for multiple risk factors.&lt;/p&gt;Results:&lt;p&gt;During 30 years of follow-up, we documented 7,253 overall prostate cancer cases, including 579 advanced and 1,092 lethal events. Compared to men without appendectomy, those who reported at baseline having had appendectomy were not at higher risk of overall [HR, 1.01; 95% confidence interval (CI), 0.95–1.07], advanced (HR, 0.99; 95% CI, 0.81–1.23), or lethal (HR, 1.04; 95% CI, 0.89–1.20) prostate cancer. The association remained null when stratified by age.&lt;/p&gt;Conclusions:&lt;p&gt;We found no evidence of an association between appendectomy and the risk of overall and clinically important prostate cancer.&lt;/p&gt;Impact:&lt;p&gt;We showed that appendectomy was not associated with overall or advanced prostate cancer after adjusting for multiple risk factors in a large population of men with 30 years of follow-up.&lt;/p&gt;&lt;/div&gt;

BackgroundProstate cancer is the most heritable cancer. There is a need to identify possible modifiable factors for men at an increased risk of prostate cancer due to genetic factors. ObjectiveTo examine whether men at an increased genetic risk of prostate cancer can offset their risk of disease or disease progression by adhering to a healthy lifestyle. Design, setting, and participantsWe prospectively followed 12 411 genotyped men in the Health Professionals Follow-up Study (1993–2019) and the Physicians’ Health Study (1983–2010). Genetic risk of prostate cancer was quantified using a polygenic risk score (PRS). A healthy lifestyle was defined by healthy weight, vigorous physical activity, not smoking, and a healthy diet. Outcome measurements and statistical analysisOverall and lethal prostate cancer events (metastatic disease/prostate cancer–specific death) were analyzed using time-to-event analyses estimating hazard ratios (HRs) and lifetime risks. Results and limitationsDuring 27 yr of follow-up, 3005 overall prostate cancer and 435 lethal prostate cancer events were observed. The PRS enabled risk stratification not only for overall prostate cancer, but also for lethal disease with a four-fold difference between men in the highest and lowest quartiles (HR, 4.32; 95% confidence interval [CI], 3.16–5.89). Among men in the highest PRS quartile, adhering to a healthy lifestyle was associated with a decreased rate of lethal prostate cancer (HR, 0.55; 95% CI, 0.36–0.86) compared with having an unhealthy lifestyle, translating to a lifetime risk of 1.6% (95% CI, 0.8–3.1%) among the healthy and 5.3% (95% CI, 3.6–7.8%) among the unhealthy. Adhering to a healthy lifestyle was not associated with a decreased risk of overall prostate cancer. ConclusionsOur findings suggest that a genetic predisposition for prostate cancer is not deterministic for a poor cancer outcome. Maintaining a healthy lifestyle may provide a way to offset the genetic risk of lethal prostate cancer. Patient summaryThis study examined whether the genetic risk of prostate cancer can be attenuated by a healthy lifestyle including a healthy weight, regular exercise, not smoking, and a healthy diet. We observed that adherence to a healthy lifestyle reduced the risk of metastatic disease and prostate cancer death among men at the highest genetic risk. We conclude that men at a high genetic risk of prostate cancer may benefit from adhering to a healthy lifestyle.

The aim of the present study was to examine the association between intake of folate, and specific folate vitamers, and the risk of advanced and total prostate cancer. The association between dietary folate and prostate cancer risk was evaluated in The Netherlands Cohort Study (NLCS) on diet and cancer, conducted among 58,279 men ages 55-69 years at baseline. Information on diet was collected at baseline by means of food frequency questionnaires. Incident cases were identified by record linkage with regional cancer registries and the Dutch National Database of Pathology Reports. After 17.3 years of follow-up, 3,669 incident prostate cancer cases, of which 1,290 advanced cases, and 2,336 male subcohort members were available for case-cohort analyses. Dietary folate was not associated with prostate cancer risk, nor with the risk of advanced prostate cancer, among men in the NLCS cohort (HR = 1.05, 95 % CI: 0.87-1.26 and HR = 1.09, 95 % CI: 0.88-1.35, respectively, for the highest quintile of folate intake vs. the lowest quintile). Specific folate vitamers were neither associated with the risk of prostate cancer or risk of advanced prostate cancer. Our results do not support an association of dietary folate or specific folate vitamers on the risk of prostate cancer, or advanced prostate cancer.

Sleep deficiency is a major public health problem. There are limited human data on whether sleep duration or disruption are risk factors for prostate cancer. We prospectively followed 32,141 men in the Health Professionals Follow-Up Study who reported their typical sleep duration in 1987, 2000, and 2008. We identified 4,261 incident prostate cancer cases, including 563 lethal cases through 2010. Sleep disruption was assessed in 2004 among 19,639 men, with 930 prostate cancer cases (50 lethal) identified from 2004 to 2010. Cox proportional hazards models were used to evaluate the association between sleep insufficiency and risk of overall and lethal prostate cancer. In 1987, 2% of men reported sleeping ≤5 hours per night. We found no association between habitual sleep duration or change in sleep duration with the risk of advanced or lethal prostate cancer. We also found no association between waking up during the night, difficulty falling asleep, or waking up too early, and risk of prostate cancer. In 2004, 6% of men reported never feeling rested when they woke up; these men had an increased risk of developing lethal prostate cancer compared with those who reported always feeling rested when they woke up (RR, 3.05; 95% CI, 1.15-8.10). We found no consistent association between self-reported sleep duration or sleep disruption and any of our prostate cancer outcomes. We did not find support for a consistent association between self-reported sleep and risk of advanced or lethal prostate cancer in this large cohort of men.

Prostate-specific antigen (PSA) testing provides significant benefits by reducing prostate cancer mortality, but also leads to important harms by detecting clinically insignificant cancers. Hence, there are urgent needs for complementary tools for middle-aged men with modest PSA elevations in blood. This review includes research on prostate cancer biomarkers in blood published from March 2013 through August 2014. Research progress has been made mainly on PSA as a predictive marker and in the field of kallikrein-based tests: [-2] proPSA, the prostate health index, and a panel of four kallikrein markers. As men with PSA levels below age-median are at very low 20-year risk of metastatic prostate cancer, individualized screening intervals, based on PSA levels, may help in reducing screening costs, prostate biopsies, and detection of insignificant cancer. Statistical models based on kallikrein-markers in blood improve the specificity at modestly elevated PSA (2-10 ng/ml), eliminate unnecessary biopsies, and help selecting men at risk of significant prostate cancer for biopsy or imaging. Individualized, risk-adapted PSA testing intervals and reflex-testing of kallikrein-markers for men with modestly increased PSA values may decrease the harms of screening. However, the clinical value of the proposed testing algorithms and additional tests awaits definitive confirmation in prospective trials.