Increase In Incidence Of Prostate Cancer Research Articles

Abstract A091: County-level analysis of the link between historical slavery and prostate cancer incidence

Abstract Background: Black individuals with prostate cancer in the US experience the widest racial disparity in both cancer incidence and mortality when compared to the average population. These differences are driven by the intersection of race and a wide range of structural and social determinants of health and equity. Structural and social inequities can drive disproportionate and adverse exposure to violence, poverty, and physical and emotional stress—among other exposures—which may impact biologic risk, health behaviors, and healthcare access. We hypothesize that the impacts of these structural and social determinants are rooted in historical events that continue to inform present day prostate cancer events and outcomes. Methods: This is an ecological study assessing county-level data from 13 states in the Southeastern US. Data on prostate cancer incidence and mortality (NCI: 2018), population estimates (CDC: 2015-2019), structural and social determinants (AHRQ: 2018), and the percentage enslaved individuals (NHGIS: 1860) were obtained. County data were linked across datasets using federal identifiers. Our primary exposure was the legacy of US slavery represented by the percentage of enslaved individuals by county. Random variables such as water access and rail transport (NHGIS: 1860) were used as controls. Variable selection for our multivariable model was informed by a directed acyclical graph that defined the causal relationship between historical slavery and present-day prostate cancer outcomes. Our primary dependent variable was prostate cancer counts per 100,000. We utilized Poisson log-linear regression models to estimate the difference in cancer counts by 10% increase of slave population by county (NHGIS: 1860). Results: Our data included over 3000 counties. In our fully adjusted model, a 10% increase in county slave population was associated with a 1.5% increase in prostate cancer incidence (p<0.001). In this same model, Black race, and age (> 50 years) were associated with a 77% and over 300% increase in cancer incidence (p<0.001). Among Black men, every 10% increase in county slave population was associated with a 1.1% increase in cancer incidence (p < 0.05). Among White men, every 10% increase in county slave population was associated with a 1.5% increase in cancer incidence (p<0.0001). Our adjusted models demonstrated significant increased associations between prostate cancer incidence and education, access to food, segregation index, and social vulnerability index. Conclusions: Our results indicate that a history of slavery is significantly associated with increased county-level prostate cancer incidence for all men in the US, irrespective of their race/ethnicity. The effect of historic slavery persists even after adjusting for present day structural/social determinants of equity and health. These findings demonstrate the importance in acknowledging and incorporating historical inequities and context in evaluating present days inequities in prostate cancer risk, care, and outcomes. Citation Format: Maheetha C. Bharadwaj, Sarah C. Holt, Hari Iyer, John Gore, Tim Rebbeck, Yaw Nyame. County-level analysis of the link between historical slavery and prostate cancer incidence [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A091.

Assessing the Potential of Small Peptides for Altering Expression Levels of the Iron-Regulatory Genes FTH1 and TFRC and Enhancing Androgen Receptor Inhibitor Activity in In Vitro Prostate Cancer Models.

Recent research highlights the key role of iron dyshomeostasis in the pathogenesis of prostate cancer (PCa). PCa cells are heavily dependent on bioavailable iron, which frequently results in the reprogramming of iron uptake and storage pathways. Although advanced-stage PCa is currently incurable, bioactive peptides capable of modulating key iron-regulatory genes may constitute a means of exploiting a metabolic adaptation necessary for tumor growth. Recent annual increases in PCa incidence have been reported, highlighting the urgent need for novel treatments. We examined the ability of LNCaP, PC3, VCaP, and VCaP-EnzR cells to form colonies in the presence of androgen receptor inhibitors (ARI) and a series of iron-gene modulating oligopeptides (FT-001-FT-008). The viability of colonies following treatment was determined with clonogenic assays, and the expression levels of FTH1 (ferritin heavy chain 1) and TFRC (transferrin receptor) were determined with quantitative polymerase chain reaction (PCR). Peptides and ARIs combined significantly reduced PCa cell growth across all phenotypes, of which two peptides were the most effective. Colony growth suppression generally correlated with the magnitude of concurrent increases in FTH1 and decreases in TFRC expression for all cells. The results of this study provide preliminary insight into a novel approach at targeting iron dysmetabolism and sensitizing PCa cells to established cancer treatments.

Abstract A017: The geospatial analysis of the socioeconomic status and its impact on prostate cancer prevalence in Alabama

Abstract Background: This study aims to understand the impact of Socioeconomic status (SES) and how it influences the aging population, increasing the risk of many diseases, including prostate cancer. The cancer prevalence in Alabama is high; prostate cancer rates are particularly high in the diverse male populations. Alabama's Black Belt rural counties are closely associated with socioeconomic and health disparities, and political oppression, among which social equity and socioeconomic status have been closely associated with prostate cancer incidence. This study explores prostate cancer occurrence in the aging population in the major ethnic groups (African American and Whites) in the State of Alabama, mainly in the black belt of Alabama. Prior studies have revealed that prostate cancer prevalence is related to biological, environmental, and socioeconomic characteristics. A precise sense of the root causes of the age-related increase in prostate cancer incidence is required to develop a strategy for building primary spatial and non-spatial cancer data using machine-learning tools. Hypothesis/Objectives: We hypothesized that SES might impact prostate cancer occurrence among the aging population. Our study aims to explore the impact of SES factors to understand prostate cancer incidence in the aging population in Alabama. Methods: We utilized Geospatial Technology (GT) to analyze the connection between aging and prostate cancer prevalence in different ethnic populations in Alabama. This study incorporated county-level prostate cancer prevalence and association with aging, SES, and health disparities. The robust data mining (Alabama Department of Senior Services, Alabama State Cancer Profile data, Alabama Department of Health, American Cancer Society, Center for Disease Control, and National Cancer Institute) enabled us to explore the association between aging and prostate cancer in the spatial context. Integrating spatial and non-spatial data on prostate cancer prevalence to SES will help predict and formulate prostate cancer prevention methods. Results: The GT's secondary data analysis revealed that prostate cancer affects minority communities in the Black Belt in Alabama. The GT analysis further demonstrates that this disparity is due to a lack of access to health care and mitigation efforts. The diverse data integration reveals that the SES and related factors modulate the aging population and prostate cancer occurrence. Conclusions: The preliminary finding demonstrates that SES is an essential factor that modulates prostate cancer incidences in underserved minority aging populations in Alabama. Hence, understanding the association between aging and socioeconomic disparities will help predict and prevent prostate cancer more effectively. Citation Format: Manoj K. Mishra, Seela Aladuwaka, Ram Alagan. The geospatial analysis of the socioeconomic status and its impact on prostate cancer prevalence in Alabama [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A017.

РАДИАЦИОННЫЕ РИСКИ РАКА ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ СРЕДИ ЛИКВИДАТОРОВ ПОСЛЕДСТВИЙ НА ЧАЭС (ПЕРИОД НАБЛЮДЕНИЯ 1996–2018 гг.)

Purpose: The paper deals with the occurrence of prostate cancer and mean survival time following a diagnosis of the disease among Chernobyl clean-up workers. Material and methods: Clinical and dosimetry data accumulated at the National Radiation and Epidemiological Registry (NRER) during the period from 1996 over 2018 were used for the study. The study cohort consisted of 69,698 men. During the follow-up 742 prostate cancer cases were detected, all patients had radiation dose records, the disease stage was established in 628 patients. To assess radiation risk maximum likelihood approach was used. Mean survival time was evaluated with the use of the relationship between a disease prevalence and newly detected disease cases intensity in a stationary population (diseases intensity is equal to intensity of mortality from all causes). Results: Excess relative risk of prostate cancer induction per 1 Gy was 0.74 (95 % CI: ‒0.31; 2.15) and it was statistically insignificant. Standardized incidence ratios between clean-up workers and male population of Russia within 95 % confidence limits do not differ from 1.0. Mean survival time after the disease diagnosis within the period from 1996 over 2018 was 3.5±1.3 years. The relationship between a survival time and a disease stage was estimated. Survival time for cases with 1–3 stages 3.3±2.9, 3.6±2.3, 4.3±2.7 years respectively. The less survival time for cases with stage 4 was 1.5±0.8 years. Mean mortality rate, i.e. the ratio of the number of clean-up workers died from prostate cancer to the total number of clean-up workers with diagnosed prostate cancer was 36.8 %, for stages 1–4 it was 20, 16, 37, 74 % respectively. Mean survival time in the groups with doses less than and higher than 150 mGy was 3.4±1.4 and 3.7±1.7, respectively. Presented data confirm the null hypothesis that there is no difference in survival times (p=0.20). Conclusion: Increase in prostate cancer incidence becomes the social problem not only in Russia but in other countries as well. The paper presents results of comprehensive radiation epidemiological analysis of prostate cancer incidence in cleanup workers, who constitute the representative sample of the Russian male population. The dose ‒ prostate cancer incidence relationship for the follow-up period from 1996 over 2018 is not statistically significant, although the value of excess relative risk per dose unit is positive. It is not unthinkable that the absence of statistical significance is caused due to limited length of the follow-up period. But at the same time, the fact that observed the standardized incidence ratio is 1.0 and characteristics of two groups with doses ≥150 mGy are similar, speaks of the lack of a significant radiation effect. The obtained results of the analysis confirm our view of the necessity to continue the study.

Vasectomy and the risk of prostate cancer in a Finnish nationwide population-based cohort

Introduction & objectivesThere are conflicting reports on the association of vasectomy and the risk of prostate cancer (PCa). Our objective was to evaluate the association between vasectomy and PCa from a nationwide cohort in Finland. Materials & methodsSterilization registry of Finland and the Finnish Cancer Registry data were utilized to identify all men who underwent vasectomy between years 1987–2014 in Finland. Standard incidence ratio (SIR) for PCa as well as all-cause standardized mortality ratios (SMR) were calculated. ResultsWe identified 38,124 men with vasectomy with a total of 429,937 person-years follow-up data. The median age at vasectomy was 39.7 years (interquartile range [IQR] 35.9–44.0), after vasectomy PCa was diagnosed in 413 men (122 cases 0–10 years, 219 cases 10–20 years and 72 cases >20 years from vasectomy). SIR for PCa for the vasectomy cohort was 1.15 (95% CI: 1.04–1.27). By the end of follow-up, 19 men had died from PCa, while the expected number was 20.5 (SMR 0.93 [95%CI: 0.56–1.44]). The overall mortality was decreased (SMR 0.54 [95%CI: 0.51-0.58]) among men with vasectomy. ConclusionWe found a small statistically significant increase in PCa incidence after vasectomy, but in contrast the mortality of vasectomized men was significantly reduced. This may be due to higher likelihood of vasectomized men to undergo prostate-specific antigen testing, having healthier general lifestyle and other biological factors e.g. high reproductive fitness.

Classification and diagnostic prediction of prostate cancer using gene expression and artificial neural networks

Prostate cancer is the fourth most common cancer among all cancers and the second most common cancer in men. The rate of increase in prostate cancer incidence is higher than the overall increase of cancer incidents. 68% of prostate cancer cases are from developed countries. There has been very little research on the most suitable techniques for analysing prostate cancer gene expression datasets to identify those genes that may be most related to prostate cancer. This paper attempts to identify significant (influential) attributes in a well-established prostate cancer gene expression dataset consisting of over 12,533 attributes for 102 samples (50 normal, 52 tumour). Several (7) different statistical and artificial intelligence (AI)-based feature selection methods were paired with four different classifiers, namely ANNs, Naive Bayes, AdaBoost and J48. Prediction experiments are carried using ANNs with unseen sample testing. In our experiments, ANNs outperformed all other approaches for classification with sequential forward feature selection (SFFS), achieving 100% accuracy. Naive Bayes and AdaBoost achieved best accuracy of 96.3 and 93.13% with support vector machine (SVM) attribute selection, whereas J48 could get only 89.21% with SFFS approach. For prediction experiments, ANNs obtained an accuracy of 95.1% with SVM attribute selection (correctly predicting 96 out of 102 samples). Finally, by investigating National Center for Biotechnology Information database it is found that 21 out of 24 attributes (87.5%) that belong to SVM attribute selection have a reference to cancer/tumour, thereby establishing a link between feature selection and biological plausibility. The main contribution of this paper is in identifying the importance of pairing the most appropriate feature selection strategy with the most appropriate classification strategy when dealing with significantly underdetermined data. This paper also emphasizes differences and similarities between the influence of classification and prediction of prostate cancer. There is another new approach we considered while doing the classification and prediction experiments. Apart from using 7 different feature selection approaches, we have derived new set of attributes by adding all attributes (union), selecting common attributes (intersection) and rest of the attributes (not common).

Current and Future Burden of Prostate Cancer in Songkhla, Thailand: Analysis of Incidence and Mortality Trends From 1990 to 2030.

PurposeProstate cancer is the second most common malignancy among men worldwide, and it poses a significant public health burden that has traditionally been limited mostly to developed countries. However, the burden of the disease is expected to increase, affecting developing countries, including Thailand. We undertook an analysis to investigate current and future trends of prostate cancer in the province of Songkhla, Thailand, using data from the Songkhla Cancer Registry from 1990 to 2013.MethodsJoinpoint regression analysis was used to examine trends in age-adjusted incidence and mortality rates of prostate cancer and provide estimated annual percent change (EAPC) with 95% CIs. Age-period-cohort (APC) models were used to assess the effect of age, calendar year, and birth cohort on incidence and mortality rates. Three different methods (Joinpoint, Nordpred, and APC) were used to project trends from 2013 to 2030.ResultsEight hundred fifty-five cases of prostate cancer were diagnosed from 1990 to 2013 in Songkhla, Thailand. The incidence rates of prostate cancer significantly increased since 1990 at an EAPC of 4.8% (95% CI, 3.6% to 5.9%). Similarly, mortality rates increased at an EAPC of 5.3% (95% CI, 3.4% to 7.2%). The APC models suggest that birth cohort is the most important factor driving the increased incidence and mortality rates of prostate cancer. Future incidence and mortality of prostate cancer are projected to continue to increase, doubling the rates observed in 2013 by 2030.ConclusionIt is critical to allocate resources to provide care for the men who will be affected by this increase in prostate cancer incidence in Songkhla, Thailand, and to design context-appropriate interventions to prevent its increasing burden.

ANALYSIS OF THE INCIDENCE OF PROSTATE CANCER IN THE ROSTOV REGION FOR THE YEARS 2001–2016: SPATIOTEMPORAL STATISTICS

Introduction . Oncological diseases is a serious medico-social problem of modern society. The article presents the analysis of prostate cancer morbidity with consideration of regional health level differences. Objective . To conduct spatial-temporal analysis of prostate cancer incidence in Rostov region; to identify areas with a statistically significant increase in the incidence of prostate cancer; to identify regional differences (environmental determinism) in the development of cancer in the southern Federal district. Materials and methods . We’ve analysed incidence of prostate cancer in the Rostov region for the period of 2001-2016. The analysis has been performed using tools spatio-temporal statistics on software ArcGis 10 *. Results . Areas and cities of Rostov region with a statistically significant increase in prostate cancer incidence were identified. It has been shown that in the regions and cities of the Rostov region with a low level of medical-ecological safety had a statistically significant increase in prostate cancer incidence Conclusions . The results can serve as a basis for the directional analysis of factors causing increased risk of cancer and development on this basis strategies for monitoring and prevention of cancer diseases in the Rostov region.

Abstract 5210: Incidence and mortality trends of prostate cancer in southern Thailand

Abstract Background: Prostate cancer is one of the most commonly diagnosed cancers in men worldwide. In Asia, the incidence of prostate cancer is expected to increase in the next decades as the population ages and as developing Asian countries undergo the epidemiologic transition. There is a scarcity of studies on the epidemiology of prostate cancer in Thailand. The characterization and projection of the burden of prostate cancer are important to design cost-effective strategies for the prevention and control of this disease. The purpose of this study is to examine incidence and mortality trends of prostate cancer in southern Thailand. Methods: Incident prostate cancer cases from the Songkhla cancer registry were used to analyze incidence and mortality trends; complete data on incidence was available from 1990-2013 and data on mortality was available from 1990-2010. Characteristics of the cases on sociodemographic factors and tumor characteristics were collected, as was vital status. Joinpoint analysis was used to examine the incidence and mortality trends and calculate the annual percent change (APC). The number of joinpoints, slope of the trends, and their significance was determined by permutation tests. Incidence and mortality rates were standardized to the Segi's world standard population. Results: Eight hundred fifty-five prostate cancer cases were diagnosed from 1990 to 2013. The median age at diagnosis was 74 and 89.6% of the diagnosed cases were Buddhist, with the remainder being Muslim. The majority (79.8%) of prostate cancers were unstaged. However, among those cases whose tumors were staged, the distribution was as follows: 3.5% stage I, 17.9% stage II, 2.9% stage III, 75.7% stage IV. The proportion of unstaged tumors decreased during the period 2005-2009 compared to earlier periods, and there was an increase in the proportion of stage II tumors for the same period. The overall prostate cancer incidence rates increased significantly at an APC of 5.1% (95%CI: 3.8, 6.4) from 1990 to 2013. Among Buddhist men, the APC was very similar to the overall incidence (APC: 5.2%, 95%CI: 4.0, 6.5), while we observed a very low incidence rate and no evidence of an increasing trend in Muslim men. As of 2010, 72.7% of the cases had died. Similar to incidence rates, prostate cancer mortality rates have significantly increased at and APC of 3.2% (95CI%: 1.7, 4.8) from 1990 to 2010. Conclusion: This analysis showed that there has been a significant increase in prostate cancer incidence and mortality in Southern Thailand during the period 1990-2013. Next steps include assessing the effects of age, calendar year, and birth-cohort on the incidence and mortality of prostate cancer and projection of the incidence and mortality rates over the next fifteen years in order to fully characterize this cancer and help to design strategies to reduce the future burden of prostate cancer in Thailand. Citation Format: Christian Alvarez, Shama Virani, Rafael Meza, Laura Rozek, Hutcha Sriplung, Alison M. Mondul. Incidence and mortality trends of prostate cancer in southern Thailand. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5210.

Glutathione Peroxidase 3 Inhibits Prostate Tumorigenesis in TRAMP Mice.

Glutathione peroxidase 3 (GPx3) is involved in protecting cells from oxidative damage, and down-regulated levels of expression have been found in prostate cancer samples. We hypothesize that loss of the GPx3 increases the rate of prostate carcinogenesis and generated GPx3-deficient transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Prostate cancer incidence and progression were determined in TRAMP, TRAMP/GPx3 (+/-) HET, and TRAMP/GPx3 (-/-) KO mice at 8, 16, and 20 weeks of age. We found that GPx3 expression was decreased in TRAMP mice and not detected in GPx3 KO mice both in mRNA and protein levels. Disruption of GPx3 expression in TRAMP mice increased the GU tract weights and the histopathological scores in each lobes with increased proliferation rates. Moreover, inactivation of one (+/-) or both (-/-) alleles of GPx3 resulted in increase in prostate cancer incidence with activated Wnt/β-catenin pathway. Our results provide the first in vivo molecular genetic evidence that GPx3 does indeed function as a tumor suppressor during prostate carcinogenesis. Prostate 76:1387-1398, 2016. © 2016 Wiley Periodicals, Inc.

Prostate Cancer in Pilots.

Aviation exposes pilots to various occupationally related hazards, including ionizing radiation and chemical combustion. The possibility of increased prostate cancer incidence and mortality among pilots is a subject of debate. This systematic review and meta-analysis aims to summarize the supporting evidence and determine the magnitude of association. All studies reporting prostate cancer incidence and mortality in pilots compared to the general population were included regardless of language or size. The comprehensive search included multiple databases and manual search. A random effect model was used to pool relative risks (RR) across studies. The final search yielded nine studies with good methodological quality. Four studies reported the incidence of prostate cancer while six reported on mortality. Pilots had a small but statistically significant increase in the risk of developing prostate cancer [RR 1.20; 95% confidence interval (CI), 1.08-1.33], but not in prostate cancer mortality (RR 1.20; 95% CI, 0.91-1.60). Pilots appear to have a very small increase in prostate cancer incidence, but not in mortality. The clinical significance of this finding is uncertain.

PSA Screening for Prostate Cancer: Why Saying No is a High-Value Health Care Choice.

Enthusiasm for cancer screening and treatment of screen-detected cancer has led to widespread prostate-specific antigen (PSA) screening, a marked increase in prostate cancer incidence, and high use of surgical, radiation, and androgen deprivation treatment for screen-detected disease. This has occurred in advance of a full understanding of the clinical and financial tradeoffs. Although questions remain whether lifetime benefits outweigh harms and costs, data indicate that this balance is not favorable through at least 15 years. This article outlines a conceptual framework for determining the value of screening strategies according to screening and treatment intensity. We describe 4 main cancer screening goals and examine whether PSA screening and treatment achieve these goals and thus provide high-value care. Available evidence demonstrates that PSA screening provides at best a small reduction in prostate cancer mortality, and no reduction in all-cause mortality. High-intensity PSA screening and treatment currently practiced in the United States result in substantial harms and large health care expenditures-it is low-value care. The health importance of prostate cancer and the financial costs to patients and society require improved detection and treatment strategies that produce greater value to patients. We propose lower-intensity, higher-value options. However, until evidence supports a higher-value alternative to current PSA screening strategies, physicians should recommend against PSA screening, policymakers should encourage reduced screening, and most men should say no to the PSA test.

Concomitant Gleason Score ≥ 7 prostate cancer is an independent prognosticator for poor survival in nonmetastatic bladder cancer patients undergoing radical cystoprostatectomy.

In bladder cancer (BCa) patients undergoing radical cystoprostatectomy (RCPx), concomitant prostate cancer (PCa) is a common finding. Up to now there is no clear evidence to suggest that concomitant PCa is a predictor of outcome in these patients. Aim of this study was to assess incidence and clinicopathologic characteristics of concomitant PCa in RCPx specimen and correlate it to survival parameters from a single-centre material over two decades. All men who had undergone RCPx for BCa at our institution between 1994 and 2013 were included in this study. Clinicopathologic parameters for BCa and PCa were evaluated and correlated with outcome parameters. Survival analysis was performed for the subgroup of nonmetastatic organ-confined BCa to evaluate the role of concomitant Gleason Score (GS) ≥7 PCa. Of 945 men who had undergone RCPx for BCa, concomitant PCa was present in 237 patients (25.1 %). There was a significant increase in PCa incidence from 18.9 to 32.3 % between 1994 and 2013 (p = 0.009). Concomitant PCa represented a more aggressive phenotype at the end of the study (p = 0.037). In nonmetastatic organ-confined BCa, concomitant GS ≥7 PCa (HR 3.09; p = 0.0001) and age > 68 (HR 1.80; p = 0.0004) were independent negative predictors for overall survival. Concomitant PCa in RCPx specimen of BCa patients is a common finding. The incidence of concomitant PCa has significantly increased within 2 decades, presenting a more aggressive phenotype. Age and in particular concomitant GS ≥7 PCa are independent prognosticators for poor survival in patients with nonmetastatic organ-confined BCa.

Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk.

Testosterone plays a central role in male development and health. Likewise, androgen deficiency, or hypogonadism, is associated with a variety of symptoms including decreased energy, diminished libido and erectile dysfunction, among others. Male androgen levels steadily decline with age, and, in a subset of symptomatic older men, can result in late-onset hypogonadism (LOH). Over the last decade, increased awareness of hypogonadism among patients and providers has led to a significant rise in the use of testosterone replacement therapy (TRT) for hypogonadism, and especially in LOH. Accompanying the rise in TRT are concerns of potential adverse effects, including cardiovascular risks and the promotion of prostate cancer. The 'androgen hypothesis' asserts that prostate cancer development and progression is driven by androgens, and thus TRT has the theoretical potential to drive prostate cancer development and progression. In this review, we examine existing data surrounding testosterone and prostate cancer. There is significant evidence that androgens promote prostate cancer in experimental systems. However, there is no clear evidence that elevations in endogenous testosterone levels promote the development of prostate cancer in humans. As a result of experimental and historical data on the progression of prostate cancer following TRT, there has been widespread belief that TRT will promote disease progression in prostate cancer patients. Despite these fears, there are a growing number of studies demonstrating no increase in prostate cancer incidence among men on TRT. Furthermore, in studies involving a small number of patients, there has been no discernable increase in disease progression in prostate cancer patients on TRT. While data from large, prospective, randomized, controlled trials are absent, TRT in select prostate cancer patients is likely safe. In the end, the use of TRT in prostate cancer patients is still considered experimental and should only be offered after well-informed shared decision making and with close monitoring.

Metastatic Prostate Cancer Incidence and Prostate-specific Antigen Testing: New Insights from the European Randomized Study of Screening for Prostate Cancer

BackgroundThe European Randomized Study of Screening for Prostate Cancer (ERSPC) has shown a 21% reduction in prostate cancer (PCa) mortality and a 1.6-fold increase in PCa incidence with prostate-specific antigen (PSA)-based screening (at 13 yr of follow-up). We evaluated PCa incidence by risk category at diagnosis across the study arms to assess the potential impact on PCa mortality. Design, setting, and participantsInformation on arm, centre, T and M stage, Gleason score, serum PSA at diagnosis, age at randomisation, follow-up time, and vital status were extracted from the ERSPC database. Four risk categories at diagnosis were defined: 1, low; 2, intermediate; 3, high; 4, metastatic disease. PSA (≤100 or >100 ng/ml) was used as the indicator of metastasis. Outcome measurements and statistical analysisIncidence rate ratios (IRRs) for screening versus control arm by risk category at diagnosis and follow-up time were calculated using Poisson regression analysis for seven centres. Follow-up was truncated at 13 yr. Missing data were imputed using chained equations. The analyses were carried out on an intention-to-treat basis. Results and limitationsIn the screening arm, 7408 PCa cases were diagnosed and 6107 in the control arm. The proportion of missing stage, Gleason score, or PSA value was comparable in the two arms (8% vs 10%), but differed among centres. The IRRs were elevated in the screening arm for the low-risk (IRR: 2.14; 95% CI, 2.03–2.25) and intermediate-risk (IRR: 1.24; 95% CI, 1.16–1.34) categories at diagnosis, equal to unity for the high-risk category at diagnosis (IRR: 1.00; 95% CI, 0.89–1.13), and reduced for metastatic disease at diagnosis (IRR: 0.60; 95% CI, 0.52–0.70). The IRR of metastatic disease had temporal pattern similar to mortality, shifted forwards an average of almost 3 yr, although the mortality reduction was smaller. ConclusionsThe results confirm a reduction in metastatic disease at diagnosis in the screening arm, preceding mortality reduction by almost 3 yr. Patient summaryThe findings of this study indicate that the decrease in metastatic disease at diagnosis is the major determinant of the prostate cancer mortality reduction in the European Randomized study of Screening for Prostate Cancer.

A critical review of the epidemiology of Agent Orange/TCDD and prostate cancer.

To inform risk assessment and regulatory decision-making, the relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and prostate cancer requires clarification. This article systematically and critically reviews the epidemiologic evidence on the association between exposure to TCDD or Agent Orange, a TCDD-contaminated herbicide used during the Vietnam War, and prostate cancer risk. Articles evaluated include 11 studies of three cohorts, four case–control or cross-sectional studies, and three case-only studies of military veterans with information on estimated Agent Orange or TCDD exposure; 13 studies of seven cohorts, one case–control study, and eight proportionate morbidity or mortality studies of Vietnam veterans without information on Agent Orange exposure; 11 cohort studies of workers with occupational exposure to TCDD; and two studies of one community cohort with environmental exposure to TCDD. The most informative studies, including those of Vietnam veterans involved in Agent Orange spraying or other handling, herbicide manufacturing or spraying workers with occupational TCDD exposure, and community members exposed to TCDD through an industrial accident, consistently reported no significant increase in prostate cancer incidence or mortality. Only some potentially confounded studies of Vietnam veterans compared with the general population, studies with unreliable estimates of Agent Orange exposure, and analyses of selected subgroups of Vietnam veterans reported positive associations. Overall, epidemiologic research offers no consistent or convincing evidence of a causal relationship between exposure to Agent Orange or TCDD and prostate cancer. More accurate exposure assessment is needed in large epidemiologic studies to rule out a causal association more conclusively.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-014-9931-2) contains supplementary material, which is available to authorized users.

Prostate Cancer Mortality in Areas With High and Low Prostate Cancer Incidence

BackgroundThe effect of prostate-specific antigen (PSA) screening on prostate cancer mortality remains debated, despite evidence from randomized trials. We investigated the association between prostate cancer incidence, reflecting uptake of PSA testing, and prostate cancer mortality.MethodsThe study population consisted of all men aged 50 to 74 years residing in eight counties in Sweden with an early increase in prostate cancer incidence and six counties with a late increase during two time periods. Incidence of metastatic prostate cancer was investigated in the period from 2000 to 2009, and prostate cancer–specific mortality and excess mortality were investigated in the period from 1990 to 1999 and the period from 2000 to 2009 by calculating rate ratios for high- vs low-incidence counties and rate ratios for the period from 2000 to 2009 vs the period from 1990 to 1999 within these two groups. All statistical tests were two-sided.ResultsThere were 4528134 person-years at risk, 1577 deaths from prostate cancer, and 1210 excess deaths in men with prostate cancer in high-incidence counties and 2471373 person-years at risk, 985 prostate cancer deaths, and 878 excess deaths in low-incidence counties in the period from 2000 to 2009. Rate ratios in counties with high vs low incidence adjusted for time period were 0.81 (95% confidence interval [CI] = 0.73 to 0.90) for prostate cancer– specific mortality and 0.74 (95% CI = 0.64 to 0.86) for excess mortality, and the rate ratio of metastatic prostate cancer was 0.85 (95% CI = 0.79 to 0.92).ConclusionsThe lower prostate cancer mortality in high-incidence counties reflecting a high PSA uptake suggests that more-intense as compared with less-intense opportunistic PSA screening reduces prostate cancer mortality.

Epidemiology of prostate cancer in the Asia-Pacific region.

The purpose of this paper was to examine and compare available data on incidence, mortality and survival for countries in the Asia-Pacific region. Incidence data were obtained from GLOBOCAN 2008, other online data sources and individual cancer registries. Country-specific mortality statistics by individual year were sourced from the World Health Organization Statistical Information System Mortality Database. All incidence and mortality rates were directly age-standardised to the Segi World Standard population and joinpoint models were used to assess trends. Data on survival were obtained from country-specific published reports where available. Approximately 14% (122,000) of all prostate cancers diagnosed worldwide in 2008 were within the Asia-Pacific region (10 per 100,000 population), with three out of every four of these prostate cancer cases diagnosed in either Japan (32%), China (28%) or Australia (15%). There were also about 42,000 deaths due to prostate cancer in the Asia-Pacific region (3 per 100,000). For the nine countries with incidence trend data available, eight showed recent significant increases in prostate cancer incidence. In contrast, recent decreases in prostate cancer mortality have been reported for Australia, Japan and New Zealand, but mortality has increased in several other countries. The lack of population-based data across most of the countries in this region limits the ability of researchers to understand and report on the patterns and distribution of this important cancer. Governments and health planners typically require quantitative evidence as a motivation for change. Unless there is a widespread commitment to improve the collection and reporting of data on prostate cancer it is likely that the burden of prostate cancer will continue to increase. Enhancing knowledge transfer between countries where there are differentials in capacity, policy and experience may provide the necessary impetus and opportunity to overcome at least some of the existing barriers.

Molecular Pathways Involved in Prostate Carcinogenesis: Insights from Public Microarray Datasets

BackgroundProstate cancer is currently the most frequently diagnosed malignancy in men and the second leading cause of cancer-related deaths in industrialized countries. Worldwide, an increase in prostate cancer incidence is expected due to an increased life-expectancy, aging of the population and improved diagnosis. Although the specific underlying mechanisms of prostate carcinogenesis remain unknown, prostate cancer is thought to result from a combination of genetic and environmental factors altering key cellular processes. To elucidate these complex interactions and to contribute to the understanding of prostate cancer progression and metastasis, analysis of large scale gene expression studies using bioinformatics approaches is used to decipher regulation of core processes.Methodology/Principal FindingsIn this study, a standardized quality control procedure and statistical analysis (http://www.arrayanalysis.org/) were applied to multiple prostate cancer datasets retrieved from the ArrayExpress data repository and pathway analysis using PathVisio (http://www.pathvisio.org/) was performed. The results led to the identification of three core biological processes that are strongly affected during prostate carcinogenesis: cholesterol biosynthesis, the process of epithelial-to-mesenchymal transition and an increased metabolic activity.ConclusionsThis study illustrates how a standardized bioinformatics evaluation of existing microarray data and subsequent pathway analysis can quickly and cost-effectively provide essential information about important molecular pathways and cellular processes involved in prostate cancer development and disease progression. The presented results may assist in biomarker profiling and the development of novel treatment approaches.

Prostate cancer in Denmark 1978–2009 — trends in incidence and mortality

Background. The incidence of prostate cancer (PC) has increased during the last 15 years in Denmark, whereas the mortality has remained largely unchanged. This register study aimed to investigate the trends in PC incidence and mortality in Denmark 1978–2009 with special focus on the recent 15 years. Material and methods. From the nationwide Danish Cancer Registry and Register of Causes of Death, we obtained information on all cases of PC and all deaths in Denmark during 1978–2009. Age-standardised (World Standard Population) incidence and mortality rates were computed for five-year calendar periods (1978–2007) and a two-year calendar period (2008–2009). Trends in incidence rates were estimated for specific age groups, birth cohorts, and clinical stage. Results. The age-standardised incidence rate of PC increased from 29.2 per 100 000 person-years in 1978–1982 to 76.2 per 100 000 person-years in 2008–2009. The incidence increase began primarily in the mid-1990s. The corresponding mortality rates of PC remained largely unchanged during the entire study period; around 19 per 100 000 person-years. The incidence increase was most pronounced among men aged 60 + years. A clear pattern was also seen for selected birth cohorts, with increasing incidence rates among the youngest cohorts, and the highest relative increase in age-specific incidence rates was seen among men born between 1943 and 1947. The distribution of stage changed from 1998, with an increasing proportion of PC patients with localised disease. Conclusion. The observed increase in PC incidence during the period 1993–2009 in Denmark may be attributed primarily to increasing unsystematic use of prostate specific antigen (PSA) testing. The mortality rates remained stable during the same period suggesting that there is not yet any major influence of intensified PSA screening and more frequent use of curatively intended therapy on the overall prognosis of PC.