Incidence Of Metastatic Prostate Cancer Research Articles

The Association of County-level Prostate-specific Antigen Screening with Metastatic Prostate Cancer and Prostate Cancer Mortality

Background and objectiveThere exists ongoing debate about the benefits and harms of prostate-specific antigen (PSA) screening for prostate cancer. This study sought to evaluate the association of county-level PSA screening rates with county-level incidence of metastatic prostate cancer and prostate cancer mortality in the USA. MethodsThis ecological study used data from the 2004–2012 Behavioral Risk Factor Surveillance System (BRFSS) to build a multilevel mixed-effect model with poststratification using US Census data to estimate county-level PSA screening rates for all 3143 US counties adjusted for age, race, ethnicity, and county-level poverty rates. The exposure of interest was average county-level PSA screening rate from 2004 to 2012, defined as the proportion of men aged 40–79 yr who underwent PSA screening within the prior 2 yr. The primary outcomes were county-level age-adjusted incidence of regional/distant prostate cancer during 2015–2019 and age-adjusted prostate cancer mortality during 2016–2020. Key findings and limitationsA total of 416221 male BRFSS respondents aged 40–79 yr met the inclusion criteria and were used in the multilevel mixed-effect model. The model was poststratified using 63.4 million men aged 40–79 yr from all 3143 counties in the 2010 Decennial Census. County-level estimated PSA screening rates exhibited geographic variability and were pooled at the state level for internal validation with direct BRFSS state-level estimates, showing a strong correlation with Pearson correlation coefficients 0.77–0.90. A 10% higher county-level probability of PSA screening in 2004–2012 was associated with a 14% lower county-level incidence of regional/distant prostate cancer in 2015–2019 (rate ratio 0.86, 95% confidence interval [CI] 0.85–0.87, p < 0.001) and 10% lower county-level prostate cancer mortality in 2016–2020 (rate ratio 0.90, 95% CI 0.89–0.91, p < 0.001). Conclusions and clinical implicationsIn this population-based ecological study of all US counties, higher PSA screening rates were associated with a lower incidence of regional/distant prostate cancer and lower prostate cancer mortality at extended follow-up. Patient summaryUS counties with higher rates of prostate-specific antigen (PSA) screening had significantly lower rates of metastatic prostate cancer and prostate cancer mortality in subsequent years. These data may inform shared decision-making regarding PSA screening for prostate cancer.

Untreated hypogonadism and testosterone replacement therapy in hypogonadal men are associated with a decreased risk of subsequent prostate cancer: a population-based study.

We sought to understand the relationship between hypogonadism and testosterone replacement therapy (TRT) in hypogonadal men on the risk of developing localized and metastatic prostate cancer. We used the Merative MarketScan database of commercial claims encounters to identify men diagnosed with hypogonadism. These men were matched to eugonadal men who served as controls. Multivariate negative binomial regression analysis of prostate cancer diagnoses, hypogonadism, and TRT in hypogonadal men adjusting for various known confounding factors was used to understand the impact of hypogonadism and TRT on prostate cancer risk. We identified 3,222,904 men who met inclusion criteria, of which 50% were diagnosed with hypogonadism (1,611,452) and each were matched to a control (1,611,452). The incidence of prostate cancer was 2.16%, 1.55%, and 1.99% in eugonadal controls, hypogonadal men on TRT, and hypogonadal men without TRT, respectively (p < 0.001). Untreated hypogonadism was independently associated with a decreased risk of localized prostate cancer (IRR 0.46, 95% CI 0.43-0.50, p < 0.001) compared to eugonadal controls. Hypogonadal men on TRT also had a significantly decreased risk of localized prostate cancer (IRR 0.49, 95% CI 0.45-0.53, p < 0.001). Furthermore, hypogonadal men on TRT (IRR 0.21, 95% CI 0.19-0.24, p < 0.001) or without TRT (IRR 0.20, 95% CI 0.18-0.22, p < 0.001) both had significantly decreased risk of metastatic prostate cancer, respectively. Our population-based analysis suggests that untreated hypogonadism in men is associated with a 50% decreased incidence of localized prostate cancer and an 80% decreased incidence of metastatic prostate cancer. TRT in hypogonadal men was also associated with a decreased risk of subsequent prostate cancer. Further research is needed to better understand the relationship between hypogonadism and TRT in hypogonadal men on the riskof subsequent prostate cancer.

Racial and income characteristics and the burden of illness among metastatic prostate cancer patients.

e17064 Background: The incidence of metastatic prostate cancer has increased dramatically between 2010 and 2017 in the United States. Since the racial and ethnic mix of the population of the United States (U.S.) have changed between the years 2010 and 2020–it is extremely important to understand its effects on prostate cancer outcomes. Therefore, we investigated the burden of illness across racial groups and income levels among patients diagnosed with metastatic prostate cancer. Methods: This study utilized the U.S. 2017 National Inpatient Sample database to identify hospitalizations with a primary diagnosis of prostate cancers. We evaluated associations between race and income levels, and the burden of illness (total charges and length of stay (LOS)) adjusting for patient and clinical factors with multivariable generalized linear models. Results: A total of 63,880 metastatic prostate cancer patients were included in the study, and the median [IQR] age was 74 [66, 82]. There were 65.6% Whites, 20.6% Blacks, 7.7% Hispanics, and 6.1% Asians and Others. Blacks had a higher prevalence in the age group 45-55 (34.2%), when compared to 55-64 (29.8%), or &gt; 65 (17.6%) age group. There were only 10% Blacks and 4.9% Hispanics living in high-income neighborhoods, whereas this was 75.5% for Whites. In the adjusted analysis, compared to the Whites, Hispanics (1.43; 95%CI-1.29- 1.57), and Asians and Others (1.39; 95%CI- 1.25- 1.56) had a higher total charge; and compared to Whites, Blacks had a higher LOS (1.28; 95%CI-1.15-1.44). Compared to high-income neighborhoods, those living in the 26th to 50th percentile had a lower total charge (0.86; 95%CI- 0.78-0.94). Compared to the &gt; 65 years age group, the 44-55 age group had a lower total charge (0.73; 95%CI-0.61-0.89). Compared to patients with Medicare, those with Private Insurance (0.87; 95%CI- 0.80-0.94) and Self-pay and Others (0.73; 95C%CI-0.62–0.86) had a lower total charge. And when compared to non-elective admissions, elective admissions had a higher total charge (1.44; 95%CI-1.29- 1.59). Conclusions: Hispanics and Asians and Others had a higher burden of illness, and Blacks had a higher LOS. Patients who reside in lower income neighborhoods had lower total charges. Understanding prostate cancer outcomes by race and income is crucial to designing strategies to improve access to care.

Re: Association of Prostate-specific Antigen Screening Rates with Subsequent Metastatic Prostate Cancer Incidence at US Veterans Health Administration Facilities: Prostate cancer screening needs not only to be well meant but also well done

Re: Association of Prostate-specific Antigen Screening Rates with Subsequent Metastatic Prostate Cancer Incidence at US Veterans Health Administration Facilities: Prostate cancer screening needs not only to be well meant but also well done

Choice of imputation method for missing metastatic status affected estimates of metastatic prostate cancer incidence

ObjectivesTo study how handling missing data on M stage in a clinical cancer register affects estimates of incidence of metastatic prostate cancer. Study Design and SettingEstimates of age-standardized incidence of metastatic prostate cancer were obtained by the use of data in a population-based clinical cancer register in Sweden and using four methods for imputation of missing M stage. Adjusted survival was used to compare men with known and imputed M stage. ResultsThe proportion of men with missing M stage was high (66%) and varied according to the risk group and over calendar time. The estimated incidence of metastatic disease varied depending on imputation method, with all methods indicating a decreasing incidence over time. A combination of deterministic imputation (DI) and multiple imputation (MI) produced adjusted survival curves for men with imputed M stage that best resembled the survival for men with known M stage. ConclusionsPlausible estimates of incidence of metastatic prostate cancer in clinical cancer registers can be obtained by the use of a combination of DI of missing M stage and MI.

Association of Prostate-Specific Antigen Screening Rates and Subsequent Metastatic Prostate Cancer Incidence in a National Healthcare System

<h3>Purpose/Objective(s)</h3> There is substantial controversy about the benefit of prostate-specific antigen (PSA) screening. PSA screening rates have declined since 2008 due to changing practice guidelines and conflicting clinical trial results regarding the benefit of screening. Since then, the incidence of metastatic prostate cancer (mPCa) has risen; however, there is no direct epidemiologic evidence of a correlation between population PSA screening rates and subsequent mPCa rates. <h3>Materials/Methods</h3> We used data from the United States Veterans Healthcare Administration (VHA) to calculate yearly PSA screening rates, long-term non-screening rates (no PSA measured in prior three years), and age-adjusted mPCa incidence rates from 2005 to 2019. Rates are reported per 100,000 men and were aggregated by race, age group, and VHA facility (128 facilities). We used random effects linear regression to examine the influence of yearly facility-level PSA screening rates from 2010-2013 on subsequent facility-level mPCa incidence from 2014-2019, adjusting for population demographics. <h3>Results</h3> The cohort included 4.7 million men in 2005 and increased to 5.4 million in 2019. PSA screening rates declined from a high of 50.8% in 2008 to 37% in 2019, with declines in all age and race groups; the long-term non-screening rate similarly increased in this period. mPCa incidence increased from a low of 4.6 in 2008 to 7.9 in 2019, driven by increases in the 55-69 and 70+ year old age groups. Lower facility-level PSA screening rates were associated with higher subsequent mPCa incidence (0.87 unit increase in 2014-2019 mPCa incidence rate per 10% decrease in 2010-2013 PSA screening rate, 95% confidence interval [CI] 0.58 to 1.15, p<0.001). Similarly, higher long-term non-screening rates were associated with higher subsequent mPCa incidence (1.61 unit increase in 2014-2019 mPCa incidence rate per 10% increase in 2010-2013 long-term non-screening rate, 95% CI 1.14 to 2.08, p<0.001). <h3>Conclusion</h3> From 2008 to 2019, PSA screening rates declined and long-term non-screening rates increased in the national VHA system. Lower facility-level PSA screening rates were associated with higher subsequent rates of mPCa. These data can be used to inform shared decision making about the potential benefits of PSA screening in men who wish to reduce their risk of prostate cancer metastases.

Screening for prostate cancer: protocol for updating multiple systematic reviews to inform a Canadian Task Force on Preventive Health Care guideline update

PurposeTo inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for prostate cancer in adults aged 18 years and older in primary care. This protocol outlines the planned scope and methods for a series of systematic reviews.MethodsUpdates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with a prostate-specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false-positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. The quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding the choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomized, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, gray literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome.DiscussionThe series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older.Systematic review registrationThis review has been registered with PROSPERO (CRD42022314407) and is available on the Open Science Framework (osf.io/dm32k).

Association of Prostate-Specific Antigen Screening Rates With Subsequent Metastatic Prostate Cancer Incidence at US Veterans Health Administration Facilities

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.

Re: Trends in Incidence of Metastatic Prostate Cancer in the US

Re: Trends in Incidence of Metastatic Prostate Cancer in the US

Ocular complications with the use of radium-223: a case series

BackgroundRadium-223 is used for the treatment of osseous metastases in castrate-resistant prostate cancer, and has been shown to increase time to the first skeletal-related event, reduce the rate of hospitalization, and improve quality of life. It is well tolerated, with hematologic toxicity as the main adverse event. Thus far, no ocular complication has been reported in the literature after initial administration of radium-223 with a single case reported of ocular complications after a patient’s second course of radium-223.Case presentationsWe present three cases of ocular complications after the use of radium-223 in patients with metastatic prostatic adenocarcinoma. Ocular complications presented as blurry vision, and formal diagnosis included uveitis and hyphema.ConclusionsDocumentation of adverse events is exceedingly important due to the high incidence of metastatic prostate cancer and increasing interest for the use of radium-223 in other osteoblastic disease. The authors postulate that these ocular complications may be a result of radiation’s potential effect on neovascularization, polypharmacy, or the biomolecular effects of radium-223 on integral signaling proteins, potentially coupled with poor underlying ocular health.

Trends in Incidence of Metastatic Prostate Cancer in the US

The US Preventive Services Task Force (USPSTF) has recommended against routine prostate-specific antigen (PSA)-based prostate cancer (PCa) screening, initially for men older than 75 years in 2008, and then for all men in 2012. Concern has been raised that, by recommending against screening, and thus early detection, the USPSTF recommendations may be associated with an increase in the incidence of metastatic PCa (mPCa). To explore the incidence of mPCa before and after the USPSTF recommendations against routine PCa screening. This population-based cohort study used the recently released Surveillance, Epidemiology, and End Results (SEER) 18 registry incidence data to identify men aged 45 years and older with a diagnosis of invasive PCa from 2004 through 2018. Data were analyzed from January 1, 2004 to December 31, 2018. Outcomes were assessed before vs after the USPSTF recommendations against routine screening. Annual age-adjusted incidence rates per 100 000 population of mPCa (defined using SEER Summary Stage and American Joint Committee on Cancer [AJCC] staging systems), with adjustments for age structure and reporting delay from 2004 to 2011, according to race and age were examined. Annual percentage changes (APCs) were calculated to quantify changes in the annual incidence rates. From 2004 to 2018, a total of 836 282 patients with PCa were recorded in the SEER database; 26 642 (56.5%) distant mPCa cases were reported in men aged 45 to 74 years, and 20 507 (43.5%) cases were reported in men aged 75 years or older. Among men aged 45 to 74 years, the incidence rate of distant mPCa (SEER Summary staging) remained stable during 2004 to 2010 (APC, -0.4%; 95% CI, -1.7% to 1.1%; P = .60), then increased significantly during 2010 to 2018 (APC, 5.3%; 95% CI, 4.5% to 6.0%; P < .001). In men aged 75 years or older, the incidence rate of distant mPCa decreased from 2004 to 2011 (APC, -1.5%; 95% CI, -3.0% to 0%; P = .046), and then increased from 2011 to 2018 (APC, 6.5%; 95% CI, 5.1% to 7.8%; P < .001). Similar trends were also seen for M1 mPCa defined per the AJCC staging system. These increased trends in mPCa incidence were particularly significant in non-Hispanic White men (2010-2018 APC, 6.9%; 95% CI, 5.4% to 8.4%; P < .001). Analysis of the emerging trends from the most recently released SEER data set (2004-2018) suggests that the incidence rates of mPCa have increased significantly and coincide temporally with the USPSTF recommendations against PCa screening across races and age groups. These mPCa trends are associated with reported changes in screening practices following the USPSTF recommendations.

Systemic Effects Reflected in Specific Biomarker Patterns Are Instrumental for the Paradigm Change in Prostate Cancer Management: A Strategic Paper.

Simple SummaryProstate cancer (PCa) incidence is increasing globally. The costs of treating PCa are currently increasing more rapidly than those of any other cancer, due to an overtreatment of slowly developing disease on one hand and underestimation/therapy resistance of particularly aggressive PCa subtypes on the other hand. How to reverse this trend? PCa is a multi-factorial disease resulting from an imbalanced interplay between health risks and protective factors. Suboptimal behavioural patterns and abnormal stress reactions, amongst others, cause negative systemic effects synergistically involved in PCa development and progression. Further, systemic effects are relevant for the entire human body and, therefore, are reflected in body fluids such as blood. Blood profiles specific for PCa are, therefore, instrumental for the risk assessment in PCa predisposed individuals, targeted disease prevention and personalised treatment algorithms—altogether 3P (predictive, preventive and personalised/PPPM) medicine as a new paradigm in PCa management. This strategic article initiated by the European Association for Predictive, Preventive and Personalised Medicine (EPMA, Brussels) and European Medical Association (EMA, Brussels) and created by an international multi-professional group of experts, highlights systemic effects in PCa initiation, development and progression, demonstrates evident challenges and provides expert recommendations in the framework of 3P medicine.Prostate cancer (PCa) is reported as the most common malignancy and second leading cause of death in America. In Europe, PCa is considered the leading type of tumour in 28 European countries. The costs of treating PCa are currently increasing more rapidly than those of any other cancer. Corresponding economic burden is enormous, due to an overtreatment of slowly developing disease on one hand and underestimation/therapy resistance of particularly aggressive PCa subtypes on the other hand. The incidence of metastatic PCa is rapidly increasing that is particularly characteristic for young adults. PCa is a systemic multi-factorial disease resulting from an imbalanced interplay between risks and protective factors. Sub-optimal behavioural patterns, abnormal stress reactions, imbalanced antioxidant defence, systemic ischemia and inflammation, mitochondriopathies, aberrant metabolic pathways, gene methylation and damage to DNA, amongst others, are synergistically involved in pathomechanisms of PCa development and progression. To this end, PCa-relevant systemic effects are reflected in liquid biopsies such as blood patterns which are instrumental for predictive diagnostics, targeted prevention and personalisation of medical services (PPPM/3P medicine) as a new paradigm in the overall PCa management. This strategic review article highlights systemic effects in prostate cancer development and progression, demonstrates evident challenges in PCa management and provides expert recommendations in the framework of 3P medicine.

Incidence and mortality trends of metastatic prostate cancer: Surveillance, Epidemiology, and End Results database analysis.

In the past decade, prostate cancer screening decreased, raising the concern of delays in diagnosis and leading to an increase in new cases of metastatic prostate cancer. This study evaluated whether these changes may have impacted trends in metastatic prostate cancer incidence and survival. Metastatic prostate cancer diagnoses from 2008-2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) 18 registries. Age-adjusted incidence rates per 100 000 were calculated by time periods and demographic variables. Two-year all-cause and prostate cancer-specific mortality were calculated for patients diagnosed from 2008-2014, and multivariable Cox proportional hazards models were used to evaluate the impact of demographic and clinical variables. Incidence rates of metastatic prostate cancer increased by 18% from 2008-2009 to 2014-2016 (incidence rate ratio [IRR]=1.18, 95% confidence interval [CI] 1.14-1.21). This trend was observed across multiple subgroups but was greatest in non-Hispanic Whites and patients living in counties 0-10% below poverty level. There was an overall decreased risk of all-cause and prostate cancer-specific mortality, but unmarried men and men living in counties >20% below poverty level showed statistically significant increased risk of prostate cancer-specific mortality. Non-Hispanic Whites and the wealthiest subgroups had the largest increase in incidence of metastatic prostate cancer since 2008. Despite trends of decreased risk of prostate cancer-specific mortality, we found certain populations experienced increases in mortality risk. Studies exploring the role of socioeconomic factors on screening and access to newer treatments are needed.

Association of reductions in PSA screening across states with increased metastatic prostate cancer in the United States.

228 Background: While PSA screening was found to reduce prostate cancer metastasis and mortality in a large European randomized trial, PSA screening has also resulted in over-treatment of prostate cancer with significant quality-of-life implications. As a result, the US Preventive Services Task Force (USPSTF) did not recommend PSA screening in 2008 and 2012. It is unknown if reductions in PSA screening were responsible for increased metastatic prostate cancer in the United States. We test this hypothesis by associating longitudinal variations across individual states in PSA screening with their incidence of metastatic prostate cancer at diagnosis from 2002 to 2016. Methods: Age-adjusted incidences of metastatic prostate cancer at diagnosis per 100,000 men were obtained from the North American Association of Central Cancer Registries in 2002 – 2016 for each state. Survey-weighted PSA screening estimates for each state were extracted from the Behavioral Risk Factor Surveillance System, which collects this information for men at least 40 years of age every 2 years from 2002 onward. PSA screening and metastasis data were collated as a multi-panel time series and then analyzed using a random-effects linear regression model with random effects at the state level. Results: There was significant variation between states in the percent of men age &gt;40 years who reported ever receiving PSA screening (range 40.1% to 70.3%) and in the age-adjusted incidence of metastatic prostate cancer at diagnosis (range 3.3 to 14.3 per 100,000). From 2008 to 2016, the mean percentage of men screened decreased (61.8% to 50.5%) whereas the mean incidence of metastatic prostate cancer at diagnosis increased (6.4 to 9.0 per 100,000; Bonferroni adjusted p &lt; 0.001 for both). A random-effects linear regression model demonstrated that longitudinal reductions across states in PSA screening were associated with increased metastatic prostate cancer (regression coefficient per 100,000 men: 14.9, 95% CI 12.3 – 17.5, p &lt; 0.001). This indicated that states with larger declines in PSA screening had larger increases in the incidence of metastatic prostate cancer at diagnosis. Variation in PSA screening explained 27% of the longitudinal variation in metastatic prostate cancer within states. Conclusions: In the context of randomized trial data demonstrating a metastasis reduction with PSA screening, our study strengthens the epidemiologic evidence that reductions in PSA screening may explain some of the recent increase in metastatic prostate cancer at diagnosis in the United States. The trend of rising metastatic disease at diagnosis is a worrisome consequence that needs attention. Thus, we support shared-decision making policies, such as the 2018 USPSTF update, that may optimize PSA screening utilization to reduce the incidence of metastatic prostate cancer in the United States.

Evaluation of the chemopreventive potential of polyprenols from the needles of Picea abies L. and Pinus sylvestris L. using the model of prostate carcinogenesis in male Wistar rats

For decades, one of the most popular ideas in reducing the burden of cancer worldwide is the idea of cancer chemoprevention with low-toxic agents. There is an evidence that polyprenols (polyisoprenoid alcohols) are perspective agents for cancer chemoprevention. The aim of the study is to investigate anticancer activity of the polyprenol complex (the main polyprenols are prenol-14, prenol-15, prenol-16 and prenol-17) against prostate cancer (PCa) and its precursor (prostatic intraepithelial neoplasia, PIN). Material and methods. For induction of prostate carcinogenesis we used modified protocol of two-stage model. Mature male Wistar rats were administrated with single intravenous injection of N-methyl-N-nitrosourea and chronic intraperitoneal injections of four testosterone esters following surgical castration. Animals with an initial body weight of 328±39 g were randomized into 3 groups: experimental group (n=32) - animals received polyprenols complex 12.5 mg/kg per os diluted in vegetable oil 5 days a week; control group (n=38) - animals received vehicle (vegetable oil) 0.5 ml per os 5 days a week; intact group (n=12) - animals without intervention. Duration of the experiment was 56 weeks. At the end of the study and in euthanized animals in terminal state as well, the prostate and seminal vesicles were processed by histological technique and serial step sections of all lobes were assessed blindly by two independent pathologists. Incidence and multiplicity of precancerous lesion (PIN) and prostate tumors were calculated. Results. Compared with the control group, long-term consumption of polyprenols significantly reduced the overall incidence of PIN from 76.5 to 44.8% (р=0.0183; relative risk, RR=0.59; 95% CI 0.38-0.91), multiplicity of PIN per rat per group by 48.4% (р=0.0081), the incidence of PIN in 2 or 3 lobes of the prostate from 55.9 to 27.6% (р=0.0402), the incidence of PIN in the dorsolateral prostate from 70.6 to 41.4% (р=0.0240), the incidence of PIN in the ventral lobe from 47.1 to 20.7% (р=0.0362). The polyprenol complex exhibited a pronounced anticancer effect against induced prostate tumors. In the group of animals receiving the tested agent, there was a significant decrease in the total incidence of PCa from 64.7 to 34.5% (р=0.0234; RR=0.53; 95% CI 0.30-0.93), as well as the multiplicity of PCa per rat per group and per PIN carrier by 63.4% (р=0.0024) and by 30.6% (р=0.0240) respectively. In the polyprenols group we observed significant decrease in the incidence of prostate cancer in 2 or 3 lobes from 32.4 to 6.9% (р=0.0147) and the incidence of PCa in the dorsolateral prostate from 58.8 to 24.1% (р=0.0101). Oral administration of polyprenols provided a nonsignificant trend towards a decrease in the incidence of metastatic prostate cancer from 32.4 to 20.7% (р=0.3962). Conclusion. Chronic oral consumption of polyprenols from the needles of Picea abies L. and Pinus sylvestris L. (12.5 mg/kg per day) significantly suppresses the development of PIN and PCa induced by MNM and a mixture of testosterone esters in male Wistar rats. Despite the exploratory nature of the study, our results can serve the rationale for further investigation of polyprenols in prostate cancer chemoprevention trials.

Incidence of Metastatic Prostate Cancer On the Rise.

Incidence of Metastatic Prostate Cancer On the Rise.

Prostate-Specific Antigen Screening and Recent Increases in Advanced Prostate Cancer.

Recent studies show decreasing prostate-specific antigen utilization and increasing incidence of metastatic prostate cancer in the United States after national recommendations against screening in 2012. Yet, whether the increasing incidence of metastatic prostate cancer is consistent in magnitude with the expected impact of decreased screening is unknown. We compared observed incidence of metastatic prostate cancer from the Surveillance, Epidemiology, and End Results program and published effects of continued historical screening and discontinued screening starting in 2013 projected by 2 models of disease natural history, screening, and diagnosis. The observed rate of new metastatic prostate cancer cases in 2017 was 44%-60% of the projected increase under discontinued screening relative to continued screening. Thus, the observed increase in incident metastatic prostate cancer is consistent with the expected impact of reduced screening. Although this comparison does not establish a causal relationship, it highlights the plausible role of decreased screening in the observed trend.

An Up-to-date Assessment of US Prostate Cancer Incidence Rates by Stage and Race: A Novel Approach Combining Multiple Imputation with Age and Delay Adjustment

BackgroundIn the USA, it is unknown whether metastatic prostate cancer incidence has continued to increase and whether racial differences have persisted. ObjectiveCombining multiple imputation with age and delay adjustment, we provide an up-to-date, comprehensive assessment of US prostate cancer incidence trends by stage and race. Design, setting, and participantsFrom Surveillance Epidemiology and End Results (SEER)-18, 774 240 prostate cancer cases were diagnosed during 2004–2017. Outcome measurements and statistical analysisMultiple imputation assigned prostate cancer stage to the 4.7% of cases with missing stage, which varied by year and race-ethnicity. SEER delay factors adjusted case counts to anticipated future data corrections. Twenty datasets were imputed, and Rubin’s rules were used for summary estimation. Overall and stage-specific rates were estimated and stratified by race and age group. Joinpoint software identified significant temporal changes and estimated annual percentage changes. We compared these estimates without multiple imputation and delay adjustment. Results and limitationsMetastatic prostate cancer incidence increased during 2011–2017, with an annual percentage change of 5.5. This was followed by increases in localized and regional disease since 2014. Non-Hispanic black men continued to have the highest incidence, especially for metastatic disease. The increasing rate of metastatic prostate cancer in non-Hispanic white men aged 50–74 yr accelerated recently, and the incidence was 56% higher in 2017 than in 2004. Rates without multiple imputation and delay adjustment were quantitatively and qualitatively different. This observational study is unable to assign causes to observed changes in prostate cancer incidence. ConclusionsMultiple imputation and delay adjustment are essential for portraying accurately stage- and race-specific prostate cancer incidence as clinical practice evolves. Patient summaryIn the USA, diagnosis of prostate cancer that has spread to distant sites (metastatic disease) continues to increase. Black men continue to have higher risks of being diagnosed with metastatic prostate cancer than other race-ethnicities.

MP64-05 TRENDS IN INCIDENCE AND SURVIVAL AMONG MEN WITH METASTATIC PROSTATE CANCER: SEER ANALYSIS 2004-2015

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II (MP64)1 Apr 2020MP64-05 TRENDS IN INCIDENCE AND SURVIVAL AMONG MEN WITH METASTATIC PROSTATE CANCER: SEER ANALYSIS 2004-2015 Rehana Rasul, Anne Golden, and Michael Feuerstein* Rehana RasulRehana Rasul More articles by this author , Anne GoldenAnne Golden More articles by this author , and Michael Feuerstein*Michael Feuerstein* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000939.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since docetaxel was approved in 2004, several new drugs have been approved demonstrating efficacy and improved survival for metastatic prostate cancer patients. In the past decade prostate cancer screening has decreased, in part due to the USPSTF recommendation in 2012. This study evaluated the impact of these developments on population trends in metastatic prostate cancer incidence and survival. METHODS: Men ≥18 years diagnosed with de novo stage M1 prostate cancer from 2004-2015 were identified from SEER 18 Registries. M1 was classified as non-regional lymph nodes (M1a), bone metastasis with or without lymph nodes (M1b) and distant metastatic disease (M1c). Age-adjusted incidence rates per 100,000 were calculated. Unadjusted 2-year overall and prostate cancer mortality rates by year of diagnosis were calculated using the Kaplan Meier method. RESULTS: We identified 34,888 men with M1 prostate cancer with median age of 72 years. From 2004-2015, there was a slight increase in de novo M1 disease from 10.2 per 100,000 to 12.1 per 100,000 (Figure). M1b prostate cancer rates increased, while M1a and M1c rates remained stable. 2-year overall mortality for M1 disease decreased from 0.50 (±0.01) to 0.46 (±0.01) from 2004-2014, while 2-year prostate cancer mortality decreased from 0.40 (±0.01) to 0.37 (±0.01). CONCLUSIONS: As might be expected from decreased screening, there was an increase in diagnosis of de novo metastatic prostate cancer from 2004-2015. Population data also demonstrated a modest improvement in survival from 2004-2015. The survival trend may be less pronounced than expected due to decreased screening and later diffusion of effective treatments. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e964-e964 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rehana Rasul More articles by this author Anne Golden More articles by this author Michael Feuerstein* More articles by this author Expand All Advertisement PDF downloadLoading ...

Geographic-Level Association of Contemporary Changes in Localized and Metastatic Prostate Cancer Incidence in the Era of Decreasing PSA Screening.

Decreased prostate-specific antigen screening since 2008 has generated much concern, including report of recent increase in metastatic prostate cancer incidence among older men. Although increased metastatic disease was temporally proceeded by decreased screening and decreased localized prostate cancer at diagnosis, it is unclear whether the 2 trends are geographically connected. We therefore used the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database to assess geographic-specific associations between changes in localized (2008-2011) and later changes in metastatic prostate cancer incidence (2012-2015). We examined trends from 200 health-care service areas (HSAs) within SEER 18 registries. While on average for each HSA, localized incidence decreased by 27.4 and metastatic incidence increased by 2.3 per 100 000 men per year, individual HSA-level changes in localized incidence did not correlate with later changes in metastatic disease. Decreased detection of localized disease may not fully explain the recent increase in metastatic disease at diagnosis.