Prostate Cancer Mortality Research Articles

Umbrella Review on the Relationship between Vitamin D Levels and Cancer.

Cancer is a growing public health problem and cancer is linked to vitamin D via several mechanisms. Recent umbrella reviews on the extra-skeletal effects of vitamin D did not turn their attention to cancer. Accordingly, an overview of the current state of research is needed. An umbrella review was conducted to provide an overview of systematic reviews on the association between vitamin D and incidence or mortality of breast cancer, colorectal cancer, lung cancer, pancreatic cancer, and prostate cancer. Inverse correlations were found between the vitamin D level (measured by circulating 25(OH)D) and mortality for all five types of cancer. For breast cancer, colorectal cancer, lung cancer, and pancreatic cancer, there are also hints of a lower incidence due to higher 25(OH)D levels. As most reviews include observational studies, conclusions on causality cannot be made. Methodological differences between the included reviews and different study designs in the individual studies lead to methodological problems. Despite these problems, the review shows inverse correlations between 25(OH)D levels and mortality, and mostly inverse correlations between 25(OH)D levels and incidence.

PRMT5-mediated FUBP1 methylation accelerates prostate cancer progression.

Strategies beyond hormone-related therapy need to be developed to improve prostate cancer mortality. Here, we show that FUBP1 and its methylation were essential for prostate cancer progression, and a competitive peptide interfering with FUBP1 methylation suppressed the development of prostate cancer. FUBP1 accelerated prostate cancer development in various preclinical models. PRMT5-mediated FUBP1 methylation, regulated by BRD4, was crucial for its oncogenic effect and correlated with earlier biochemical recurrence in our patient cohort. Suppressed prostate cancer progression was observed in various genetic mouse models expressing the FUBP1 mutant deficient in PRMT5-mediated methylation. A competitive peptide, which was delivered through nanocomplexes, disrupted the interaction of FUBP1 with PRMT5, blocked FUBP1 methylation, and inhibited prostate cancer development in various preclinical models. Overall, our findings suggest that targeting FUBP1 methylation provides a potential therapeutic strategy for prostate cancer management.

The Impact of Radical Prostatectomy Versus Radiation Therapy on Cancer-Specific Mortality for Nonmetastatic Prostate Cancer: Analysis of an Other-Cause Mortality Matched Cohort

IntroductionStudies comparing radical prostatectomy (RP) to radiation therapy (RT) have consistently shown that patients undergoing RT have a higher risk of other-cause mortality (OCM) compared to RP, signifying poor health status of the former patients. We aimed to evaluate the impact of RP versus RT on cancer-specific mortality (CSM) over a cohort with equivalent OCM risk. Patients and MethodsThe SEER database was queried to identify patients with nonmetastatic PCa between 2004 and 2009. Patients were matched based on their calculated 10-year OCM risk and further stratified for D'Amico Risk Score and Gleason Grade. A Cox-regression model was used to calculate the 10-year OCM risk. Propensity-score based on the calculated OCM risk were used to match RP and RT patients. Cumulative incidence curves and Competing-risk regression analyses were used to examine the impact of treatment on CSM in the matched cohort. ResultsWe identified 55,106 PCa patients treated with RP and 36,674 treated with RT. After match, 6,506 patients were equally distributed for RT versus RP, with no difference in OCM rates (P = .2). The 10-year CSM rates were 8.8% versus 0.6% (P = .01) for RT versus RP in patients with unfavorable-intermediate-risk (Gleason Score 4 + 3) and 7.9% versus 3.9% (P = .003) for high-risk disease. There was no difference in CSM among RT and RP patients for favorable-intermediate-risk (Gleason Score 3 + 4) and low-risk disease. ConclusionsIn a matched cohort of PCa patients with comparable OCM between the 2 arms, RP yielded a more favorable CSM rate compared to RT only for unfavorable-intermediate- and high-risk groups.

Intratumoral vitamin D signaling and lethal prostate cancer.

High circulating vitamin D levels and supplementation may lower prostate cancer mortality. To probe for direct effects of vitamin D signaling in the primary tumor, we assessed how activation of intratumoral vitamin D signaling in prostate cancer is associated with lethal prostate cancer during long-term follow-up. Among 404 participants with primary prostate cancer in the Health Professionals Follow-up Study and the Physicians' Health Study, we defined a gene score of expected activated intratumoral vitamin D signaling consisting of transcriptionally upregulated (CYP27A1, CYP2R1, RXRA, RXRB, and VDR) and downregulated genes (CYP24A1 and DHCR7). We contrasted vitamin D signaling in tumors that progressed to lethal disease (metastases/prostate cancer-specific death, n = 119) over up to three decades of follow-up with indolent tumors that remained nonmetastatic for >8 years post-diagnosis (n = 285). The gene score was downregulated in tumor tissue compared with tumor-adjacent histologically normal tissue of the same men. Higher vitamin D gene scores were inversely associated with lethal prostate cancer (odds ratio for highest versus lowest quartile: 0.46, 95% confidence interval: 0.21-0.99) in a dose-response fashion and after adjusting for clinical and pathologic factors. This association appeared strongest among men with high predicted plasma 25-hydroxyvitamin D3 and men with body mass index ≥25 kg/m2. Findings were replicated with broader gene sets. These data support the hypothesis that active intratumoral vitamin D signaling is associated with better prostate cancer outcomes and provide further rationale for testing how vitamin D-related interventions after diagnosis could improve prostate cancer survival through effects on the tumor.

Prostate-Specific Antigen Screening and Prostate Cancer Mortality: An Emulation of Target Trials in US Medicare.

No consensus about the effectiveness of prostate-specific antigen (PSA) screening exists among clinical guidelines, especially for the elderly. Randomized trials of PSA screening have yielded different results, partly because of variations in adherence, and it is unlikely that new trials will be conducted. Our objective was to estimate the effect of annual PSA screening on prostate cancer (PC) mortality in Medicare beneficiaries age 67-84 years. This is a large-scale, population-based, observational study of two screening strategies: annual PSA screening and no screening. We used data from 537,599 US Medicare (2001-2008) beneficiaries age 67-84 years who had a good life expectancy, no previous PC, and no PSA test in the 2 years before baseline. We estimated the 8-year PC mortality and incidence, treatments for PC, and treatment complications of PSA screening. In men age 67-74 years, the estimated difference in 8-year risk of PC death between PSA screening and no screening was -2.3 (95% CI, -4.1 to -1.1) deaths per 1,000 men (a negative risk difference favors screening). Treatment complications were more frequent under PSA screening than under no screening. In men age 75-84 years, risk difference estimates were closer to zero. Our estimates suggest that under conventional statistical criteria, annual PSA screening for 8 years is highly compatible with reductions of PC mortality from four to one fewer PC deaths per 1,000 screened men age 67-74 years. As with any study using real-world data, the estimates could be affected by residual confounding.

Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes.

Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. Around 5,139 differentially methylated CpG-sites (q<0.01, lΔβl>0.2) were identified when comparing normal vs. tumor,with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors' total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG-sites (q<0.05, lΔβl>.05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA-C, and ADCYAP1, have previously been linked to tumor progression in PCa. Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.

The Incidence of Extreme Serum Prostate Specific Antigen Levels During the COVID-19 Pandemic

ObjectiveThe COVID-19 pandemic resulted in decreased prostate specific antigen (PSA) testing for prostate cancer screening and its impact remains uncharacterized. Our objective was to compare incident PSA testing rates, PSA levels, and prostate cancer treatment rates before and during the pandemic after the state of emergency (SoE) was declared. Materials and MethodsThis was a population-based, retrospective cohort study among men 50-80 years of age in Ontario, Canada undergoing incident PSA testing from November 23, 2018 to July 9, 2021. Working backwards and forwards from the date of the province-wide SoE (March 17, 2020), 30-day time periods were constructed during which incident PSA testing rates were measured. Our primary outcome was the rate of incident PSA testing. Secondary endpoints included comparison of incident PSA levels and prostate cancer treatment rates. ResultsWe identified 835,402 men who underwent incident PSA testing. There was a 20% decrease in PSA testing after the SoE (RR = 0.80,95% CI: 0.800.81, P < .001). There was a higher proportion of extreme PSA levels after the SoE with a higher proportion of patients with a PSA >20 ng/mL (rate ratio = 1.63,95% CI: 1.54-1.73, P < .0001) and >100 ng/mL (rate ratio = 1.98,95% CI: 1.77-2.20, P < .0001). This effect was highest for those aged 50-59 years. More patients required active treatment (5,201,59.5% prior to the pandemic vs. 5,072,64.2%, P < .001 after the SoE declaration). ConclusionsThe COVID-19 SoE resulted in patients experiencing a 2-fold increase in the risk of having an extreme PSA level and higher odds of treatment. Future studies are needed to assess the impact on the rates of advanced prostate cancer and cancer-specific mortality.

Management and Oncologic Outcomes of Incidental Prostate Cancer After Transurethral Resection of the Prostate in Denmark.

Approximately 1 in 10 patients without prior prostate biopsy undergoing surgery for lower urinary tract symptoms harbors incidental prostate cancer; however, practice guidelines do not provide recommendations for its management. We aimed at describing the oncologic outcomes of patients with Grade Group (GG) 1 and GG2 prostate cancer diagnosed at transurethral resection of the prostate (TURP). This was a nationwide, population-based, observational study of patients undergoing TURP in Denmark from 2006 to 2022 using the Danish Prostate Registry. We estimated the cumulative incidence of further biopsies and MRI, curative treatment, endocrine treatment, and cause-specific mortality with competing risk analyses. Among 24,494 patients who underwent TURP, there were 1016 men with GG1 and 381 with GG2 prostate cancer. The 5-year cumulative incidence of further MRIs or biopsies was 36% (95% CI 33%-39%) for GG1 and 30% (95% CI 25%-34%) for GG2 disease. Fifteen-year prostate cancer mortality was 8.4% (95% CI 5.3%-11%) for GG1 and 14% (7.5%-21%) for GG2. A total of 270 men with GG1 disease underwent a biopsy after the TURP, and 162 (60%) had no cancer; in this group, prostate cancer mortality after 15 years was 0.6% (95% CI 0%-1.8%). Men with post-TURP biopsy ≥ GG2 had a prostate cancer mortality of 30% (95% CI 9%-50%) 15 years post TURP. The major limitation was the heterogeneous follow-up, which could lead to an overestimation of prostate cancer mortality compared to a more standardized follow-up. We observed high prostate cancer mortality after TURP with GG1 or GG2, likely due to unsampled high-grade cancer in the peripheral zone. Patients with incidental prostate cancer should be further investigated to rule out high-grade cancer. For patients with GG1 on TURP, once a subsequent biopsy does not show cancer, follow-up should be lessened similar to that of patients with an initial nonmalignant biopsy.

Impact of Prostate-Specific Antigen Screening Pattern on Prostate Cancer Mortality Among Non-Hispanic Black and Non-Hispanic White Men: A Large, Urban Health System Cohort Analysis.

Randomized studies assessing the effect of PSA screening on mortality in non-Hispanic Black (NHB) men are lacking. We aimed to assess the association between PSA screening and survival among NHB men in comparison to non-Hispanic White (NHW) men in a racially diverse real-world North American population. The study cohort included 6378 men who self-identified as NHB or NHW and were diagnosed with prostate cancer (PCa). Patients received PSA screening and subsequent PCa treatment and follow-up at our institution. Patients were sorted based on PSA testing intensity for the 5 years prior to diagnosis, as follows: never, some (<1 test/y), and annual testing (1 test/y). The primary outcome was risk of prostate cancer-specific mortality (PCSM). Competing risk cumulative incidence curves estimated PCSM rates. Competing risk regression analyses examined the impact of PSA testing on PCSM. An interaction term was incorporated to assess the impact of race on the outcome. Median (IQR) age and PSA at diagnosis were 67 (60-73) years and 5.8 (4.4-9.6) ng/mL, respectively, and 2929 (46%) men were NHB (Kruskal-Wallis P values < .001). Annual PSA testing was more frequent in NHW (5%) than in NHB (3%) men (χ2 P value < .001). On cumulative incidence analysis, in the never, some, and annual PSA testing groups, the 10-year PCSM was respectively 12.3%, 5.8%, and 4.6% in NHW and 18.5%, 7%, and 1.2% in NHB patients (Gray's test P values < .001). At competing risk regression, PSA screening rate was associated with more favorable PCSM rates (HR: 0.47; 95% CI 0.33-0.68; P < .001). The interaction term for race did not show statistical significance (P = .2). PSA testing was associated with a reduced risk of PCSM in both NHB and NHW men diagnosed with PCa. Additionally, the positive impact of the screening rate seemed to be independent of race.

Effect of metformin on incidence, recurrence, and mortality in prostate cancer patients: integrating evidence from real-world studies.

Metformin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between metformin use and the risk of occurrence of prostate cancer (PCa). The purpose of this study was to assess the effect of metformin on clinical outcomes in patients with PCa in a meta-analysis and to explore the possible dose-response relationship. A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of metformin on the risk of PCa. Relevant subgroup analyses and sensitivity analyses were performed. The across studies results show that metformin use associated with lower incidence of PCa (RR: 0.82, 95% CI: 0.74-0.91). Metformin use was also found to reduce PCa recurrence, but the results were not statistically significant (RR: 0.97, 95% CI: 0.81-1.15). Metformin use was not associated with PCa mortality (RR: 0.94, 95% CI: 0.81-1.09). The results of subgroup analyses indicated that the type of study was a cohort study and the population came from both Asia and Europe showed that taking metformin reduced the incidence of PCa. A linear correlation was found between the duration of metformin use and its protective effect. This meta-analysis revealed an independent correlation between metformin use and reduced incidence of PCa. Metformin use was not associated with either PCa recurrence rate or mortality. Furthermore, the effect of metformin on PCa incidence was found to be related to duration.

Prostate Risk and Monitoring During Testosterone Replacement Therapy.

Men with hypogonadism have reduced risk of prostate cancer mortality; whether testosterone treatment increases the risk of prostate safety events in men with hypogonadism remains controversial. Several studies including 4 larger randomized trials-the Testosterone Trials, TEstosterone and Atherosclerosis Progression in Aging Men (TEAAM) trial, Testosterone for Diabetes Mellitus trial, and Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) trial-treated men with testosterone or placebo for 1 year or longer and reported prospectively ascertained prostate safety data. The TRAVERSE Trial, because of its large size, longer duration, and adjudication of prostate events, has provided comprehensive data on the risk of adverse prostate events during testosterone replacement therapy (TRT). Among men with hypogonadism, carefully screened to exclude those at high risk of prostate cancer, the incidences of high-grade or any prostate cancer, acute urinary retention, surgical procedure for benign prostatic hyperplasia, prostate biopsy, or new pharmacologic therapy for lower urinary tract symptoms were low and did not differ between the testosterone and placebo groups. Testosterone did not worsen lower urinary tract symptoms. TRT was associated with a greater increase in prostate-specific antigen than placebo in the first year of treatment. Testosterone treatment of men with hypogonadism, screened to exclude those at high risk of prostate cancer, is associated with low risk of adverse prostate events. Baseline evaluation of prostate cancer risk and a standardized monitoring plan can minimize the risk of unnecessary prostate biopsy while enabling the detection of high-grade prostate cancers in men receiving TRT.

Neighborhood Disadvantage and Prostate Tumor RNA Expression of Stress-Related Genes

African American men experience greater prostate cancer incidence and mortality than White men. Growing literature supports associations of neighborhood disadvantage, which disproportionately affects African American men, with aggressive prostate cancer; chronic stress and downstream biological impacts (eg, increased inflammation) may contribute to these associations. To examine whether several neighborhood disadvantage metrics are associated with prostate tumor RNA expression of stress-related genes. This cross-sectional study leveraged prostate tumor transcriptomic data for African American and White men with prostate cancer who received radical prostatectomy at the University of Maryland Medical Center between August 1992 and January 2021. Data were analyzed from May 2023 to April 2024. Using addresses at diagnosis, 2 neighborhood deprivation metrics (Area Deprivation Index [ADI] and validated bayesian Neighborhood Deprivation Index) as well as the Racial Isolation Index (RI) and historical redlining were applied to participants' addresses. Self-reported race was determined using electronic medical records. A total of 105 stress-related genes were evaluated with each neighborhood metric using linear regression, adjusting for race, age, and year of surgery. Genes in the Conserved Transcriptional Response to Adversity (CTRA) and stress-related signaling genes were included. A total of 218 men (168 [77%] African American, 50 [23%] White) with a median (IQR) age of 58 (53-63) years were included. African American participants experienced greater neighborhood disadvantage than White participants (median [IQR] ADI, 115 [100-130] vs 92 [83-104]; median [IQR] RI, 0.68 [0.34-0.87] vs 0.11 [0.06-0.14]). ADI was positively associated with expression for 11 genes; HTR6 (serotonin pathway) remained significant after multiple-comparison adjustment (β = 0.003; SE, 0.001; P < .001; Benjamini-Hochberg q value = .01). Several genes, including HTR6, were associated with multiple metrics. We observed higher expression of 5 proinflammatory genes in the CTRA with greater neighborhood disadvantage (eg, CXCL8 and ADI, β = 0.008; SE, 0.003; P = .01; q value = .21). In this cross-sectional study, the expression of several stress-related genes in prostate tumors was higher among men residing in disadvantaged neighborhoods. This study is one of the first to suggest associations of neighborhood disadvantage with prostate tumor RNA expression. Additional research is needed in larger studies to replicate findings and further investigate interrelationships of neighborhood factors, tumor biology, and aggressive prostate cancer to inform interventions to reduce disparities.

Absolute risk from double nested case-control designs: cause-specific proportional hazards models with and without augmented estimating equations.

We estimate relative hazards and absolute risks (or cumulative incidence or crude risk) under cause-specific proportional hazards models for competing risks from double nested case-control (DNCC) data. In the DNCC design, controls are time-matched not only to cases from the cause of primary interest, but also to cases from competing risks (the phase-two sample). Complete covariate data are available in the phase-two sample, but other cohort members only have information on survival outcomes and some covariates. Design-weighted estimators use inverse sampling probabilities computed from Samuelsen-type calculations for DNCC. To take advantage of additional information available on all cohort members, we augment the estimating equationswith a term that is unbiased for zero but improves the efficiency of estimates from the cause-specific proportional hazards model. We establish the asymptotic properties of the proposed estimators, including the estimator of absolute risk, and derive consistent variance estimators. We show that augmented design-weighted estimators are more efficient than design-weighted estimators. Through simulations, we show that the proposed asymptotic methods yield nominal operating characteristics in practical sample sizes. We illustrate the methods using prostate cancer mortality data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Study of the National Cancer Institute.

Variants in Vitamin D-related Genes and Prostate Cancer Risk in Black Men.

The relationship between vitamin D and prostate cancer has primarily been characterized among White men. However, Black men have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine six critical genes in the vitamin D pathway and prostate cancer risk in Black men. We assessed a total of 69 candidate variants in six genes ( GC, CYP27A1, CYP27B1, CYP24A1, VDR , and RXRA ) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide association study data for approximately 10,000 prostate cancer cases and 10,000 controls among Black men and over 85,000 cases and 91,000 controls among White men. A statistical significance threshold of 0.000724 was used to account for the 69 variants tested. None of the variants examined were significantly associated with prostate cancer risk among Black men after multiple comparison adjustment. Four variants tested P<0.05 in Black men, including two in RXRA (rs41400444 OR=1.09, 95% CI: 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.87-1.00, P = 0.046) and two in VDR (rs2853563 OR = 1.07, 1.01-1.13, P = 0.017 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.045). Two variants in VDR were also positively associated with risk in White men (rs11568820 OR = 1.04, 1.02-1.06, P = 0.00024 and rs4516035 OR = 1.03, 1.01-1.04, P = 0.00055). We observed suggestive non-significant associations between genetic variants in RXRA and VDR and prostate cancer risk in Black men. Future research exploring the relationship of vitamin D with cancer risk in Black men will need larger sample sizes to identify ancestry-specific variants relevant to risk in this population.

Racial disparity in prostate cancer: an outlook in genetic and molecular landscape.

Prostate cancer (PCa) incidence, morbidity, and mortality rates are significantly impacted by racial disparities. Despite innovative therapeutic approaches and advancements in prevention, men of African American (AA) ancestry are at a higher risk of developing PCa and have a more aggressive and metastatic form of the disease at the time of initial PCa diagnosis than other races. Research on PCa has underlined the biological and molecular basis of racial disparity and emphasized the genetic aspect as the fundamental component of racial inequality. Furthermore, the lower enrollment rate, limited access to national-level cancer facilities, and deferred treatment of AA men and other minorities are hurdles in improving the outcomes of PCa patients. This review provides the most up-to-date information on various biological and molecular contributing factors, such as the single nucleotide polymorphisms (SNPs), mutational spectrum, altered chromosomal loci, differential gene expression, transcriptome analysis, epigenetic factors, tumor microenvironment (TME), and immune modulation ofPCa racial disparities. This review also highlights future research avenues to explore the underlying biological factors contributing to PCa disparities, particularly in men of African ancestry.

Prostate Cancer Incidence and Mortality Linked to Metalworking Fluid Exposure: A Systematic Review and Meta-Analysis

Introduction: Prostate cancer is a significant health concern, and occupational exposures, including metalworking fluid (MWF) exposure, have been implicated as potential risk factors. This protocol outlines a systematic review and meta-analysis methodology to investigate the association between MWF exposure and prostate cancer risk among male workers. Methods: Eligible studies include cohort, case-control, and cross-sectional studies published until between 1990 and 2023 focusing on MWF exposure and prostate cancer risk in male workers. Two independent reviewers will screen studies, extract data using a standardized form, conduct a meta-analysis using random-effects models, and assess study quality using the Newcastle-Ottawa Scale. Heterogeneity will be assessed, and sensitivity analyses will be conducted to explore sources of bias. Results: Anticipated outcomes include a comprehensive list of eligible studies, a synthesized analysis using random-effects meta-analysis models to estimate the association between MWF exposure and prostate cancer risk, and a quality assessment report of included studies. Subgroup analyses based on MWF type, exposure duration, and study design will be performed to explore heterogeneity. Conclusion: This systematic review and meta-analysis protocol aim to provide robust evidence on the association between MWF exposure and prostate cancer risk among male workers. The anticipated findings will have implications for occupational health practices and may guide future research and intervention strategies.

Trends in genitourinary cancer mortality in the United States: analysis of the CDC-WONDER database 1999-2020.

Sociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States. Mortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban-rural status, and geographic region using a significance level of p < 0.05. Overall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3-4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West. Significant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.

Estimating the Effect of Radical Prostatectomy: Combining Data From the SPCG4 and PIVOT Randomized Trials With Contemporary Cohorts.

Two randomized trials (SPCG4 and PIVOT) have compared surgery to conservative management for localized prostate cancer. The applicability of these trials to contemporary practice remains uncertain. We aimed to develop an individualized prediction model for prostate cancer mortality comparing immediate surgery at a high-volume center to active surveillance. We determined whether the relative risk of prostate cancer mortality with surgery vs observation varied by baseline risk. We then used various estimates of relative risk to estimate 15-year mortality with and without surgery using, as a predictor, risk of biochemical recurrence calculated from a model. We saw no evidence that relative risk varied by baseline risk, supporting the use of a constant relative risk. Compared with observation, surgery was associated with negligible benefit for patients with Grade Group (GG) 1 disease (0.2% mortality reduction at 15 years) and small benefit for patients with GG2 with lower PSA and stage (≤5% mortality reduction). Benefit was greater (6%-9%) for patients with GG3 or GG4 though still modest, but effect estimates varied widely depending on choice of hazard ratio for surgery (6%-36% absolute risk reduction). Surgery should be avoided for men with low-risk (GG1) prostate cancer and for many men with GG2 disease. Surgical benefits are greater in men with higher-risk disease. Integration of findings with a life expectancy model will allow patients to make informed treatment decisions given their oncologic risk, risk of death from other causes, and estimated effects of surgery.

Androgen Deprivation Therapy and Outcomes After Radiation Therapy in Black Patients With Prostate Cancer

Prostate cancer in Black men compared with White men may be more sensitive to radiation therapy resulting in better outcomes in equal-access settings. The outcomes of androgen-deprivation therapy (ADT) vs radiation therapy itself remains uncharacterized. To quantify any outcome modification by receipt of ADT on the association between Black race and prostate cancer outcomes following radiation therapy. This was a retrospective, nationwide cohort study of Black and White patients treated in the US Veterans Healthcare system between 2000 and 2020 receiving definitive radiation for localized prostate cancer. Data were analyzed from January 2000 to December 2020. Patient self-identified race and use of ADT defined as any gonadotrophin-releasing hormone agonist or antagonist prescription within 6 months of radiation. Biochemical recurrence (BCR) from time of completion of radiation therapy (prostate-specific antigen nadir plus 2 ng/mL) and development of metastatic disease or prostate cancer mortality (PCSM) from time of recurrence. A total of 26 542 patients (8716 Black men with median [IQR] age of 64 [59-69] years and 17 826 White men with median [IQR] age of 67 [62-72] years) received definitive radiation therapy for nonmetastatic prostate cancer and had complete staging and follow-up data. A total of 5144 patients experienced BCR (3384 White and 1760 Black patients). The cumulative incidence of BCR at 10 years was not significantly different between Black and White men (1602 [22.14%] vs 3099 [20.13%], respectively) with multivariable hazard ratio (HR) of 1.03 (95% CI, 0.97-1.09; P = .33). In men receiving ADT, Black men had an HR for BCR of 0.90 (95% CI, 0.82-0.99; P = .03) compared with White men, and in men not receiving ADT, Black men had an HR of 1.13 (95% CI, 1.05-1.22; P = .002). Black race was associated with a decreased risk of developing metastatic disease (HR, 0.90; 95% CI, 0.82-0.98; P = .02) or PCSM (subdistribution HR, 0.72; 95% CI, 0.63-0.82; P < .001) from time of biochemical recurrence. Black patients treated with radiation appear to specifically benefit from the addition of ADT with regard to biochemical control. Additionally, BCR in Black men results in a lower rate of metastatic disease and death from prostate cancer. Future analyses of radiosensitivity in Black men should evaluate for the possibility of outcome modification by ADT.

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.