Healthy lifestyle and prostate cancer risk in the Million Veteran Program.

BACKGROUND: This study aims to assess the impact of healthy lifestyle on prostate cancer (PCa) risk in a diverse population. METHODS: Data for 281,923 men from the Million Veteran Program (MVP), a nationwide, health system-based cohort study, were analyzed. Self-reported information at enrollment included smoking status, exercise, diet, family history of PCa, and race/ethnicity. Body mass index (BMI) was obtained from clinical records. Genetic risk was assessed via a validated polygenic score. Cox proportional hazards models were used to assess associations with PCa outcomes. RESULTS: After accounting for ancestry, family history, and genetic risk, smoking was associated with an increased risk of metastatic PCa (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.64-2.02; p < 10-16) and fatal PCa (HR, 2.73; 95% CI, 2.36-3.25; p < 10-16). Exercise was associated with a reduced risk of fatal PCa (HR, 0.86; 95% CI, 0.76-0.98; p = .03). Higher BMI was associated with a slightly reduced risk of fatal PCa, and diet score was not independently associated with any end point. Association with exercise was strongest among those who had nonmetastatic PCa at MVP enrollment. Absolute reductions in the risk of fatal PCa via lifestyle factors were greatest among men of African ancestry (1.7% for nonsmokers vs. 6.1% for smokers) or high genetic risk (1.4% for nonsmokers vs. 4.3% for smokers). CONCLUSIONS: Healthy lifestyle is minimally related to the overall risk of developing PCa but is associated with a substantially reduced risk of dying from PCa. In multivariable analyses, both exercise and not smoking remain independently associated with reduced metastatic and fatal PCa.

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

Importance: 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. Objectives: To quantify any outcome modification by receipt of ADT on the association between Black race and prostate cancer outcomes following radiation therapy. Design, Setting, and Participants: 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. Exposure: Patient self-identified race and use of ADT defined as any gonadotrophin-releasing hormone agonist or antagonist prescription within 6 months of radiation. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.

Advancements in Urothelial Cancer Care: Optimizing Treatment for Your Patient.

The standard treatment paradigm for muscle invasive bladder cancer has been neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. However, efforts are ongoing to personalize treatment by incorporating biomarkers to better guide treatment selection. In addition, bladder preservation strategies are aimed at avoiding cystectomy in well-selected patients. Similarly, in the metastatic urothelial cancer space, the standard frontline treatment option of platinum-based chemotherapy has changed with the availability of data from EV-302 trial, making the combination of enfortumab vedotin (EV) and pembrolizumab the preferred first-line treatment option. Here, we examine the optimization of treatment intensity and sequencing, focusing on the challenges and opportunities associated with EV/pembrolizumab therapy, including managing toxicities and exploring alternative dosing approaches. Together, these articles provide a comprehensive overview of contemporary strategies in bladder cancer management, highlighting the importance of individualized treatment approaches, ongoing research, and multidisciplinary collaboration to improve patient outcomes in this complex disease landscape.

Agent orange exposure and prostate cancer risk in the million veteran program.

BACKGROUND: The US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk. PATIENTS AND METHODS: Participants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models. RESULTS AND INTERPRETATION: On univariable analysis, exposure to Agent Orange was not associated with increased PCa (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.06), metastatic PCa (HR: 0.98, 95% CI: 0.91-1.05, p = 0.55), or fatal PCa (HR: 0.94, 95% CI: 0.79-1.09, p = 0.41). When accounting for race/ethnicity and family history, Agent Orange exposure was independently associated with slightly increased risk of PCa (HR: 1.06, 95% CI: 1.04-1.09, <10-6) but not with metastatic PCa (HR: 1.07, 95% CI: 0.98-1.15, p = 0.10) or PCa death (HR: 1.02, 95% CI: 0.83-1.23, p = 0.09). Similar results were found when accounting for genetic risk. Agent Orange exposure history may not improve modern PCa risk stratification.

Adrenal-Permissive Germline HSD3B1 Allele and Prostate Cancer Outcomes.

Importance: The adrenal androgen-metabolizing 3ß-hydroxysteroid dehydrogenase-1 enzyme, encoded by the HSD3B1 gene, catalyzes the rate-limiting step necessary for synthesizing nontesticular testosterone and dihydrotestosterone production. The common adrenal-permissive HSD3B1(1245C) allele is responsible for encoding the 3ß-HSD1 protein with decreased susceptibility to degradation resulting in higher extragonadal androgen synthesis. Retrospective studies have suggested an association of the HSD3B1 adrenal-permissive homozygous genotype with androgen deprivation therapy resistance in prostate cancer. Objective: To evaluate differences in mortality outcomes by HSD3B1 genetic status among men with prostate cancer. Design, Setting, and Participants: This cohort study of patients with prostate cancer who were enrolled in the Million Veteran Program within the Veterans Health Administration (VHA) system between 2011 and 2023 collected genotyping and phenotyping information. Exposure: HSD3B1 genotype status was categorized as AA (homozygous adrenal-restrictive), AC (heterozygous adrenal-restrictive), or CC (homozygous adrenal-permissive). Main Outcomes and Measures: The primary outcome of this study was prostate cancer-specific mortality (PCSM), defined as the time from diagnosis to death from prostate cancer, censored at the date of last VHA follow-up. Secondary outcomes included incidence of metastases and PCSM in predefined subgroups. Results: Of the 5287 participants (median [IQR] age, 69 [64-74] years), 402 (7.6%) had the CC genotype, 1970 (37.3%) had the AC genotype, and 2915 (55.1%) had the AA genotype. Overall, the primary cause of death for 91 patients (1.7%) was prostate cancer. Cumulative incidence of PCSM at 5 years after prostate cancer diagnosis was higher among men with the CC genotype (4.0%; 95% CI, 1.7%-6.2%) compared with the AC genotype (2.1%; 95% CI, 1.3%-2.8%) and AA genotype (1.9%; 95% CI, 1.3%-2.4%) (P = .02). In the 619 patients who developed metastatic disease at any time, the cumulative incidence of PCSM at 5 years was higher among patients with the CC genotype (36.0%; 95% CI, 16.7%-50.8%) compared with the AC genotype (17.9%; 95% CI, 10.5%-24.7%) and AA genotype (18.5%; 95% CI, 12.0%-24.6%) (P = .01). Conclusions and Relevance: In this cohort study of US veterans undergoing treatment for prostate cancer at the VHA, the HSD3B1 CC genotype was associated with inferior outcomes. The HSD3B1 biomarker may help identify patients who may benefit from therapeutic targeting of 3ß-hydroxysteroid dehydrogenase-1 and the androgen-signaling axis.

Neighborhood Deprivation, Race and Ethnicity, and Prostate Cancer Outcomes Across California Health Care Systems.

Importance: Non-Hispanic Black (hereafter, Black) individuals experience worse prostate cancer outcomes due to socioeconomic and racial inequities of access to care. Few studies have empirically evaluated these disparities across different health care systems. Objective: To describe the racial and ethnic and neighborhood socioeconomic status (nSES) disparities among residents of the same communities who receive prostate cancer care in the US Department of Veterans Affairs (VA) health care system vs other settings. Design, Setting, and Participants: This cohort study obtained data from the VA Central Cancer Registry for veterans with prostate cancer who received care within the VA Greater Los Angeles Healthcare System (VA cohort) and from the California Cancer Registry (CCR) for nonveterans who received care outside the VA setting (CCR cohort). The cohorts consisted of all males with incident prostate cancer who were living within the same US Census tracts. These individuals received care between 2000 and 2018 and were followed up until death from any cause or censoring on December 31, 2018. Data analyses were conducted between September 2022 and December 2023. Exposures: Health care setting, self-identified race and ethnicity (SIRE), and nSES. Main Outcomes and Measures: The primary outcome was all-cause mortality (ACM). Cox proportional hazards regression models were used to estimate hazard ratios for associations of SIRE and nSES with prostate cancer outcomes in the VA and CCR cohorts. Results: Included in the analysis were 49 461 males with prostate cancer. Of these, 1881 males were in the VA cohort (mean [SD] age, 65.3 [7.7] years; 833 Black individuals [44.3%], 694 non-Hispanic White [hereafter, White] individuals [36.9%], and 354 individuals [18.8%] of other or unknown race). A total of 47 580 individuals were in the CCR cohort (mean [SD] age, 67.0 [9.6] years; 8183 Black individuals [17.2%], 26 206 White individuals [55.1%], and 13 191 individuals [27.8%] of other or unknown race). In the VA cohort, there were no racial disparities observed for metastasis, ACM, or prostate cancer-specific mortality (PCSM). However, in the CCR cohort, the racial disparities were observed for metastasis (adjusted odds ratio [AOR], 1.36; 95% CI, 1.22-1.52), ACM (adjusted hazard ratio [AHR], 1.13; 95% CI, 1.04-1.24), and PCSM (AHR, 1.15; 95% CI, 1.05-1.25). Heterogeneity was observed for the racial disparity in ACM in the VA vs CCR cohorts (AHR, 0.90 [95% CI, 0.76-1.06] vs 1.13 [95% CI, 1.04-1.24]; P = .01). No evidence of nSES disparities was observed for any prostate cancer outcomes in the VA cohort. However, in the CCR cohort, heterogeneity was observed for nSES disparities with ACM (AHR, 0.82; 95% CI, 0.80-0.84; P = .002) and PCSM (AHR, 0.86; 95% CI, 0.82-0.89; P = .007). Conclusions and Relevance: Results of this study suggest that racial and nSES disparities were wider among patients seeking care outside of the VA health care system. Health systems-related interventions that address access barriers may mitigate racial and socioeconomic disparities in prostate cancer.

Prostate Cancer Screening Uptake in Transgender Women.

Importance: There is no consensus in prostate-specific antigen (PSA) screening guidelines regarding transgender women despite their known prostate cancer risk. Objective: To identify factors associated with recent (within the last 2 years) PSA screening in transgender women compared with cisgender men. Design, Setting, and Participants: This case-control study used data from the 2018 and 2020 Behavioral Risk Factor Surveillance System (BRFSS) surveys to characterize rates of PSA screening for prostate cancer within the past 2 years and multivariable logistic regressions to characterize factors associated with recent screening among transgender women. The BRFSS program of the Centers for Disease Control and Prevention annually surveys over 400 000 US adults on behavioral risk factors, chronic illnesses, and use of preventive services. Respondents to the BRFSS who were cisgender men or transgender women 40 years or older and who had complete PSA testing responses and no prostate cancer history were included; 313 transgender women and 138 937 cisgender men met inclusion criteria. Matching was performed by age, race and ethnicity, educational level, employment, annual income, survey year, and cost barriers to care. Data were collected on November 2, 2022, and analyzed from November 2, 2022, to December 3, 2023. Main Outcomes and Measures: Rates of and factors associated with recent PSA screening in transgender women. Results: Among the 1275 participants included in the matched cohort (255 transgender women and 1020 cisgender men; 570 [44.7%] aged 55-69 years), recent PSA screening rates among transgender women and cisgender men aged 55 to 69 were 22.2% (n = 26) and 36.3% (n = 165), respectively; among those 70 years and older, these rates were 41.8% (n = 26) and 40.2% (n = 98), respectively. In the matched cohort, transgender women had lower univariable odds of recent screening than cisgender men (odds ratio [OR], 0.65 [95% CI, 0.46-0.92]; P = .02). In a hierarchical regression analysis adding time since the last primary care visit, effect size and significance were unchanged (OR, 0.61 [95% CI, 0.42-0.87]; P = .007). After adding whether a clinician recommended a PSA test, there was no statistically significant difference in odds of screening between transgender women and cisgender men (OR, 0.83 [95% CI, 0.45-1.27]; P = .21). The results were further attenuated when clinician-led discussions of PSA screening advantages and disadvantages were added (OR, 0.87 [95% CI, 0.47-1.31]; P = .32). In a multivariable logistic regression among transgender women, having a recommendation for PSA testing was the factor with the strongest association with recent screening (OR, 12.40 [95% CI, 4.47-37.80]; P < .001). Conclusions and Relevance: In this case-control study of one of the largest cohorts of transgender women studied regarding PSA screening, the findings suggest that access to care or sociodemographic factors were not principal drivers of the screening differences between transgender women and cisgender men; rather, these data underscore the clinician's role in influencing PSA screening among transgender women.

Comparison of outcomes for Hispanic and non-Hispanic patients with advanced renal cell carcinoma in the International Metastatic Renal Cell Carcinoma Database.

BACKGROUND: Existing data on the impact of Hispanic ethnicity on outcomes for patients with renal cell carcinoma (RCC) is mixed. The authors investigated outcomes of Hispanic and non-Hispanic White (NHW) patients with advanced RCC receiving systemic therapy at large academic cancer centers using the International Metastatic Renal Cell Carcinoma Database (IMDC). METHODS: Eligible patients included non-Black Hispanic and NHW patients with locally advanced or metastatic RCC initiating systemic therapy. Overall survival (OS) and time to first-line treatment failure (TTF) were calculated using the Kaplan-Meier method. The effect of ethnicity on OS and TTF were estimated by Cox regression hazard ratios (HRs). RESULTS: A total of 1563 patients (181 Hispanic and 1382 NHW) (mostly males [73.8%] with clear cell RCC [81.5%] treated with tyrosine kinase inhibitor [TKI] monotherapy [69.9%]) were included. IMDC risk groups were similar between groups. Hispanic patients were younger at initial diagnosis (median 57 vs. 59 years, p = .015) and less likely to have greater than one metastatic site (60.8% vs. 76.8%, p < .001) or bone metastases (23.8% vs. 33.4%, p = .009). Median OS and TTF was 38.0 months (95% confidence interval [CI], 28.1-59.2) versus 35.7 months (95% CI, 31.9-39.2) and 7.8 months (95% CI, 6.2-9.0) versus 7.5 months (95% CI, 6.9-8.1), respectively, in Hispanic versus NHW patients. In multivariable Cox regression analysis, no statistically significant differences were observed in OS (adjusted hazard ratio [HR], 1.07; 95% CI, 0.86-1.31, p = .56) or TTF (adjusted HR, 1.06; 95% CI, 0.89-1.26, p = .50). CONCLUSIONS: The authors did not observe statistically significant differences in OS or TTF between Hispanic and NHW patients with advanced RCC. Receiving treatment at tertiary cancer centers may mitigate observed disparities in cancer outcomes.

Genetic risk and likelihood of prostate cancer detection on first biopsy by ancestry.

Despite differences in prostate cancer risk across ancestry groups, relative performance of prostate cancer genetic risks scores (GRS) for positive biopsy prediction in different ancestry groups is unknown. This cross-sectional retrospective analysis examines the association between a polygenic hazard score (PHS290) and risk of prostate cancer diagnosis upon first biopsy in male veterans using 2-sided tests. Our analysis included 36 717 veterans (10 297 of African ancestry). Unadjusted rates of positive first prostate biopsy increased with higher genetic risk (low risk: 34%, high risk: 58%; P < .001). Among men of African ancestry, higher genetic risk was associated with increased prostate cancer detection on first biopsy (odds ratio = 2.18, 95% confidence interval = 1.93 to 2.47), but the effect was stronger among men of European descent (odds ratio = 3.89, 95% confidence interval = 3.62 to 4.18). These findings suggest that incorporating genetic risk into prediction models could better personalize biopsy decisions, although further study is needed to achieve equitable genetic risk stratification among ancestry groups.

Effects of Androgen Deprivation Therapy on Prostate Cancer Outcomes According to Competing Event Risk: Secondary Analysis of a Phase 3 Randomised Trial.

BACKGROUND: Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks. OBJECTIVE: To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT. DESIGN, SETTING, AND PARTICIPANTS: An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted. INTERVENTION: Short-term ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score. RESULTS AND LIMITATIONS: T2b, higher GS, and higher PSA were associated with an increased RR for cancer-related versus competing mortality events (a higher omega score); increased age and comorbidity were associated with a decreased omega score. Of 996 patients with low-risk/favourable intermediate-risk (FIR) disease, 286 (28.7%) had a high omega score (≥0.314). Of 768 patients with unfavourable intermediate-risk disease, 175 (22.8%) had a low omega score. The overall discordance in risk classification was 26.1%. Both standard criteria and omega score identified significant interactions for the effect of ADT on cancer-related events and late mortality in low- versus high-risk subgroups. Within the low-risk/FIR subgroup, a higher omega score identified patients in whom ADT significantly reduced cancer events and improved event-free survival. Limitations are the need for external/prospective validation and lower RT doses than contemporary standards. CONCLUSIONS: Stratification based on competing event risk is useful for identifying prostate cancer patients who selectively benefit from ADT. PATIENT SUMMARY: We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer versus noncancer events. Among patients with traditional low-risk/favourable intermediate-risk disease, those with a higher RR benefitted from short-term ADT.

Association between prediagnostic prostate-specific antigen and prostate cancer probability in Black and non-Hispanic White men.

BACKGROUND: Although Black men are more likely than non-Hispanic White men to develop and die from prostate cancer, limited data exist to guide prostate-specific antigen (PSA) screening protocols in Black men. This study investigated whether the risk for prostate cancer was higher than expected among self-identified Black than White veterans based on prebiopsy PSA level. METHODS: Multivariable logistic regression models were estimated to predict the likelihood of prostate cancer diagnosis on first biopsy for 75,295 Black and 207,658 White male veterans. Self-identified race, age at first PSA test, prebiopsy PSA, age at first biopsy, smoking status, statin use, and socioeconomic factors were used as predictors. The adjusted predicted probabilities of cancer detection on first prostate biopsy from the logistic models at different PSA levels were calculated. RESULTS: After controlling for PSA and other covariates, Black veterans were 50% more likely to receive a prostate cancer diagnosis on their first prostate biopsy than White veterans (odds ratio [OR], 1.50; 95% CI, 1.47-1.53; p < .001). At a PSA level of 4.0 ng/mL, the probability of prostate cancer for a Black man was 49% compared with 39% for a White man. This model indicated that Black veterans with a PSA of 4.0 ng/mL have an equivalent risk of prostate cancer as White veterans with a PSA of 13.4 ng/mL. CONCLUSIONS: The findings indicate that, at any given PSA level, Black men are more likely to harbor prostate cancer than White men. Prospective studies are needed to better evaluate risks and benefits of PSA screening in Black men and other high-risk populations.

Opioid tapering in older cancer survivors does not increase psychiatric or drug hospitalization rates.

BACKGROUND: Opioid tapering in the general population is linked to increases in hospitalizations or emergency department visits related to psychiatric or drug-related diagnoses. Cancer survivors represent a unique population with different opioid indications, prescription patterns, and more frequent follow-up care. This study sought to describe patterns of opioid tapering among older cancer survivors and to test the hypothesis of whether older cancer survivors face increased risks of adverse events with opioid tapering. METHODS: Using the Surveillance, Epidemiology and End Results Medicare-linked database, we identified 15 002 Medicare-beneficiary cancer survivors diagnosed between 2010 and 2017 prescribed opioids consistently for at least 6 months after their cancer diagnosis. Tapering was defined as a binary time-varying event occurring with any monthly oral morphine equivalent reduction of 15% or more from the previous month. Primary diagnostic billing codes associated with emergency room or hospital admissions were used for the composite endpoint of psychiatric- or drug-related event(s). RESULTS: There were 3.86 events per 100 patient-months, with 97.8% events being mental health emergencies, 1.91% events being overdose emergencies, and 0.25% involving both. Using a generalized estimating equation for repeated measure time-based analysis, opioid tapering was not statistically associated with acute events in the 3-month posttaper period (odds ratio [OR] = 1.02; P = .62) or at any point in the future (OR = 0.96; P = .46). CONCLUSIONS: Opioid tapering in older cancer survivors does not appear to be linked to a higher risk of acute psychiatric- or drug-related events, in contrast to prior research in the general population.

Comparison of Capture Rates of the National Cancer Database Across Race and Ethnicity.

Importance: The National Cancer Database (NCDB) is an invaluable and widely used resource for cancer research, but the current state of representation of different racial and ethnic groups compared with the United States Cancer Statistics (USCS) database is unknown. Objective: To examine whether Hispanic and American Indian or Alaska Native individuals have lower representation in the NCDB compared with the USCS database. Design, Setting, and Participants: This multicenter, retrospective cohort study assessed individuals diagnosed with breast, colorectal, lung, and prostate cancer from January 1, 2004, to December 31, 2006, and January 1, 2017, to December 31, 2019, in the NCDB and USCS databases. Data analysis was performed from September 2022 to October 2023. Exposure: Time. Main Outcomes and Measures: The primary outcome was the absolute percentage change (APC) in capture rate across the study period. Results: The cohort included 5 175 007 individuals (0.50% American Indian or Alaska Native, 3.10% Asian or Pacific Islander, 12.01% Black, 6.58% Hispanic, and 77.81% White) who were diagnosed with breast, colorectal, lung, and prostate cancer. Capture rates were the lowest for individuals who were Hispanic (40.83% in 2004-2006 and 54.75% in 2017-2019; P < .001) or American Indian or Alaska Native (20.72% in 2004-2006 and 41.41% in 2017-2019; P < .001). The APCs were positive for both racial categories across all 4 cancers. However, overall APCs for Hispanic individuals (13.92%) remained lower than the overall APCs of White individuals (22.23%; P < .001). The APCs were greater for American Indian or Alaska Native individuals than for White individuals for prostate (14.68% vs 11.57%) and breast (21.61% vs 17.90%) cancer (P < .001), but the APCs for American Indian or Alaska Native individuals were lower than for White individuals for lung cancer (24.54% vs 33.03%; P < .001). Conclusions and Relevance: In this cohort study of individuals diagnosed with cancer in the NCDB, Hispanic and American Indian or Alaska Native individuals diagnosed with breast, colorectal, lung, and prostate cancer were undercaptured in the NCDB, but their representation improved over time. Increased study is needed to determine where these populations predominantly seek cancer care.

Agent Orange exposure and prostate cancer risk in the Million Veteran Program.

Purpose: Exposure to Agent Orange, a known carcinogen, might increase risk of prostate cancer (PCa). We sought to investigate the association of Agent Orange exposure and PCa risk when accounting for race/ethnicity, family history, and genetic risk in a diverse population of US Vietnam War veterans. Methods & Materials: This study utilized the Million Veteran Program (MVP), a national, population-based cohort study of United States military veterans conducted 2011-2021 with 590,750 male participants available for analysis. Agent Orange exposure was obtained using records from the Department of Veterans Affairs (VA) using the US government definition of Agent Orange exposure: active service in Vietnam while Agent Orange was in use. Only veterans who were on active duty (anywhere in the world) during the Vietnam War were included in this analysis (211,180 participants). Genetic risk was assessed via a previously validated polygenic hazard score calculated from genotype data. Age at diagnosis of any PCa, diagnosis of metastatic PCa, and death from PCa were assessed via Cox proportional hazards models. Results: Exposure to Agent Orange was associated with increased PCa diagnosis (HR 1.04, 95% CI 1.01-1.06, p=0.003), primarily among Non-Hispanic White men (HR 1.09, 95% CI 1.06- 1.12, p<0.001). When accounting for race/ethnicity and family history, Agent Orange exposure remained an independent risk factor for PCa diagnosis (HR 1.06, 95% CI 1.04-1.09, p<0.05). Univariable associations of Agent Orange exposure with PCa metastasis (HR 1.08, 95% CI 0.99-1.17) and PCa death (HR 1.02, 95% CI 0.84-1.22) did not reach significance on multivariable analysis. Similar results were found when accounting for polygenic hazard score. Conclusions: Among US Vietnam War veterans, Agent Orange exposure is an independent risk factor for PCa diagnosis, though associations with PCa metastasis or death are unclear when accounting for race/ethnicity, family history, and/or polygenic risk.

Low-Value Prostate-Specific Antigen Screening in Older Males.

Importance: The US Preventive Services Task Force guidelines advise against prostate-specific antigen (PSA) screening for prostate cancer in males older than 69 years due to the risk of false-positive results and overdiagnosis of indolent disease. However, this low-value PSA screening in males aged 70 years or older remains common. Objective: To characterize the factors associated with low-value PSA screening in males 70 years or older. Design, Setting, and Participants: This survey study used data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a nationwide annual survey conducted by the Centers for Disease Control and Prevention that collects information via telephone from more than 400 000 US adults on behavioral risk factors, chronic illnesses, and use of preventive services. The final cohort comprised male respondents to the 2020 BRFSS survey who were categorized into the following age groups: 70 to 74 years, 75 to 79 years, or 80 years or older. Males with a former or current prostate cancer diagnosis were excluded. Main Outcomes and Measures: The outcomes were recent PSA screening rates and factors associated with low-value PSA screening. Recent screening was defined as PSA testing within the past 2 years. Weighted multivariable logistic regressions and 2-sided significance tests were used to characterize factors associated with recent screening. Results: The cohort included 32 306 males. Most of these males (87.6%) were White individuals, whereas 1.1% were American Indian, 1.2% were Asian, 4.3% were Black, and 3.4% were Hispanic individuals. Within this cohort, 42.8% of respondents were aged 70 to 74 years, 28.4% were aged 75 to 79 years, and 28.9% were 80 years or older. The recent PSA screening rates were 55.3% for males in the 70-to-74-year age group, 52.1% in the 75-to-79-year age group, and 39.4% in the 80-year-or-older group. Among all racial groups, non-Hispanic White males had the highest screening rate (50.7%), and non-Hispanic American Indian males had the lowest screening rate (32.0%). Screening increased with higher educational level and annual income. Married respondents were screened more than unmarried males. In a multivariable regression model, discussing PSA testing advantages with a clinician (odds ratio [OR], 9.09; 95% CI, 7.60-11.40; P < .001) was associated with increased recent screening, whereas discussing PSA testing disadvantages had no association with screening (OR, 0.95; 95% CI, 0.77-1.17; P = .60). Other factors associated with a higher screening rate included having a primary care physician, a post-high school educational level, and income of more than $25 000 per year. Conclusions and Relevance: Results of this survey study suggest that older male respondents to the 2020 BRFSS survey were overscreened for prostate cancer despite the age cutoff for PSA screening recommended in national guidelines. Discussing the benefits of PSA testing with a clinician was associated with increased screening, underscoring the potential of clinician-level interventions to reduce overscreening in older males.

Associations Between Intraductal Prostate Cancer and Metastases Following Radical Prostatectomy in Men With Prostate Cancer in the Veterans Affairs Database.

PURPOSE: Intraductal carcinoma of the prostate (IDC-P) is a relatively unstudied feature present in some prostate cancer (PC) diagnoses with several studies suggesting associations with higher Gleason scores (GS) and earlier time to biochemical recurrence (BCR) after definitive treatment. We looked to identify cases of IDC-P in the Veterans Health Administration (VHA) database and measure associations between IDC-P and pathological stage, BCR, and metastases. METHODS: Patients in the VHA database diagnosed with PC from 2000 to 2017, treated with radical prostatectomy (RP) at the VHA were included in the cohort. BCR was defined as post-RP PSA >0.2 or administration of androgen deprivation therapy (ADT). Time to event was defined as time from RP to event or censor. Differences in cumulative incidences were assessed through Gray's test. Associations with IDC-P and pathologic features at RP, BCR and metastases were assessed through multivariable logistic and Cox regression models. RESULTS: Of 13,913 patients meeting inclusion criteria, 45 patients had IDC-P. Median follow up was 8.8 years from RP. Multivariable logistic regressions showed patients with IDC-P were more likely to have GS ≥8 (Odds Ratio (OR) 1.14, P = .009) and higher T stages (T3 or 4 vs. T1 or 2 OR 1.14, P < .001). In total, 4,318 patients experienced a BCR, and 1,252 patients developed metastases of whom 26 and 12, respectively, had IDC-P. On multivariable regression IDC-P was associated with higher risk of BCR (IDC-P Hazard Ratio (HR) 1.71, P = .006) and metastases (HR 2.84, P < .001). Cumulative incidence of metastases at 4 years for IDC-P and non-IDC-P were 15.9% and 5.5% (P < .001) respectively. CONCLUSIONS: In this analysis, IDC-P was associated with higher Gleason score at RP, shorter time to BCR, and higher rates of metastases. Further studies are warranted to investigate the molecular underpinnings of IDC-P to better guide treatment strategies for this aggressive disease entity.

Prognostic Value of the Intermediate-risk Feature in Men with Favorable Intermediate-risk Prostate Cancer: Implications for Active Surveillance.

Background: Guidelines suggest that active surveillance (AS) may be considered for select patients with favorable intermediate-risk (fIR) prostate cancer. Objective: To compare the outcomes between fIR prostate cancer patients included by Gleason score (GS) or prostate-specific antigen (PSA). Most patients are classified with fIR disease due to either a 3 + 4 = 7 GS (fIR-GS) or a PSA level of 10-20 ng/ml (fIR-PSA). Previous research suggests that inclusion by GS 7 may be associated with worse outcomes. Design setting and participants: We conducted a retrospective cohort study of US veterans diagnosed with fIR prostate cancer from 2001 to 2015. Outcome measurements and statistical analysis: We compared the incidence of metastatic disease, prostate cancer-specific mortality (PCSM), all-cause mortality (ACM), and receipt of definitive treatment between fIR-PSA and fIR-GS patients managed with AS. Outcomes were compared with those of a previously published cohort of patients with unfavorable intermediate-risk disease using cumulative incidence function and Gray's test for statistical significance. Results and limitations: The cohort included 663 men; 404 had fIR-GS (61%) and 249 fIR-PSA (39%). There was no evidence of difference in the incidence of metastatic disease (8.6% vs 5.8%, p = 0.77), receipt of definitive treatment (77.6% vs 81.5%, p = 0.43), PCSM (5.7% vs 2.5%, p = 0.274), and ACM (16.8% vs 19.1%, p = 0.14) between the fIR-PSA and fIR-GS groups at 10 yr. On multivariate regression, unfavorable intermediate-risk disease was associated with higher rates of metastatic disease, PCSM, and ACM. Limitations included varying surveillance protocols. Conclusions: There is no evidence of difference in oncological and survival outcomes between men with fIR-PSA and fIR-GS prostate cancer undergoing AS. Thus, presence of GS 7 disease alone should not exclude patients from consideration of AS. Shared decision-making should be utilized to optimize management for each patient. Patient summary: In this report, we compared the outcomes of men with favorable intermediate-risk prostate cancer in the Veterans Health Administration. We found no significant difference between survival and oncological outcomes.

Actionable Genomic Alterations in Prostate Cancer Among Black and White United States Veterans.

Black Veterans have higher a incidence of localized and metastatic prostate cancer compared to White Veterans yet are underrepresented in reports of frequencies of somatic and germline alterations. This retrospective analysis of somatic and putative germline alterations was conducted in a large cohort of Veterans with prostate cancer (N = 835 Black, 1613 White) who underwent next generation sequencing through the VA Precision Oncology Program, which facilitates molecular testing for Veterans with metastatic cancer. No differences were observed in gene alterations for FDA approved targetable therapies (13.5% in Black Veterans vs. 15.5% in White Veterans, P = .21), nor in any potentially actionable alterations (25.5% vs. 28.7%, P =.1). Black Veterans had higher rates of BRAF (5.5% vs. 2.6%, P < .001) alterations, White Veterans TMPRSS2 fusions (27.2% vs. 11.7%, P < .0001). Putative germline alteration rates were higher in White Veterans (12.0% vs. 6.1%, P < .0001). Racial disparities in outcome are unlikely attributable to acquired somatic alterations in actionable pathways.

Androgen deprivation therapy and acute kidney injury in patients with prostate cancer undergoing definitive radiotherapy.

BACKGROUND: Androgen deprivation therapy (ADT) is frequently utilized in conjunction with radiotherapy (RT) in the definitive management of prostate cancer. Prior studies have suggested an association between ADT use and acute kidney injury (AKI), however, these included heterogeneous populations undergoing a variety of treatments and relied on billing codes to ascertain the incidence of AKI. METHODS: We analyzed a cohort of 27,868 veterans undergoing definitive RT + /- ADT for prostate cancer between 2001 and 2015 using the Veterans Affairs Informatics and Computing Infrastructure (VINCI). Exposure was defined as use of ADT within one year of diagnosis. The primary outcome was AKI, defined by an increase in serum creatinine to at least 1.5 times the baseline value. AKIs were classified as mild, moderate, or severe in accordance with international guidelines. A multivariate competing risks model was used to account for demographic and oncologic factors as well as medications and procedures known to influence the risk of AKI. RESULTS: Most (n = 18,754) men received RT alone; 9,114 men received RT + ADT. The incidence of AKI at two years after diagnosis was 10.5% in the RT + ADT group and 7.9% in the RT group (Gray's test p < 0.01). Multivariate analysis confirmed ADT usage was associated with an increased risk for any AKI (SHR = 1.24, 95% CI = 1.14-1.36, p < 0.01). ADT was also associated with an increased risk of mild AKI (SHR = 1.13, 95% CI = 1.01-1.27, p = 0.04) and moderate AKI (SHR = 1.45, 95% CI = 1.20-1.76, p < 0.01), though not severe AKI (SHR = 1.33, 95% CI = 0.93-1.91, p = 0.11). CONCLUSIONS: Our findings confirm that use of ADT is associated with an increased risk of AKI in patients undergoing definitive RT for prostate cancer. Clinicians should be alert to the potential for renal dysfunction in this population.