Reducing Racial Inequalities in Prostate Cancer Treatment: Healthcare Access Barriers.

Inequalities in healthcare for patients with prostate cancer can result in treatment and mortality disparities. Despite Black men with prostate cancer having higher incidence and mortality from prostate cancer, the study by Hammarlund and colleagues found that they are less likely to receive appropriate treatment compared with their White counterparts. Given that Black men with prostate cancer have similar or better survival when participating in clinical trials or receiving equal treatment from an equal access to healthcare system, identifying factors contributing to inequitable treatment is essential to improve the overall health and survival of Black men with prostate cancer. See related article by Hammarlund and colleagues, Cancer Epidemiol Biomarkers Prev 2024;33:435-41.

Epidemiology, treatment patterns, and clinical outcomes in de novo oligometastatic hormone-sensitive prostate cancer.

BACKGROUND: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone-sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. METHODS: In this observational retrospective cohort study, 400 de novo metastatic hormone-sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow-up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan-Meier methods estimated overall survival (OS) and castration-resistant prostate cancer (CRPC)-free survival from mHSPC diagnosis date and a log-rank test compared these outcomes by oligometastatic status. RESULTS: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non-omHSPC had higher median prostate-specific antigen at diagnosis (151.7) than omHSPC (44.1). First-line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non-omHSPC (14%). More omHSPC patients received metastasis-directed therapy/prostate radiation therapy (14%) versus non-omHSPC (2%). Median OS and CRPC-free survival (in months) were higher in omHSPC versus non-omHSPC (44.4; 95% confidence interval [CI], 33.9-not estimated vs. 26.2; 95% CI, 20.5-32.5, p = .0089 and 27.6; 95% CI, 22.1-37.2 vs. 15.3; 95% CI, 12.8-17.9, p = .0049), respectively. CONCLUSIONS: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non-omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non-omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies.

Prostate-Specific Antigen Values in Transgender Women Receiving Estrogen.

This study examines prostate-specific antigen values among transgender women in the Veterans Health Administration receiving estrogen.

Metabolic Response to Androgen Deprivation Therapy of Prostate Cancer.

Prostate cancer (PC) stands as the most frequently diagnosed non-skin cancer and ranks as the second highest cause of cancer-related deaths among men in the United States. For those facing non-metastatic PC necessitating intervention, solely local treatments may not suffice, leading to a possible transition toward systemic therapies, including androgen deprivation therapy (ADT), chemotherapy, and therapies targeting androgen. Yet, these systemic treatments often bring about considerable adverse effects. Additionally, it is observed that overweight men are at a higher risk of developing aggressive forms of PC, advancing to metastatic stages, and succumbing to the disease. Consequently, there is a pressing demand for new treatment options that carry fewer side effects and enhance the current standard treatments, particularly for the majority of American men who are overweight or obese. In this article, we will review the metabolic response to ADT and how lifestyle modulation can mitigate these ADT-associated metabolic responses with a particular focus on the two clinical trials, Carbohydrate and Prostate Study 1 (CAPS1) and Carbohydrate and Prostate Study 2 (CAPS2), which tested the effects of low-carbohydrate diets on the metabolic side effects of ADT and PC progression, respectively. Furthermore, we will summarize the findings of serum metabolomic studies to elucidate the potential mechanisms by which ADT and low-carbohydrate diets can affect the metabolic response to mitigate the metabolic side effects while maximizing therapeutic efficacy.

Patient Perceptions of Standardized Risk Language Used in American College of Radiology Prostate MRI PIRADS Scores.

INTRODUCTION: Prostate MRI reports utilize standardized language to describe risk of clinically significant prostate cancer(csPCa) from "equivocal"(PI-RADS 3), "likely"(PI-RADS 4), to "highly-likely"(PI-RADS 5). These terms correspond to risks of 11%, 37%, and 70% according to AUA guidelines, respectively. We assessed how men perceive risk associated with standardized PI-RADS language. METHODOLOGY: We conducted a crowdsourced survey of 1,204 men matching a US prostate cancer demographic. We queried participants' risk perception associated with standardized PI-RADS language across increasing contexts: words-only, PI-RADS-sentence, full-report, and full-report-with-numeric-estimate. Median perceived risk (IQR) and absolute under/overestimation compared with AUA standards were reported. Multivariable linear mixed effects analysis identified factors associated with accuracy of risk perception. RESULTS: Median perceived risks of csPCa (IQR) for the word-only context were "equivocal" 50%(50-74), "likely" 75%(68-85), and "highly-likely" 87%(78-92), corresponding to +39%, +38%, +17% overestimation, respectively. Median perceived risks for the PI-RADS-sentence context were 50%(50-50), 75%(68-81), and 90%(80-94) for PI-RADS 3,4,and 5, corresponding to +39%, +38%, +20% overestimation, respectively. Median perceived risks for the full-report context were 50%(35-70), 72%(50-80), and 84%(54-91) for PI-RADS 3,4,and 5, corresponding to +39%, +35%, +14% overestimation, respectively. For the full-report-with-numeric-estimate context describing a PI-RADS 4 lesion, median perceived risk was 70%(50-80), corresponding to +33% overestimation. Including numeric estimates increased correct perception of risk from 3% to 11% (p<0.001), driven by men with higher numeracy (OR1.24,p=0.04). CONCLUSION: Men overestimate risk of csPCa associated with standardized PI-RADS language regardless of context, especially for PI-RADS 3 and 4 lesions. Changes to PI-RADS language or data sharing policies for imaging reports should be considered.

ONECUT2 acts as a lineage plasticity driver in adenocarcinoma as well as neuroendocrine variants of prostate cancer.

Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic inhibition of OC2 suppresses lineage plasticity reprogramming induced by the AR signaling inhibitor enzalutamide. These results demonstrate that OC2 activation promotes a range of drug resistance mechanisms associated with treatment-emergent lineage variation in PC and support enhanced efforts to therapeutically target OC2 as a means of suppressing treatment-resistant disease.

Challenges and Opportunities in Establishing Appropriate Intermediate Endpoints Reflecting Patient Benefit: A Roadmap for Research and Clinical Application in Nonmetastatic Prostate Cancer.

Defining meaningful endpoints for research of early-stage high-risk prostate cancer is challenging, with established measures such as overall survival and metastasis-free survival facing limitations related to feasibility and adequate reflection of patient relevance. Developing endpoints must cater to diverse perspectives across scientific, clinical, regulatory, and patient viewpoints. Endpoints such as pathological complete response, no evidence of disease, and prevention of prostate-specific antigen relapse may reflect patient benefit by accounting for diagnostic and treatment burdens.

Variation in content discussed by specialty in consultations for clinically localized prostate cancer.

INTRODUCTION: Multidisciplinary consultations improve decisional conflict and guideline-concordant treatment for men with prostate cancer (PC), but differences in the content discussed by specialty during consultations are unknown. METHODS: We audiorecorded and transcribed 50 treatment consultations for localized PC across a multidisciplinary sample of urologists, radiation oncologists, and medical oncologists. Conversation was coded for narrative content using an open coding approach, grouping similar topics into major content areas. The number of words devoted to each content area per consult was used as a proxy for time spent. Multivariable Poisson regression calculated incidence rate ratios (IRR) for content-specific word count across specialties after adjustment for tumor risk and patient demographics. RESULTS: Coders identified 8 narrative content areas: overview of PC; medical history; baseline risk; cancer prognosis; competing risks; treatment options; physician recommendations; and shared decision making (SDM). In multivariable models, specialties significantly differed in proportion of time spent on treatment options, SDM, competing risks, and cancer prognosis. Urologists spent 1.8-fold more time discussing cancer prognosis than medical oncologists (IRR1.80, 95%CI:1.14-2.83) and radiation oncologists (IRR1.84, 95%CI:1.10-3.07). Urologists (IRR11.38, 95%CI:6.62-19.56) and medical oncologists (IRR10.60, 95%CI:6.01-18.72) spent over 10-fold more time discussing competing risks than radiation oncologists. Medical oncologists (IRR2.60, 95%CI:1.65-4.10) and radiation oncologists (IRR1.77, 95%CI:1.06-2.95) spent 2.6- and 1.8-fold more time on SDM than urologists, respectively. CONCLUSIONS: Specialists focus on different content in PC consultations. Our results suggest that urologists should spend more time on SDM and radiation oncologists on competing risks. Our results also highlight the importance of medical oncologists in facilitating SDM.

Applications of wearable activity monitors for prostate cancer survivors: A systematic scoping review.

BACKGROUND: Wearable technology is used to monitor and motivate physical activity (PA) and provides continuous, objective PA and sleep data outside the clinical setting. We reviewed the literature to understand how wearables are integrated into prostate cancer (PC) investigations in order to identify current practices, gaps, and research opportunities. METHODS: We conducted a literature search for articles using wearables, among PC survivors published between 2012 and 2022. We extracted study details, interventions and outcomes, participant baseline characteristics, and device characteristics and grouped them by study type: randomized control trials (RCTs) and non-randomized studies. RESULTS: Of 354 articles screened, 44 met eligibility criteria (23 RCTs, and 21 non-randomized). 89% used wearables to monitor PA metrics, 11%, sleep metrics, and 6.8%, both. Most studies involved exercise (70% RCTs, 9% non-randomized studies) or lifestyle interventions (30% RCTs, 9% non-randomized studies). Intervention delivery methods included personalized computer-based (48%), in-person (e.g., trainer) (20%), and education web or print-based (20%). Interventions occurred at the participant's home (48%) or at a gym (20%). 57% of the studies evaluated the feasibility and acceptability of the wearable as an activity-measuring device or as part of a remotely delivered computer-based intervention. Studies used wearables to monitor adherence to PA interventions, motivate behavior change, to assess patient outcomes (e.g., patient function, quality of life, mood), or as data collection tools. CONCLUSIONS: Wearables are primarily being used to assess daily activity and monitor adherence to exercise interventions in clinical studies involving PC survivors. Findings suggest that they are feasible for use in this population. More research is needed to understand how to integrate wearables into routine clinical care, expand their use to predict clinical outcomes, or to deliver tailored interventions for PC survivors.

Emerging racial disparities among Medicare beneficiaries and Veterans with metastatic castration-sensitive prostate cancer.

BACKGROUND: Previous studies have shown that Black men receive worse prostate cancer care than White men. This has not been explored in metastatic castration-sensitive prostate cancer (mCSPC) in the current treatment era. METHODS: We evaluated treatment intensification (TI) and overall survival (OS) in Medicare (2015-2018) and Veterans Health Administration (VHA; 2015-2019) patients with mCSPC, classifying first-line mCSPC treatment as androgen deprivation therapy (ADT) + novel hormonal therapy; ADT + docetaxel; ADT + first-generation nonsteroidal antiandrogen; or ADT alone. RESULTS: We analyzed 2226 Black and 16,071 White Medicare, and 1020 Black and 2364 White VHA patients. TI was significantly lower for Black vs White Medicare patients overall (adjusted odds ratio [OR] 0.68; 95% confidence interval [CI] 0.58-0.81) and without Medicaid (adjusted OR 0.70; 95% CI 0.57-0.87). Medicaid patients had less TI irrespective of race. OS was worse for Black vs White Medicare patients overall (adjusted hazard ratio [HR] 1.20; 95% CI 1.09-1.31) and without Medicaid (adjusted HR 1.13; 95% CI 1.01-1.27). OS was worse in Medicaid vs without Medicaid, with no significant OS difference between races. TI was significantly lower for Black vs White VHA patients (adjusted OR 0.75; 95% CI 0.61-0.92), with no significant OS difference between races. CONCLUSIONS: Guideline-recommended TI was low for all patients with mCSPC, with less TI in Black patients in both Medicare and the VHA. Black race was associated with worse OS in Medicare but not the VHA. Medicaid patients had less TI and worse OS than those without Medicaid, suggesting poverty and race are associated with care and outcomes.

Addressing racial disparities in prostate cancer pathology prediction models: external validation and comparison of four models of pathological outcome prediction before radical prostatectomy in the multiethnic SEARCH cohort.

BACKGROUND: Certain widely used pathological outcome prediction models that were developed in tertiary centers tend to overpredict outcomes in the community setting; thus, the Michigan Urological-Surgery Improvement Collaborative (MUSIC) model was developed in general urology practice to address this issue. Additionally, the development of these models involved a relatively small proportion of Black men, potentially compromising the accuracy of predictions in this patient group. We tested the validity of the MUSIC and three widely used nomograms to compare their overall and race-stratified predictive performance. METHODS: We extracted data from 4139 (1138 Black) men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database of the Veterans Affairs health system. The predictive performance of the MUSIC model was compared to the Memorial-Sloan Kettering (MSK), Briganti-2012, and Partin-2017 models for predicting lymph-node invasion (LNI), extra-prostatic extension (EPE), and seminal vesicle invasion (SVI). RESULTS: The median PSA of Black men was higher than White men (7.8 vs. 6.8 ng/ml), although they were younger by a median of three years and presented at a lower-stage disease. MUSIC model showed comparable discriminatory capacity (AUC:77.0%) compared to MSK (79.2%), Partin-2017 (74.6%), and Briganti-2012 (76.3%), with better calibration for LNI. AUCs for EPE and SVI were 72.7% and 76.9%, respectively, all comparable to the MSK and Partin models. LNI AUCs for Black and White men were 69.6% and 79.6%, respectively, while EPE and SVI AUCs were comparable between races. EPE and LNI had worse calibration in Black men. Decision curve analysis showed MUSIC superiority over the MSK model in predicting LNI, especially among Black men. CONCLUSION: Although the discriminatory performance of all models was comparable for each outcome, the MUSIC model exhibited superior net benefit to the MSK model in predicting LNI outcomes among Black men in the SEARCH population.

Racial disparities in stage at bladder cancer diagnosis in the US Veterans Affairs healthcare system.

OBJECTIVE: To describe patient characteristics and pathological stage at bladder cancer (BCa) diagnosis in a diverse population within a national, equal-access healthcare system. METHODS: This retrospective cohort study identified 15 966 men diagnosed with BCa in the Veterans Affairs (VA) healthcare system from 2000 to 2020. The primary outcome was pathological stage at diagnosis, determined by index transurethral resection of bladder tumour. Logistic regression was used to assess the relationship between race and stage. Competing risk models tested the association between race and BCa-specific mortality with cumulative incidence estimates. RESULTS: Of 15 966 BCa patients, 12 868 (81%), 1726 (11%), 493 (3%) and 879 (6%) were White, Black, Hispanic and Other race, respectively. Black patients had significantly higher muscle-invasive bladder cancer (MIBC) rates than White patients (35% vs 32%; P = 0.009). In multivariable analysis, the odds of presenting with MIBC did not differ significantly between Black and White patients (odds ratio [OR] 1.10, 95% confidence interval [CI] 0.98-1.22) or between Hispanic patients (OR 0.82, 95% CI 0.67-1.01) and White patients. Compared to White patients, Black patients had a similar risk of BCa-specific mortality (hazard ratio [HR] 0.89, 95% CI 0.75-1.06), whereas Hispanic patients had a lower risk (HR 0.56, 95% CI 0.38-0.82). CONCLUSIONS: Black patients presented with the highest rates of de novo MIBC. However, in a large, equal-access healthcare system, this did not result in a difference in BCa-specific mortality. In contrast, Hispanic patients had lower risks of MIBC and BCa-specific mortality.

Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies.

BACKGROUND: Evidence of an association between dietary fiber intake and risk of advanced and aggressive forms of prostate cancer (PC) and PC mortality is limited. OBJECTIVE: The aim of this study was to examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC. DESIGN: The study design was a pooled analysis of the primary data from 15 cohorts in 3 continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study. PARTICIPANTS/SETTING: There were 842 149 men followed for up to 9 to 22 years between 1985 and 2009 across studies. MAIN OUTCOME MEASURES: The primary outcome measures were advanced (stage T4, N1, or M1 or PC mortality), advanced restricted (excluded men with missing stage and those with localized PC who died of PC), and high-grade PC (Gleason score ≥8 or poorly differentiated/undifferentiated) and PC mortality. STATISTICAL ANALYSIS PERFORMED: Study-specific multivariable hazard ratios (MVHR) were calculated using Cox proportional hazards regression and pooled using random effects models. RESULTS: Intake of dietary fiber overall, from fruits, and from vegetables was not associated with risk of advanced (n = 4863), advanced restricted (n = 2978), or high-grade PC (n = 9673) or PC mortality (n = 3097). Dietary fiber intake from grains was inversely associated with advanced PC (comparing the highest vs lowest quintile, MVHR 0.84; 95% CI 0.76-0.93), advanced restricted PC (MVHR 0.85; 95% CI 0.74-0.97), and PC mortality (MVHR 0.78; 95% CI 0.68-0.89); statistically significant trends were noted for each of these associations (P ≤ .03), and a null association was observed for high-grade PC for the same comparison (MVHR 1.00; 95% CI 0.93-1.07). The comparable results were 1.06 (95% CI 1.01-1.10; P value, test for trend = .002) for localized PC (n = 35,199) and 1.05 (95% CI 0.99-1.11; P value, test for trend = .04) for low/intermediate grade PC (n = 34 366). CONCLUSIONS: Weak nonsignificant associations were observed between total dietary fiber intake and risk of advanced forms of PC, high-grade PC, and PC mortality. High dietary fiber intake from grains was associated with a modestly lower risk of advanced forms of PC and PC mortality.

Do Hispanic Puerto Rican men have worse outcomes after radical prostatectomy? Results from SEARCH.

BACKGROUND: We previously reported that outcomes after radical prostatectomy (RP) were similar among non-Hispanic Black, non-Hispanic White, and Hispanic White Veterans Affairs (VA) patients. However, prostate cancer (PC) mortality in Puerto Rican Hispanics (PRH) may be higher than in other Hispanic groups. Data focused on PRH patients is sparse; thus, we tested the association between PR ethnicity and outcomes after RP. METHODS: Analysis included men in SEARCH cohort who underwent RP (1988-2020, n = 8311). PRH patients (n = 642) were treated at the PR VA, and outcomes were compared to patients treated in the Continental US regardless of race. Logistic regression was used to test the associations between PRH and PC aggressiveness, adjusting for demographic and clinicopathological features. Multivariable Cox models were used to investigate PRH versus Continental differences in biochemical recurrence (BCR), metastases, castration-resistant PC (CRPC), and PC-specific mortality (PCSM). RESULTS: Compared to Continental patients, PRH patients had lower adjusted odds of pathological grade group ≥2 (p < 0.001), lymph node metastasis (p < 0.001), and positive margins (p < 0.001). In contrast, PRH patients had higher odds of extracapsular extension (p < 0.001). In Cox models, PRH patients had a higher risk for BCR (HR = 1.27, p < 0.001), metastases (HR = 1.49, p = 0.014), CRPC (HR = 1.80, p = 0.001), and PCSM (HR = 1.74, p = 0.011). Further adjustment for extracapsular extension and other pathological variables strengthened these findings. CONCLUSIONS: In an equal access setting, PRH RP patients generally had better pathological features, but despite this, they had significantly worse post-treatment outcomes than men from the Continental US, regardless of race. The reasons for the poorer prognosis among PRH men require further research.

A practical guide for assessing and managing cardiovascular risk during androgen-deprivation therapy in patients with prostate cancer.

Prostate cancer is the most common malignancy among men worldwide, and androgen-deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk. Because, for most patients with prostate cancer, death is predominantly from noncancer-related causes, cardiovascular disease and its risk factors should be optimized during cancer treatment. This review provides an overview of the landscape of ADT treatment and serves as a guide for appropriate cardiovascular screening and risk-mitigation strategies. The authors emphasize the importance of shared communication between the multidisciplinary cancer team and primary care to improve baseline cardiovascular screening and treatment of modifiable risk factors within this higher risk population.

Contemporary risk of biochemical recurrence after radical prostatectomy in the active surveillance era.

OBJECTIVES: To assess whether contemporary risks of biochemical recurrence (BCR) after radical prostatectomy (RP) in the AS era differ from historical estimates due to changes in tumor risk case mix and improvements in risk stratification. MATERIALS AND METHODS: We sampled 6,682 men who underwent RP for clinically localized disease between 2000 and 2017 from the VA SEARCH database. Kaplan Meier analysis was used to calculate incidence of BCR before and after 2010 overall and within tumor risk subgroups. Multivariable Cox proportional hazard regression analysis including an interaction term between era and tumor risk was used to compare risk of BCR before and after 2010 overall and across tumor risk subgroups. RESULTS: About 3,492 (52%) and 3,190 (48%) men underwent RP before and after 2010, respectively. In a limited multivariable model excluding tumor risk, overall BCR risk was higher post-2010 vs. pre-2010 (HR: 1.15, 95%CI: 1.05-1.25; 40% vs 36% at 8 years post-RP). However, this effect was eliminated after correcting for tumor risk (HR: 0.95, 95%CI: 0.87-1.04), suggesting that differences in tumor risk between eras mediated the change. Yet, within tumor-risk subgroups, BCR risk was significantly lower for favorable intermediate-risk (HR: 0.76, 95%CI:0.60-0.96) and unfavorable intermediate-risk PC (HR: 0.78, 95%CI: 0.67-0.90), but significantly higher for high-risk PC (HR: 1.22, 95%CI: 1.07-1.38) in the post-2010 era. 8-year risks of BCR in the post-2010 era were 21% (95%CI: 16%-25%), 25% (95%CI: 20%-30%), 41% (95%CI: 37%-46%), and 60% (95%CI: 56%-64%) for low-, FIR-, UIR-, and high-risk disease, respectively. Limitations include limited long-term follow-up in the post-2010 subgroup. CONCLUSIONS: Overall BCR risk has increased in the AS era, driven by a higher risk case mix and increased BCR risk among high-risk patients. Physicians should quote contemporary estimates of BCR when counseling patients.

Drug-drug interaction potential among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with novel androgen receptor inhibitors.

BACKGROUND: Nonmetastatic castration-resistant prostate cancer (nmCRPC) patients are often older and use concurrent medications that increase the potential for drug-drug interactions (pDDIs). This study assessed pDDI prevalence in real-world nmCRPC patients treated with apalutamide, darolutamide, or enzalutamide. RESEARCH DESIGN AND METHODS: Castrated prostate cancer patients without metastases prior to androgen receptor inhibitor initiation were identified retrospectively via Optum Clinformatics Data Mart claims data (8/2019-3/2021). The top 100 concomitant medications were assessed for pDDIs. RESULTS: Among 1,515 patients (mean age: 77 ± 8 years; mean Charlson Comorbidity Index: 3 ± 3), 340 initiated apalutamide, 112 darolutamide, and 1,063 enzalutamide. Common concomitant medication classes were cardiovascular (80%) and central nervous system (52%). Two-thirds of the patients received ≥5 concomitant medications; 30 (30/100 medications) pDDIs were identified for apalutamide and enzalutamide each and 2 (2/100 medications) for darolutamide. Most pDDIs had risk ratings of C or D, but four for apalutamide were rated X. Approximately 58% of the patients on apalutamide, 5% on darolutamide, and 54% on enzalutamide had ≥1 identified pDDI. CONCLUSIONS: Results showed a higher frequency of pDDIs in patients receiving apalutamide and enzalutamide vs darolutamide. The impact of these could not be determined retrospectively. DDI risk should be carefully evaluated when discussing optimal therapy for patients with nmCRPC.

Real-world overall survival with abiraterone acetate versus enzalutamide in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

BACKGROUND: There are no large head-to-head phase 3 clinical trials comparing overall survival (OS) for abiraterone and enzalutamide. This study used Medicare claims data to compare OS in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) who initiated abiraterone or enzalutamide. METHODS: This retrospective analysis of the Medicare database (2009-2020) included adult men with ≥1 claim for prostate cancer, metastatic diagnosis, and no prior chemotherapy or novel hormone therapy who initiated first-line (1L) abiraterone or enzalutamide in the index period (September 10, 2014 to May 31, 2017). Cox proportional-hazards models with inverse probability treatment-weighting (IPTW) were used to compare OS between abiraterone- and enzalutamide-treated patients, adjusting for baseline characteristics. Subgroup analyses by baseline characteristics were also conducted. RESULTS: Overall, 5506 patients who received 1L abiraterone (n = 2911) or enzalutamide (n = 2595) were included. Median follow-up was comparable in both cohorts (abiraterone, 19.1 months; enzalutamide, 20.3 months). IPTW-adjusted median OS (95% CI) was 20.6 months (19.7‒21.4) for abiraterone and 22.5 months (21.2‒23.8) for enzalutamide, with an IPTW-adjusted hazard ratio (95% CI) of 1.10 (1.04-1.16). Median OS was significantly shorter for abiraterone versus enzalutamide in patients ≥75 years old; White patients; patients with baseline diabetes, cardiovascular disease, both diabetes and cardiovascular disease, and renal disease; and across all socioeconomic strata. CONCLUSIONS: In the Medicare chemotherapy-naïve mCRPC population, 1L abiraterone was associated with worse OS versus enzalutamide in the overall population and among subgroups with older age and comorbidities, supporting findings from previous real-world studies and demonstrating a disparity in outcomes.

Filamin A Is a Prognostic Serum Biomarker for Differentiating Benign Prostatic Hyperplasia from Prostate Cancer in Caucasian and African American Men.

Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, PSA's screening utility is diminished, resulting in many unnecessary biopsies. To address this issue, we previously identified a cleaved fragment of Filamin A (FLNA) protein (as measured with IP-MRM mass spectrometry assessment as a prognostic biomarker for stratifying BPH from prostate cancer and subsequently evaluated its expanded utility in Caucasian (CA) and African American (AA) men. All men had a negative digital rectal examination (DRE) and PSA between 4 and 10 ng/mL and underwent prostate biopsy. In AA men, FLNA serum levels exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.71 AUC and 12.2 OR in 48 men with BPH and 60 men with PCa) and outperformed PSA (0.50 AUC, 2.2 OR). In CA men, FLNA serum levels also exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.74 AUC and 19.4 OR in 191 men with BPH and 109 men with PCa) and outperformed PSA (0.46 AUC, 0.32 OR). Herein, we established FLNA alone as a serum biomarker for stratifying men with BPH vs. those with high Gleason (7-10) prostate cancers compared to the current diagnostic paradigm of using PSA. This approach demonstrates clinical actionability of FLNA alone without the requirement of prostate volume measurement as a test with utility in AA and CA men and represents a significant opportunity to decrease the number of unnecessary biopsies in aggressive prostate cancer diagnoses.