Development and Validation of a Prostate Biopsy Risk Calculator in Black Men.

PURPOSE: We sought to develop and validate a prostate biopsy risk calculator for Black men and compare it with the Prostate Cancer Prevention Trial version 2.0, Prostate Biopsy Collaborative Group, and Kaiser Permanente Prostate Cancer Risk Calculators for the detection of Gleason Grade Group (GG) ≥ 2 prostate cancer (PCa). MATERIALS AND METHODS: We prospectively recruited 2 cohorts of men undergoing prostate biopsy from 5 facilities in Chicago. The first cohort was split into development (70%) and internal validation (30%) groups. The second was used for external validation. Iterative logistic regression was used to develop 3 models for predicting GG ≥ 2 PCa. Models were compared for discrimination using the C statistics, calibration curves, and net benefit curves. The frequency of unnecessary biopsies and missed PCas was compared at 10% and 30% risk thresholds. RESULTS: The 2 cohorts included 393 and 292 Black men, respectively. Our first model, Mistry-Sun 1, used serum PSA and prior negative biopsy. Mistry-Sun 2 added abnormal digital rectal exam (DRE) and an interaction term with abnormal DRE and PSA to Mistry-Sun 1. Mistry-Sun 3 added prostate volume, abnormal DRE, and age to Mistry-Sun 1. The C statistics were 0.74, 0.74, and 0.78, respectively, and were similar to or higher than established calculators. At the 10% and 30% risk thresholds our models had the fewest unnecessary biopsies and an appropriate proportion of missed GG ≥ 2 PCas. CONCLUSIONS: Tailoring a risk calculator to detect clinically significant PCa in Black men may improve biopsy decision-making and outcomes compared to tools developed in non-Black populations.

Cardiometabolic comorbidities in Hispanic/Latino cancer survivors: prevalence and impact on health-related quality of life and supportive care needs.

PURPOSE: The aim of this study was to characterize the prevalence of cardiometabolic comorbidities (i.e., diabetes, peripheral vascular disease, myocardial infarction, congestive heart failure, cerebrovascular disease) among Hispanic/Latino cancer survivors and examine the impact of cardiometabolic comorbidities on health-related quality of life (HRQoL), unmet supportive care needs, patient-provider communication self-efficacy, satisfaction with cancer care, and increases in healthy behaviors. METHODS: Hispanics/Latinos diagnosed with breast, prostate, or colorectal cancer (N = 288) were assessed within 15 months of primary treatment completion. RESULTS: One-quarter (24.7%) of survivors were diagnosed with diabetes and one-fifth (20.8%) were diagnosed with peripheral vascular disease. Survivors with at least one cardiometabolic comoribidity were older (t(278) = -.3.622, p < .001) and more likely to have a household income of less than $25,000 (X2 = 8.369, p = .004). When adjusting for sociodemographic and medical covariates, survivors with cardiometabolic comorbidities demonstrated worse overall HRQoL (B = -4.792, p = .050), emotional (B = -1.479, p = .018) and physical (B = -2.228, p = .005) wellbeing, a higher odds of unmet psychological (OR = 2.095, p = .027) and sexuality (OR = 2.898, p = .004) needs, and greater patient-provider communication self-efficacy (B = .179, p = .045). There were no differences in healthy behavior changes or satisfaction with cancer care. CONCLUSIONS: Cardiometabolic comorbidities may be highly prevalent among Hispanic/Latino cancer survivors and increase the risk of worse HRQoL and unmet supportive care needs. Targeted interventions are needed to optimize health among Hispanic/Latino cancer survivors with cardiometabolic comorbidities.

Impact of genomic testing on urologists' treatment preference in favorable risk prostate cancer: A randomized trial.

INTRODUCTION: The Oncotype Dx Genomic Prostate Score (GPS) is a 17-gene relative expression assay that predicts adverse pathology at prostatectomy. We conducted a novel randomized controlled trial to assess the impact of GPS on urologist's treatment preference for favorable risk prostate cancer (PCa): active surveillance versus active treatment (i.e., prostatectomy/radiation). This is a secondary endpoint from the ENACT trial which recruited from three Chicago hospitals from 2016 to 2019. METHODS: Ten urologists along with men with very low to favorable-intermediate risk PCa were included in the study. Participants were randomly assigned to standardized counseling with or without GPS assay. The main outcome was urologists' preference for active treatment at Visit 2 by study arm (GPS versus Control). Multivariable best-fit binary logistic regressions were constructed to identify factors independently associated with urologists' treatment preference. RESULTS: Two hundred men (70% Black) were randomly assigned to either the Control (96) or GPS arm (104). At Visit 2, urologists' preference for prostatectomy/radiation almost doubled in the GPS arm to 29.3% (29) compared to 14.1% (13) in the Control arm (p = 0.01). Randomization to the GPS arm, intermediate NCCN risk level, and lower patient health literacy were predictors for urologists' preference for active treatment. DISCUSSION: Limitations included sample size and number of urologists. In this study, we found that GPS testing reduced urologists' likelihood to prefer active surveillance. CONCLUSIONS: These findings demonstrate how obtaining prognostic biomarkers that predict negative outcomes before treatment decision-making might influence urologists' preference for recommending aggressive therapy in men eligible for active surveillance.

A latent class analysis of health behavior changes after cancer diagnosis among Hispanic/Latino cancer survivors.

PURPOSE: We aimed to identify subgroups of Hispanic/Latino (H/L) cancer survivors with distinct health behavior patterns and their associated sociodemographic, medical, and psychosocial characteristics. METHODS: Baseline data were used from a randomized clinical trial evaluating the efficacy of an enhanced patient navigation intervention in H/L cancer survivors. Participants (n = 278) completed the Lifestyle Behavior Scale and validated questionnaires on health-related quality of life (HRQOL), supportive care needs, distress, and satisfaction with cancer care. Latent class analysis was used to determine the latent classes and associated characteristics. RESULTS: Three latent classes emerged: class 1 (survivors who increased health behaviors [e.g., exercising and eating healthy] since diagnosis); class 2 (no changes in health behaviors since diagnosis); and class 3 (a "mixed class," with a higher or lower engagement across various health behaviors since diagnosis). Participants in class 1 were significantly more educated and less likely to be foreign born. Participants in class 2 were significantly older and more likely to have prostate cancer. H/L cancer survivors in class 3 had a significantly lower income, were less educated, and reported greater unmet supportive care needs, more distress, and poorer HRQOL. CONCLUSIONS: Survivors who report engaging in health behaviors less frequently since diagnosis may be experiencing psychosocial challenges and health disparities. IMPLICATIONS FOR CANCER SURVIVORS: Hispanic/Latino cancer survivors may benefit from screening for social determinants of health and mental health needs, prompt referral to supportive care services, community resources, and public services, and participating in culturally informed psychosocial interventions to address their unique needs.

Enzalutamide Monotherapy vs Active Surveillance in Patients With Low-risk or Intermediate-risk Localized Prostate Cancer: The ENACT Randomized Clinical Trial.

Importance: There are few published studies prospectively assessing pharmacological interventions that may delay prostate cancer progression in patients undergoing active surveillance (AS). Objective: To compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer. Design, Setting, and Participants: The ENACT study was a phase 2, open-label, randomized clinical trial conducted from June 2016 to August 2020 at 66 US and Canadian sites. Eligible patients were 18 years or older, had received a diagnosis of histologically proven low-risk or intermediate-risk localized prostate cancer within 6 months of screening, and were undergoing AS. Patients were monitored during 1 year of treatment and up to 2 years of follow-up. Data analysis was conducted in February 2021. Interventions: Randomized 1:1 to enzalutamide, 160 mg, monotherapy for 1 year or continued AS, as stratified by cancer risk and follow-up biopsy type. Main Outcomes and Measures: The primary end point was time to pathological or therapeutic prostate cancer progression (pathological, ≥1 increase in primary or secondary Gleason pattern or ≥15% increased cancer-positive cores; therapeutic, earliest occurrence of primary therapy for prostate cancer). Secondary end points included incidence of a negative biopsy result, percentage of cancer-positive cores, and incidence of a secondary rise in serum prostate-specific antigen (PSA) levels at 1 and 2 years, as well as time to PSA progression. Adverse events were monitored to assess safety. Results: A total of 114 patients were randomized to treatment with enzalutamide plus AS and 113 to AS alone; baseline characteristics were similar between treatment arms (mean [SD] age, 66.1 [7.8] years; 1 Asian individual [0.4%], 21 Black or African American individuals [9.3%], 1 Hispanic individual [0.4%], and 204 White individuals [89.9%]). Enzalutamide significantly reduced the risk of prostate cancer progression by 46% vs AS (hazard ratio, 0.54; 95% CI, 0.33-0.89; P = .02). Compared with AS, odds of a negative biopsy result were 3.5 times higher; there was a significant reduction in the percentage of cancer-positive cores and the odds of a secondary rise in serum PSA levels at 1 year with treatment with enzalutamide; no significant difference was observed at 2 years. Treatment with enzalutamide also significantly delayed PSA progression by 6 months vs AS (hazard ratio, 0.71; 95% CI, 0.53-0.97; P = .03). The most commonly reported adverse events during enzalutamide treatment were fatigue (62 [55.4%]) and gynecomastia (41 [36.6%]). Three patients in the enzalutamide arm died; none were receiving the study drug at the time of death. No deaths were considered treatment-related. Conclusions and Relevance: The results of this randomized clinical trial suggest that enzalutamide monotherapy was well-tolerated and demonstrated a significant treatment response in patients with low-risk or intermediate-risk localized prostate cancer. Enzalutamide may provide an alternative treatment option for patients undergoing AS. Trial Registration: ClinicalTrials.gov Identifier: NCT02799745.

Impact of a Genomic Test on Treatment Decision in a Predominantly African American Population With Favorable-Risk Prostate Cancer: A Randomized Trial.

PURPOSE: The Genomic Prostate Score (GPS), performed on biopsy tissue, predicts adverse outcome in prostate cancer (PCa) and has shown promise for improving patient selection for active surveillance (AS). However, its impact on treatment choice in high-risk populations of African Americans is largely unknown and, in general, the effect of the GPS on this difficult decision has not been evaluated in randomized trials. METHODS: Two hundred men with National Comprehensive Cancer Network very low to low-intermediate PCa from three Chicago hospitals (70% Black, 16% college graduates) were randomly assigned at diagnosis to standard counseling with or without a 12-gene GPS assay. The primary end point was treatment choice at a second postdiagnosis visit. The proportion of patients choosing AS was compared, and multivariable modeling was used to estimate the effects of various factors on AS acceptance. RESULTS: AS acceptance was high overall, although marginally lower in the intervention group (77% v 88%; P = .067), and lower still when men with inadequate specimens were excluded (P = .029). Men with lower health literacy who received a GPS were seven-fold less likely to choose AS compared with controls, whereas no difference was seen in men with higher health literacy (Pinteraction = .022). Among men with low-intermediate risk, 69% had GPS values consistent with unfavorable intermediate or high-risk cancer. AS choice was also independently associated with a family history of PCa and having health insurance. CONCLUSION: In contrast to other studies, the net effect of the GPS was to move patients away from AS, primarily among men with low health literacy. These findings have implications for our understanding of how prognostic molecular assays that generate probabilities of poor outcome can affect treatment decisions in diverse clinical populations.

Genetic loci associated with skin pigmentation in African Americans and their effects on vitamin D deficiency.

A recent genome-wide association study (GWAS) in African descent populations identified novel loci associated with skin pigmentation. However, how genomic variations affect skin pigmentation and how these skin pigmentation gene variants affect serum 25(OH) vitamin D variation has not been explored in African Americans (AAs). In order to further understand genetic factors that affect human skin pigmentation and serum 25(OH)D variation, we performed a GWAS for skin pigmentation with 395 AAs and a replication study with 681 AAs. Then, we tested if the identified variants are associated with serum 25(OH) D concentrations in a subset of AAs (n = 591). Skin pigmentation, Melanin Index (M-Index), was measured using a narrow-band reflectometer. Multiple regression analysis was performed to identify variants associated with M-Index and to assess their role in serum 25(OH)D variation adjusting for population stratification and relevant confounding variables. A variant near the SLC24A5 gene (rs2675345) showed the strongest signal of association with M-Index (P = 4.0 x 10-30 in the pooled dataset). Variants in SLC24A5, SLC45A2 and OCA2 together account for a large proportion of skin pigmentation variance (11%). The effects of these variants on M-Index was modified by sex (P for interaction = 0.009). However, West African Ancestry (WAA) also accounts for a large proportion of M-Index variance (23%). M-Index also varies among AAs with high WAA and high Genetic Score calculated from top variants associated with M-Index, suggesting that other unknown genomic factors related to WAA are likely contributing to skin pigmentation variation. M-Index was not associated with serum 25(OH)D concentrations, but the Genetic Score was significantly associated with vitamin D deficiency (serum 25(OH)D levels less than 12 ng/mL) (OR, 1.30; 95% CI, 1.04-1.64). The findings support the hypothesis suggesting that skin pigmentation evolved responding to increased demand for subcutaneous vitamin D synthesis in high latitude environments.

Performance of prostate health index and PSA density in a diverse biopsy-naïve cohort with mpMRI for detecting significant prostate cancer.

Objective: To compare Prostate Health Index (PHI) and prostate-specific antigen (PSA) density as secondary tests after multiparametric magnetic resonance imaging (mpMRI) in improving the detection accuracy of Gleason grade group (GG) 2-5 prostate cancer (PCa) and in decreasing unnecessary biopsies in a multiethnic biopsy-naïve population. Methods: From February 2017 to February 2020, we recruited consecutive biopsy-naïve men in participating urology clinics for elevated PSA levels. They all had a PHI score, mpMRI, and prostate biopsy. Experienced genitourinary radiologists read all mpMRI studies based on PIRADS version 2.0. Logistic regression models were used to generate receiver operating characteristic curves. Models were tested for effect modification between Race (Black vs White) and both PHI and PSA density, and Race and PIRADS to determine if race impacted their prediction accuracy. Sensitivity, specificity, and predictive values of PHI and PSA density thresholds were calculated by PIRADS scores. The primary outcome was GG2-5 PCa, that is, Gleason score ≥3 + 4. Results: The study included 143 men, of which 65 (45.5%) were self-reported Black. Median age was 62.0 years and 55 men (38.4%) had GG2-5 PCa. Overall, 18.1% had PIRADS 1-2, 32.9% had PIRADS 3, and 49.0% had PIRADS 4-5. For the binary logistic regressions, the interactions between PIRADS and Race (P = .08), Log (PHI) and Race (P = .17), and Log (PSA density) and Race (P = .42) were not statistically significant. Within PIRADS 3 lesions, a PHI ≥49 prevented unnecessary biopsies in 55% of men and missed no GG2-5 PCa, yielding a negative predictive value of 100%. There was no reliable PHI or PSA density threshold to avoid PCa biopsies in PIRADS 1-2 or 4-5. Conclusions: PHI and PSA density can be used after mpMRI to improve the detection of GG2-5 PCa in a biopsy-naïve cohort. PHI may be superior to PSA density in PIRADS 3 lesions by avoiding 55% of unnecessary biopsies. Using both PHI and PSA density in series may further increase specificity and lead to fewer unnecessary biopsies, but further larger studies are warranted to determine the optimal threshold of each biomarker.

Performance of Prostate Health Index in Biopsy Naïve Black Men.

PURPOSE: The Prostate Health Index is validated for prostate cancer detection but has not been well validated for Gleason grade group 2-5 prostate cancer detection in Black men. We hypothesize that the Prostate Health Index has greater accuracy than prostate specific antigen for detection of Gleason grade group 2-5 prostate cancer. We estimated probability of overall and Gleason grade group 2-5 prostate cancer across previously established Prostate Health Index ranges and identified Prostate Health Index cutoffs that maximize specificity for Gleason grade group 2-5 prostate cancer with sensitivity >90%. MATERIALS AND METHODS: We recruited a "cancer-free" Black control cohort (135 patients) and a cohort of biopsy naïve Black men (158) biopsied for elevated prostate specific antigen. Descriptive statistics compared the prostate cancer cases and controls and the frequency of Gleason grade group 2-5 prostate cancer across Prostate Health Index scores. Receiver operating characteristics compared the discrimination of prostate specific antigen, Prostate Health Index and other prostate specific antigen related biomarkers. Sensitivity and specificity for Gleason grade group 2-5 prostate cancer detection were assessed at prostate specific antigen and Prostate Health Index thresholds alone and in series. RESULTS: Of biopsied subjects 32.9% had Gleason grade group 2-5 prostate cancer. In Blacks with prostate specific antigen from 4.0-10.0 ng/ml, Prostate Health Index and prostate specific antigen had similar discrimination for Gleason grade group 2-5 prostate cancer (0.63 vs 0.57, p=0.27). In Blacks with prostate specific antigen ≤10.0, a threshold of prostate specific antigen ≥4.0 had 90.4% sensitivity for Gleason grade group 2-5 prostate cancer; a threshold of prostate specific antigen ≥4.0 with Prostate Health Index ≥35.0 in series avoided unnecessary biopsy in 33.0% of men but missed 17.3% of Gleason grade group 2-5 prostate cancer. Prostate specific antigen ≥4.0 with Prostate Health Index ≥28.0 in series spared biopsy in 17.9%, while maintaining 90.4% sensitivity of Gleason grade group 2-5 prostate cancer. CONCLUSIONS: The Prostate Health Index has moderate accuracy in detecting Gleason grade group 2-5 prostate cancer in Blacks, but Prostate Health Index ≥28.0 can be safely used to avoid some unnecessary biopsies in Blacks.

Prostate cancer presentation, treatment selection, and outcomes among men with HIV/AIDS: A clinical stage, race, and age-matched contemporary analysis.

PURPOSE: To compare the clinical presentation, treatment receipt, and oncologic outcomes between human immunodeficiency virus-seropositive (HIV+) and seronegative (HIV-) men with prostate cancer (CaP) matched by age, clinical stage, and race. MATERIALS AND METHODS: A retrospective review of 3,135 men treated for CaP from 2000 to 2016 was performed. HIV+ patients (N = 46) were matched 1:2 to 3 to HIV- men (N = 137) by age, race, and clinical stage. Clinicopathologic features and primary treatment received were compared between cohorts. Associations between HIV status and progression-free, cancer-specific, and overall survival were compared by HIV status using the Kaplan-Meier method and Cox proportional hazards analysis. RESULTS: After matching, men with and without HIV were similar with respect initial prostate-specific antigen, Gleason Sum, and Eastern Cooperative Oncology Group (ECOG) performance status. Among HIV+ men, 67.4% had a history of acquired immune deficiency syndrome, and 91.3% were on highly active antiretroviral therapy at CaP diagnosis. Among men with localized disease, HIV+ men were more likely to receive radiation (59.5% vs. 44.8%) or no therapy (13.5% vs. 4.3%) and less likely to receive surgery (16.2% vs. 30.2%), or to initiate active surveillance (10.8% vs. 16.4%; P = 0.04 overall). There were no differences in rates of clinical progression, development of castration resistance, or CaP death by HIV status. However, HIV+ status was associated with inferior overall survival (hazard ratio 2.89, P = 0.04). CONCLUSIONS: While most HIV+ patients had a history of acquired immune deficiency syndrome; HIV was well controlled in the majority of patients at the time of CaP diagnosis. While oncologic outcomes were similar between HIV+ and HIV- men, significant differences in treatment selection were observed. Further research is necessary to understand differences in treatment election by HIV status and to define optimal CaP treatment selection in men with HIV.

Predictive Risk Factors for Continued Smoking after the Diagnosis of a Genitourinary Malignancy.

OBJECTIVE: To determine risk factors for continued smoking following a diagnosis of a genitourinary (GU) malignancy. Smoking is a well established risk factor in the development of cancers involving the GU tract. Unfortunately, a large percentage of patients continue to smoke or relapse after cancer diagnosis; by doing so, there is an increased risk of recurrence, poor survival rates, treatment complications, secondary primary cancers, and other chronic smoking related illnesses. MATERIALS AND METHODS: Two hundred and five patients who presented to a Urologic Oncology clinic at a single tertiary treatment center were given smoking cessation counseling and pharmacotherapy, as well as a questionnaire which was used to identify smoking status, demographics, and behavioral/psychosocial characteristics. Patients were followed for a minimum of 1 year with a median length of follow up for 13 months. RESULTS: 91% of patients enrolled in the study continued smoking at survey completion. After accounting for age, ethnicity, education and cigarettes consumed/day, 5 variables were independently associated with an increased risk of continued smoking: smoking 20 or more cigarettes per day, less than 2 prior quit attempts, anxiety and/or depression, fear of cancer recurrence, and home secondhand smoke exposure. CONCLUSION: The role of the urologist is imperative for encouraging smoking cessation. While every patient should receive adequate counseling regarding smoking at the time of a GU malignancy diagnosis, identifying patients with the risk factors noted in this study and augmenting smoking cessation efforts may result in stronger efforts to quit and prevention of long-term complications.

Urotrauma Guideline 2020: AUA Guideline.

PURPOSE: The authors of this guideline reviewed the urologic trauma literature to guide clinicians in the appropriate methods of evaluation and management of genitourinary injuries. MATERIALS AND METHODS: The Panel amended the Guideline in 2020 to reflect additional literature published through February 2020. When sufficient evidence existed, the Panel assigned the body of evidence a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, the Panel provided additional information as Clinical Principles and Expert Opinions (See table 1[Table: see text]). RESULTS: The Panel updated a total of six existing statements on renal, ureteral, bladder, urethra, and genital trauma. Additionally, four new statements were added based on literature released since the 2017 amendment. Statement 5b was added based on new evidence for treatment of hemodynamically unstable patients with renal trauma. Statement 20b was added based on new literature for percutaneous or open suprapubic tube placement following pelvic fracture urethral injury. Statements 30a and 30b were also added to provide guidance on ultrasonography for blunt scrotal injuries suggestive of testicular rupture and for performing surgical exploration with repair or orchiectomy for penetrating scrotal injuries respectively. CONCLUSIONS: These evidence-based updates to the AUA Guidelines further inform the treatment of urotrauma.

Low diagnostic sensitivity of cystoscopy and cystography of surgically confirmed vesicoenteric fistulae.

PURPOSE: The objective of this study was to assess the accuracy of cystoscopy and cystography, as compared to other diagnostic studies, in identifying vesicoenteric fistulae (VEF) in a contemporary series of patients with surgically confirmed VEF. METHODS: With institutional review board approval, we performed a single-center retrospective review of surgically confirmed VEF between 2002 and 2018. Demographic data, comorbidities, symptoms, and diagnostic evaluation were reviewed. The sensitivity, specificity, and accuracy of cystoscopy in diagnosis of VEF were compared to cross-sectional imaging. RESULTS: The study cohort consisted of 51 patients with surgically confirmed VEF secondary to diverticular disease. Diagnostic evaluation included cross-sectional imaging with CT (94%), colonoscopy (82%), cystoscopy (75%), cystography (53%), and barium enema (26%). Cystoscopic evaluation definitively demonstrated evidence of VEF in 34% of patients, while 55% of patients had nonspecific urothelial changes on cystoscopy without definitively demonstrating VEF. Comparatively, the sensitivity of VEF was 25% for cystography and 84% for CT. CONCLUSIONS: In clinical practice, the diagnostic work-up of VEF is variable. In the modern era of managed care, inclusion of cystoscopy and cystography in the evaluation of VEF does not contribute a substantial additive benefit over standard cross-sectional imaging. Cystoscopy and cystography could potentially be eliminated from the diagnostic evaluation of VEF, in the absence of a concern for malignancy, in an effort to minimize unnecessary invasive testing as well as health care expenditures.

Metastatic Thyroid Cancer Presenting as Renal Cortical Mass.

The authors present a rare case of primary diagnosis of metastatic, differentiated thyroid cancer presenting as a solitary, large renal mass. Renal cortical masses which represent metastatic primary malignancies are often small, multifocal, and in the setting of active malignancy. Surgical excision of this patient's renal mass demonstrated the unexpected diagnosis and subsequent endocrine surgical intervention.

Cutaneous metastasis of bladder urothelial carcinoma.

Cutaneous metastases of genitourinary malignancies are an extremely rare phenomenon. Few cases of skin metastasis from urothelial carcinoma of the bladder have been reported. We report a case of 71-year-old female with primary bladder transitional cell carcinoma who presented with the initial presentation of cutaneous skin lesions that covered the entire lower abdominal wall.