A regionally tailored epidemiological forecast and monitoring program to guide a healthcare system in the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, analytics and predictive models built on regional data provided timely, accurate monitoring of epidemiological behavior, informing critical planning and decision-making for health system leaders. At Atrium Health, a large, integrated healthcare system in the southeastern United States, a team of statisticians and physicians created a comprehensive forecast and monitoring program that leveraged an array of statistical methods. METHODS: The program utilized the following methodological approaches: (i) exploratory graphics, including time plots of epidemiological metrics with smoothers; (ii) infection prevalence forecasting using a Bayesian epidemiological model with time-varying infection rate; (iii) doubling and halving times computed using changepoints in local linear trend; (iv) death monitoring using combination forecasting with an ensemble of models; (v) effective reproduction number estimation with a Bayesian approach; (vi) COVID-19 patients hospital census monitored via time series models; and (vii) quantified forecast performance. RESULTS: A consolidated forecast and monitoring report was produced weekly and proved to be an effective, vital source of information and guidance as the healthcare system navigated the inherent uncertainty of the pandemic. Forecasts provided accurate and precise information that informed critical decisions on resource planning, bed capacity and staffing management, and infection prevention strategies. CONCLUSIONS: In this paper, we have presented the framework used in our epidemiological forecast and monitoring program at Atrium Health, as well as provided recommendations for implementation by other healthcare systems and institutions to facilitate use in future pandemics.

Is Active Surveillance Too Active?

PURPOSE OF REVIEW: Many prostate cancer active surveillance protocols mandate serial monitoring at defined intervals, including but certainly not limited to serum PSA (often every 6 months), clinic visits, prostate multiparametric MRI, and repeat prostate biopsies. The purpose of this article is to evaluate whether current protocols result in excessive testing of patients on active surveillance. RECENT FINDINGS: Multiple studies have been published in the past several years evaluating the utility of multiparametric MRI, serum biomarkers, and serial prostate biopsy for men on active surveillance. While MRI and serum biomarkers have promise with risk stratification, no studies have demonstrated that periodic prostate biopsy can be safely omitted in active surveillance. Active surveillance for prostate cancer is too active for some men with seemingly low-risk cancer. The use of multiple prostate MRIs or additional biomarkers do not always add to the prediction of higher-grade disease on surveillance biopsy.

Prognostic value of galectin-1 and galectin-3 expression in localized urothelial bladder cancer.

Background: Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are carbohydrate binding proteins with a wide range of biological activity, including regulation of cellular adhesion, proliferation, and apoptosis in solid tumors. Prior small studies have reported that Gal-3 expression is associated with progression of disease in urothelial carcinoma (UC), from non-muscle invasive UC progression to muscle invasive UC. We assessed Gal-1 and Gal-3 protein expression H-score utilizing a tissue microarray (TMA) created from 301 cystectomy specimens. Methods: Immunohistochemistry for Gal-1 and Gal-3 was performed on TMA generated from tumor blocks from chemotherapy naïve cystectomy specimens. The variable of interest, H-score, was defined as the product of the percentage of cells staining positive (0-100) and intensity score (0-3) scored by a single pathologist. Survival end points were analyzed using Kaplan-Meier and Cox Proportional Hazards methods. Clinical data including Charlson Comorbidity Index (CCI), pathologic tumor (T) stage, tumor size, node stage, and surgical margins, were included in multivariable analysis. Results: We found that Gal-1 and Gal-3 expression correlated with intratumoral T stage (median Gal-1 H-score was 0 across non-invasive tissue types and 200 in invasive, P<0.01 and median Gal-3 score was 270 across non-invasive tissue types and 70 in invasive, P<0.01). However, the highest intratumoral H-score per cystectomy core did not independently predict for recurrence-free survival (RFS) (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.65) or OS (Gal-1: HR =1.02, P=0.44, Gal-3: HR =1.01, P=0.72) in this cohort. Significant intratumoral heterogeneity was present for both Gal-1 and Gal-3, with an average difference between the highest and lowest H score was 95 for Gal-1 and 109 for Gal-3 for cystectomy specimens with more than one biopsy. Conclusions: Gal-1 and Gal-3 H-score per bladder did not independently predict for RFS or OS. Intra-tumoral Gal-1/Gal-3 heterogeneity complicates the use of Gal-1 and Gal-3 expression as a prognostic biomarker. Future studies should consider the evaluation of serum and urinary galectins as an approach to mitigate tumor heterogeneity.

Systematic review of reported association studies of monogenic genes and bladder cancer risk and confirmation analysis in a large population cohort.

Objectives: To evaluate which of previously reported monogenic genes are associated with increased bladder cancer risk, we reviewed published papers on associations of genes and bladder cancer risk and performed a confirmation study of these genes in a large population-based cohort. Subjects and methods: A systematic review of published papers prior to June 2022 was performed first to identify all genes where germline mutations were associated with bladder cancer risk. The associations of these candidate genes with bladder cancer risk were then tested among 1695 bladder cancer cases and 186 271 controls in the UK Biobank (UKB). The robust SKAT-O, a gene-based analysis that properly controls for type I error rates due to unbalanced case-control ratio, was used for association tests adjusting for age at recruitment, gender, smoking status, and genetic background. Results: The systematic review identified nine genes that were significantly associated with bladder cancer risk in at least one study (p < 0.05), including MUTYH, MSH2, MSH6, MLH1, ATM, BRCA2, ERCC5, TGFB1 and CHEK2. When pathogenic/likely pathogenic mutations were aggregated within each gene, the association was confirmed for three genes in the UKB at p < 0.0056 (Bonferroni correction for nine tests), including CHEK2, ATM and BRCA2, all also known to be associated with hereditary breast cancer. Suggestive evidence of association was found for two other genes, including MLH1 (p = 0.006) and MSH2 (p = 0.007), both known to be associated with Lynch syndrome. Among these five genes, the bladder cancer risks range from 1.60 (ATM) to 4.88 (MLH1), and mutation carrier rates in cases range from 0.06% (MSH2) to 2.01% (CHEK2). Conclusion: This study provides statistical evidence for association of previously reported genes and bladder cancer risk and has clinical utility for risk assessment and genetic counselling.

Moving Prostate Cancer Polygenic Risk Scores from Research Towards Clinical Practice.

Recent advances in our understanding of genetic factors that contribute to prostate cancer (PCa) susceptibility have the potential to improve disease screening, diagnosis, and treatment. Genetic risk scores in particular can more accurately inform patients of their risk of being diagnosed with PCa, which may help in decisions on whether to undergo prostate-specific antigen screening or prostate biopsy. Genetic information may also be useful in helping patients understand the etiology of their PCa and whether their family members should undergo more intensive screening. PATIENT SUMMARY: This mini review discusses recent advances in our understanding of how genetic factors influence a man's risk of developing prostate cancer. This information has the potential to improve screening, diagnosis, and patient counseling following a diagnosis of prostate cancer.

Characterization of prefusion-F-specific antibodies elicited by natural infection with human metapneumovirus.

Human metapneumovirus (hMPV) is a major cause of acute respiratory infections in infants and older adults, for which no vaccines or therapeutics are available. The viral fusion (F) glycoprotein is required for entry and is the primary target of neutralizing antibodies; however, little is known about the humoral immune response generated from natural infection. Here, using prefusion-stabilized F proteins to interrogate memory B cells from two older adults, we obtain over 700 paired non-IgM antibody sequences representing 563 clonotypes, indicative of a highly polyclonal response. Characterization of 136 monoclonal antibodies reveals broad recognition of the protein surface, with potently neutralizing antibodies targeting each antigenic site. Cryo-EM studies further reveal two non-canonical sites and the molecular basis for recognition of the apex of hMPV F by two prefusion-specific neutralizing antibodies. Collectively, these results provide insight into the humoral response to hMPV infection in older adults and will help guide vaccine development.

Racial and Socioeconomic Disparities in MRI-Fusion Biopsy Utilization to Assess for Prostate Cancer.

OBJECTIVE: To evaluate whether racial disparities in MRI-Bx usage persisted after correction for socioeconomic, demographic, and clinical factors. METHODS: This is a retrospective cohort study of patients who received either MRI-Bx or systematic biopsy (SB) within a single academic medical center between January 2018 - June 2020. For each patient, socioeconomic variables including household income, education, percent below poverty, and unemployment were estimated using 2015 American Community Survey census-tract level data. Chi-square analysis was used to examine differences in clinical and demographic characteristics between the two groups. The Benjamini-Hochberg procedure was used to control false discovery rate (FDR) for multiple testing. RESULTS: Eighteen percent of Black men (53/295) received MRI-Bx while 41% (228/561) of white men received MRI-Bx. Patients coming from highly impoverished areas were less likely to receive MRI-Bx, 25% vs 75%, respectively. In multivariate analysis, race remained significantly different across MRI-Bx and SB groups. Clinical factors including family history, DRE, BMI, and prostate volume were not significantly different between patients receiving MRI-Bx and SB. CONCLUSION: Black men are less likely to receive MRI-Bx than white men, even after adjusting for clinical and socioeconomic characteristics. Further work is necessary to identify and study methods to increase equity in PCa diagnostic testing.

Genomic analysis of response to bacillus Calmette-Guérin (BCG) treatment in high-grade stage 1 bladder cancer patients.

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) therapy is standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) but overall efficacy is low, and no reliable predictive biomarkers currently exist to refine patient selection. We performed genomic analysis on high-grade (HG) T1 NMIBCs to determine if response to therapy is predicted by certain mutational and/or expressional changes. METHODS: Patients with HG T1 NMIBC treated with induction BCG were stratified by response into durable and non-durable responders. Baseline tumor samples were subjected to targeted DNA sequencing and whole-exome RNAseq. Genomic variants differing significantly between response groups were analyzed using Ingenuity Pathway Analysis (IPA) software. Variant selection was refined to target potential biomarker candidates for responsiveness to BCG. RESULTS: Among 42 patients, the median follow-up was 51.7 months and 40.5% (n=17) were durable BCG responders. Deleterious mutations in the RNA sequence of JCHAIN, S100A7, CLEC2B, and ANXA10 were more common in non-durable responders. Mutations in MCL1 and MSH6 detected on targeted sequencing were more commonly found in durable responders. Of all deleterious DNA and RNA mutations identified, only MCL1 was significantly associated with longer recurrence free survival (RFS) (P=0.031). CONCLUSIONS: Differences in the genomic profiles of HG T1 NMIBC tumors exist between those who show durable response to BCG and those who do not. Using pathway analysis, those differences imply upregulation of several interconnected inflammatory pathways among responders. Specific variants identified here, namely MCL1, are candidates for further study and, if clinically validated, may serve as useful biomarkers in the future.

Racial Disparities in Prostate Specific Antigen Screening and Referral to Urology in a Large, Integrated Health Care System: A Retrospective Cohort Study.

PURPOSE: Contemporary trends and racial disparities in prostate cancer screening and referral to urology for prostate cancer risk are not well characterized, despite consensus that Black men are at higher risk for poor prostate cancer outcomes. The objective of this study was to characterize current racial disparities in prostate cancer screening and referral from primary care to urology for prostate cancer concern within our large, integrated health care system. MATERIALS AND METHODS: This retrospective cohort study used data from Atrium Health's enterprise data warehouse, which includes patient information from more than 900 care locations across North Carolina, South Carolina and Georgia. We included all men seen in the ambulatory or outpatient setting between 2014 and 2019 who were ≥40 years old. Clinical and demographic data were collected for all men, including age and race. Racial outcomes were reported for all groups with >2% representation in the population. Between-group comparisons were determined using chi-squared analysis, Wilcoxon rank sum testing and multivariable logistic regression, with significance defined as p <0.05. RESULTS: We observed a significant decrease in prostate specific antigen testing across all age and racial groups in a cohort of 606,985 men at Atrium Health, including 87,189 Black men, with an overall relative decline of 56%. As compared to White men, Black men were more likely to undergo prostate specific antigen testing (adjusted OR 1.24, 95% CI 1.22-1.26) and be referred to urology for prostate cancer (adjusted OR 1.94, 95% CI 1.75-2.16). CONCLUSIONS: There was a continued significant decline in prostate cancer screening between 2014 and 2019. Despite having modestly elevated odds of being screened for prostate cancer compared to White men, Black men are relatively underscreened when considering that those who undergo prostate specific antigen screening are more likely to be referred by primary care to urology for additional prostate cancer diagnostic evaluation.

Demographic and Socioeconomic Factors Associated with Urinary Stone Disease Management in a Large Urban US Population.

OBJECTIVE: To determine the influence of socioeconomic parameters on urinary stone surgeries. METHODS: A retrospective cohort study analyzed patients undergoing urolithiasis surgery in our community network hospital in North Carolina from 2005-2018. RESULTS: Of 7731 patients, 2160 (28%), 5,174 (67%), and 397 (5%) underwent SWL, URS, and PCNL, respectively. A higher proportion of Whites underwent URS (67%) and SWL (74%) than PCNL (56%); whereas a larger percentage of Blacks underwent PCNL (24%) than URS (20%) and SWL (15%) groups (P <.001). Private insurance payers were greater in the SWL (95%) group than URS (80%) and PCNL (81%) (P <.001). The distribution of median income was significantly different amongst the 3 surgeries with higher income classes overutilizing SWL and underutilizing PCNL compared to lower income classes (P <.001). In linear regression modeling, the proportion of SWL in a postal code was positively associated with median income (R2=0.55, P <.001); URS and PCNL were negatively associated with median income (R2=0.40, P <.001 and R2=0.41, P <.001, respectively). On multivariate logistic regression modeling, Blacks were significantly more likely to undergo PCNL than Whites (aOR 1.32, 95% CI 1.01-1.74 P <.050). Private insurance payers were more likely to undergo SWL (aOR 11.0, 95% CI 7.26-16.8, P <.0001) than public insurance payers. Patients in higher median income brackets are significantly less likely to undergo PCNL than those in the <$40,000 income bracket (P <.0001). CONCLUSION: Our study suggests that socioeconomic status impacts urolithiasis surgical management, underscoring disparity recognition importance in endourologic care and ensuring appropriate surgical care regardless of socioeconomic status.

Clinical Utility of Postneoadjuvant Chemotherapy Computerized Tomography for Muscle Invasive Urothelial Bladder Cancer.

INTRODUCTION: For muscle invasive bladder cancer, computerized tomography scans are often used before cystectomy to optimize surgical decision planning. The aim of this study is to evaluate the clinical value of postneoadjuvant chemotherapy computerized tomography in patients with localized bladder cancer before cystectomy. METHODS: All T2-3N0 patients with urothelial bladder cancer who completed cisplatin based neoadjuvant chemotherapy were retrospectively analyzed. On postneoadjuvant chemotherapy computerized tomography patients with tumor progression, nodal involvement, metastatic disease and noncancer findings were determined, and subsequent surgical decision making was evaluated. RESULTS: Of 79 cases 21.5% had a new finding on postneoadjuvant chemotherapy scan of which false-positive rates for nodal and metastatic disease were 100%. The frequency of novel findings on postneoadjuvant computerized tomography were 4 (5.1%) with tumor progression, 6 (7.6%) newly discovered enlarged nodes, 8 (10.1%) suspicious for distant metastases and 3 (3.8%) noncancer related conditions. Only 3.8% (3) had alterations in original cystectomy plans exclusively due to tumor progression and 100% of the cohort underwent cystectomy. Overall survival was not associated with new findings (3-year OS 77.4% vs 74%, p=0.473). Median time from postneoadjuvant chemotherapy scan to cystectomy was statistically delayed for patients with new radiographic findings vs those with consistent preneoadjuvant chemotherapy scans (29.5 vs 51 days; p=0.014). CONCLUSIONS: Compared to the preneoadjuvant chemotherapy scans, our data suggests that postneoadjuvant chemotherapy computerized tomography scans discover new findings in approximately 21.5% of cases, but this rarely changes preoperative plans, is not associated with overall survival and is frequently associated with false-positive results.

Association of 5-Alpha Reductase Inhibitor Use with Prostate Specific Antigen Level at the Time of Urology Referral in a Retrospective Cohort at a Large, Integrated Health Care System.

INTRODUCTION: 5-Alpha reductase inhibitor (5-ARI) use leads to a 50% decline in serum prostate specific antigen (PSA) without a concomitant decrease in prostate cancer (PCa) risk. We hypothesize that failure to account for the effect of 5-ARI use on serum PSA leads to increased PCa risk at urology referral among 5-ARI users. METHODS: This is a retrospective cohort study for the years 2018-2019. Atrium Health is a large, vertically integrated health system with over 900 care locations in North Carolina and South Carolina. Men ≥40 years old during 2018-2019 who had a PSA test performed were included. We determined differences in corrected serum PSA level at the time of referral to urology. 5-ARI users and nonusers were compared using the chi-square test, Student's t-test and gamma regression. RESULTS: From 2018-2019, there were 91,368 men who underwent PSA testing, including 2,939 5-ARI users. At referral, 5-ARI users had similar uncorrected median PSA (5.8 vs 5.6 ng/ml, p=0.05). After correcting for the effect of 5-ARIs on PSA, 5-ARI users had a median PSA of 11.6 ng/ml at urology referral, compared to 5.6 ng/ml in nonusers. CONCLUSIONS: Men taking 5-ARIs have higher corrected serum PSA at time of referral to urology. As the unadjusted PSA at referral to urology for PCa risk was similar between 5-ARI users and nonusers, this indicates that the effect of 5-ARI use on serum PSA levels is not routinely accounted for when assessing PCa risk.

Insights From Rapid Deployment of a "Virtual Hospital" as Standard Care During the COVID-19 Pandemic.

BACKGROUND: Pandemics disrupt traditional health care operations by overwhelming system resource capacity but also create opportunities for care innovation. OBJECTIVE: To describe the development and rapid deployment of a virtual hospital program, Atrium Health hospital at home (AH-HaH), within a large health care system. DESIGN: Prospective case series. SETTING: Atrium Health, a large integrated health care organization in the southeastern United States. PATIENTS: 1477 patients diagnosed with coronavirus disease 2019 (COVID-19) from 23 March to 7 May 2020 who received care via AH-HaH. INTERVENTION: A virtual hospital model providing proactive home monitoring and hospital-level care through a virtual observation unit (VOU) and a virtual acute care unit (VACU) in the home setting for eligible patients with COVID-19. MEASUREMENTS: Patient demographic characteristics, comorbid conditions, treatments administered (intravenous fluids, antibiotics, supplemental oxygen, and respiratory medications), transfer to inpatient care, and hospital outcomes (length of stay, intensive care unit [ICU] admission, mechanical ventilation, and death) were collected from electronic health record data. RESULTS: 1477 patients received care in either the AH-HaH VOU or VACU or both settings, with a median length of stay of 11 days. Of these, 1293 (88%) patients received care in the VOU only, with 40 (3%) requiring inpatient hospitalization. Of these 40 patients, 16 (40%) spent time in the ICU, 7 (18%) required ventilator support, and 2 (5%) died during their hospital admission. In total, 184 (12%) patients were ever admitted to the VACU, during which 21 patients (11%) required intravenous fluids, 16 (9%) received antibiotics, 40 (22%) required respiratory inhaler or nebulizer treatments, 41 (22%) used supplemental oxygen, and 24 (13%) were admitted as an inpatient to a conventional hospital. Of these 24 patients, 10 (42%) required ICU admission, 1 (3%) required a ventilator, and none died during their hospital admission. LIMITATION: Generalizability is limited to patients with a working telephone and the ability to comply with the monitoring protocols. CONCLUSION: Virtual hospital programs have the potential to provide health systems with additional inpatient capacity during the COVID-19 pandemic and beyond. PRIMARY FUNDING SOURCE: Atrium Health.

Epidemiology and survival outcome of adult kidney, bladder, and prostate rhabdomyosarcoma: A SEER database analysis.

Rhabdomyosarcoma (RMS) is rare in adulthood, accounting for 2%-5% of adult soft tissue tumors, and less than 20% occur in genitourinary organs. Given its rarity, survival data on adult kidney, bladder, and prostate RMSs is limited. In this population-based analysis, we performed an analysis of all adult RMS cases reported in Surveillance, Epidemiology, and End Results (SEER) database to understand prognostic factors among kidney, bladder, and prostate RMS. A query of the SEER database was performed from 1973 to 2016 for patients >18 of age with RMS. The final cohort consisted of 14 kidney, 35 bladder, and 21 prostate RMS cases in the adult population. Demographic, treatment, and survival data were obtained. Analysis was performed using Fisher's exact test, survival analysis, and model. The median (range) age of diagnosis for adult bladder RMS was 65 years old (19-84) compared to 52.5 (28-68) and 42 (19-87) for kidney and prostate (p = 0.007). About 78.6% of patients underwent surgical intervention. Five-year overall survival (OS) for adult kidney, bladder, and prostate RMS are 17.1% (2.9-41.6%), 22.2% (9.4-38.4%), and 33.0 (12.8-55.0%), respectively. OS was not statistically associated with primary site (p = 0.209). On multivariable analysis, compared to adult bladder RMS, kidney RMS had a higher incidence of mortality (HR: 2.16, 95% CI 1.03-4.53, p = 0.041). Incidence of mortality from prostate RMS was not significantly different from bladder RMS (HR: 0.70, 95% CI 0.30-1.65, p = 0.411). Extent of disease (HR: 5.17, 95% CI 2.09-12.79, p < 0.001) and older age (HR 1.03, 95% CI 1.01-1.04, p = 0.002) were adverse prognostic factors for OS. Overall survival at 5 years for adult kidney, bladder, and prostate RMS is poor. Localized disease and younger age are prognostic factors for improved outcomes in adult RMS. Hence, early diagnosis and intervention appear paramount to improved survival for this rare malignancy in adulthood.

The development and comparative effectiveness of a patient-centered prostate biopsy report: a prospective, randomized study.

PURPOSE: The prostate biopsy pathology report represents a critical document used for decision-making in patients diagnosed with prostate cancer, yet the content exceeds the health literacy of most patients. We sought to create and compare the effectiveness of a patient-centered prostate biopsy report compared with standard reports. MATERIALS AND METHODS: Using a modified Delphi approach, prostate cancer experts identified critical components of a prostate biopsy report. Patient focus groups provided input for syntax and formatting of patient-centered pathology reports. Ninety-four patients with recent prostate biopsies were block randomized to the standard report with or without the patient-centered report. We evaluated patient activation, self-efficacy, provider communication skills, and prostate cancer knowledge. RESULTS: Experts selected primary and secondary Gleason score and the number of positive scores as the most important elements of the report. Patients prioritized a narrative design, non-threatening language and information on risk classification. Initial assessments were completed by 87% (40/46) in the standard report group and 81% (39/48) in the patient-centered report group. There were no differences in patient activation, self-efficacy, or provider communication skills between groups. Patients who received the patient-centered report had significantly improved ability to recall their Gleason score (100% vs. 85%, p = 0.026) and number of positive cores (90% vs. 65%, p = 0.014). In total, 86% of patients who received the patient-centered report felt that it helped them better understand their results and should always be provided. CONCLUSIONS: Patient-centered pathology reports are associated with significantly higher knowledge about a prostate cancer diagnosis. These important health information documents may improve patient-provider communication and help facilitate shared decision-making among patients diagnosed with prostate cancer.

Self-Identified African Americans and prostate cancer risk: West African genetic ancestry is associated with prostate cancer diagnosis and with higher Gleason sum on biopsy.

Concerns about overtreatment of clinically indolent prostate cancer (PrCa) have led to recommendations that men who are diagnosed with low-risk PrCa be managed by active surveillance (AS) rather than immediate definitive treatment. However the risk of underestimating the aggressiveness of a patient's PrCa can be a significant source of anxiety and a barrier to patient acceptance of AS. The uncertainty is particularly keen for African American (AA) men who are about 1.7 times more likely to be diagnosed with PrCa than European American (EA) men and about 2.4 times more likely to die of this disease. The AA population, as many other populations in the Americas, is genetically heterogeneous with varying degrees of admixture from West Africans (WAs), Europeans, and Native Americans (NAs). Recommendations for PrCa screening and management rarely consider potential differences in risk within the AA population. We compared WA genetic ancestry in AA men undergoing standard prostate biopsy who were diagnosed with no cancer, low-grade PrCa (Gleason Sum 6), or higher grade PrCa (Gleason Sum 7-10). We found that WA genetic ancestry was significantly higher in men who were diagnosed with PrCa on biopsy, compared to men who were cancer-negative, and highest in men who were diagnosed with higher grade PrCa (Gleason Sum 7-10). Incorporating WA ancestry into the guidelines for making decisions about when to obtain a biopsy and whether to choose AS may allow AA men to personalize their approach to PrCa screening and management.

Pathologic Nodal Involvement in Patients With Penile Cancer With Cavernosal Versus Spongiosal Involvement.

BACKGROUND: The American Joint Committee on Cancer recently proposed new TNM staging for penile cancer, with proposed T2 as spongiosal invasion and T3 as cavernosal invasion. We sought to validate the proposed staging system for predicting pathologic nodal involvement using the National Cancer Data Base. PATIENTS AND METHODS: Invasive penile cancer cases from 2010 to 2012 were identified. Differences in demographic and pathologic factors between T2 and T3 tumors were compared using χ2 and t tests. Logistic regression was performed to determine the odds of pathologically involved lymph nodes (pN+) by T classification. RESULTS: There were 378 T2 and 524 T3 patients with penile cancer. Compared with T2 tumors, T3 tumors were larger (mean size, 5.8 cm vs. 4.3 cm), had higher positive surgical margin rates (12% vs. 9%), and were more likely to have lymphovascular invasion (42% vs. 31%) (all P < .05). In multivariable analysis, both T2 (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.3) and T3 (OR, 2.3; 95% CI, 1.4-3.6) remained significantly associated with risk of positive lymph nodes compared with T1 disease, but there was no increase in risk between T2 and T3 disease (OR, 1.1; 95% CI, 0.7-1.8; P = .56). CONCLUSION: The proposed new American Joint Committee on Cancer staging system for the penile cancer distinguishes spongiosal (T2) from cavernosal (T3) involvement. There does not appear to be a difference in positive lymph node status between the 2 grades when other clinical and pathologic variables are considered.

Continued 5α-Reductase Inhibitor Use after Prostate Cancer Diagnosis and the Risk of Reclassification and Adverse Pathological Outcomes in the PASS.

PURPOSE: Outcomes in patients who enroll in active surveillance programs for prostate cancer while receiving 5α-reductase inhibitors have not been well defined. We sought to determine the association of 5α-reductase inhibitor use with the risk of reclassification in the PASS (Canary Prostate Active Surveillance Study). MATERIALS AND METHODS: Participants in the multicenter PASS were enrolled between 2008 and 2016. Study inclusion criteria were current or never 5α-reductase inhibitors use, Gleason score 3 + 4 or less prostate cancer at diagnosis, less than a 34% core involvement ratio at diagnosis and 1 or more surveillance biopsies. Included in study were 1,009 men, including 107 on 5α-reductase inhibitors and 902 who had never received 5α-reductase inhibitors. Reclassification was defined as increase in the Gleason score and/or an increase to 34% or greater in the ratio of biopsy cores positive for cancer. Adverse pathology at prostatectomy was defined as Gleason 4 + 3 or greater and/or nonorgan confined disease (pT3 or N1). RESULTS: On multivariable analysis there was no difference in reclassification between men who had received and those who had never received 5α-reductase inhibitors (HR 0.81, p = 0.31). Patients who had received 5α-reductase inhibitors were less likely to undergo radical prostatectomy (8% vs 18%, p = 0.01) or any definitive treatment (19% vs 24%, p = 0.04). In the 167 participants who underwent radical prostatectomy there was no suggestion of a difference in the rate of adverse pathology findings at prostatectomy between 5α-reductase inhibitor users and nonusers. CONCLUSIONS: Continued 5α-reductase inhibitor use after an initial diagnosis of prostate cancer was not associated with the risk of reclassification on active surveillance in men in the PASS cohort.