Men Undergoing Prostate Biopsy Research Articles

Interassay Variability and Clinical Implications of Five Different Prostate-specific Antigen Assays

Background and objectiveProstate-specific antigen (PSA) remains a critical marker for prostate cancer (PCa) detection and monitoring. Recognising historical variability in PSA assays and the evolution of assay technology and calibration, this study aims to reassess interassay variability using the latest generation of five assays in a contemporary cohort of men undergoing prostate biopsy. MethodsFive different commercially available PSA assays were tested in a blood sample of 76 men before undergoing a prostate biopsy. Total PSA (tPSA) and free-to-total PSA ratio (%fPSA) were compared across assays, using Roche (Basel, Switzerland) as the benchmark, and correlated with biopsy outcome to analyse the impact on PCa diagnosis. The statistical analysis included Passing-Bablok regression and Bland-Altman plots, with a p value threshold of <0.05 for significance. Key findings and limitationsAmong the 76 men, 28 (36.8%) were diagnosed with significant PCa (defined as International Society of Urological Pathology grade ≥2). A high correlation was observed between tPSA and %fPSA values among the different PSA assays tested (r2 ≥ 0.9). The Passing-Bablok analysis showed that tPSA results varied substantially among the assays, with slopes ranging between 0.78 and 1.04. Compared with the tPSA of Roche, tPSA values were on average 20.7% lower by Beckman (Oststeinbeck, Germany), 15.2% lower by Abbott (Chicago, IL, USA), 6.1% lower by Diasorin (Saluggia, Italy), and 9.6% higher by Brahms (Hennigsdorf, Germany; p < 0.001 for all). The %fPSA values by Abbott and Brahms were higher at 15.7% and 10.6%, respectively (p < 0.001), while the Beckman and Diasorin values had minimal differences of -0.3% and 2.3%, respectively (p > 0.05). The variability across assays would have resulted in discrepancies in both the sensitivity and the specificity for tPSA and %fPSA by at least 14%, depending on the cut-offs applied. Conclusions and clinical implicationsDespite the use of the latest PSA assays, relevant variability of tPSA and %fPSA results can be observed among different assays. There is an urgent need for standardised calibration methods and greater awareness among practitioners concerning interassay variability. Clinicians should acknowledge that clinically relevant thresholds may depend on the specific PSA assay and that ideally the same assay is applied over time for better clinical decision-making. Patient summaryProstate-specific antigen (PSA) is a critical marker for prostate cancer (PCa) detection and monitoring. However, significant variations were observed in the results of the latest PSA assays. Thus, standardised calibration methods and greater awareness among practitioners concerning interassay variability are needed.

Abstract B025: A multi-omic, spatial approach using patient prostatectomies to identify actionable drug targets for combatting prostate cancer health disparities

Abstract Prostate cancer (PC) is the most commonly diagnosed cancer among African American men (AA) and continues to be the largest difference in absolute incidence and cancer-specific deaths between AA and Caucasian men (CA). AA have a 70% higher incidence of PC than CA and over a 2 times higher mortality rate. Among men undergoing prostate biopsy In an equal access setting (i.e. the VA), AA are ~50% more likely to have PC and ~80% more likely to have high-grade PC than CA. The frequency of PC-associated genetic alterations and differences in oncogene expression in PCs is altered from CA and AA. While social economic status and environmental factors may play a role in PC health disparities, there are inherent genetic/molecular differences that account for the differences in PC outcomes between CA and AA. We sought to test our hypothesis that there is a subset of actionable gene products that are essential for enhanced PC progression in AA. A focused and clinically informed CRISPR knockout screen was conducted to identify and functionally validate race-specific actionable genes that contribute to the increased risks of fatal PC in AA. The CRISPR screen was designed leveraging a radical prostatectomy transcriptomic dataset from the Durham VA Medical Center that was linked with long-term clinical outcome data. This unique dataset consists of ~600-profiled radical prostatectomy samples of which over 50% were from AA patients. A Cox hazard analysis revealed differentially expressed genes (DEGs) which are positively associated with an increased risk of metastatic disease unique to AA PC patients. To identify drug-targetable genes, these DEGs were filtered against the drug-gene interaction database (DGIdb). This approach yielded 89 genes positively associated with an increased risk of metastatic outcome in AA and 236 genes in CA only. The CRISPR KO screen resulted in 19 genes significantly depleted genes. Of these 19 hits, 11 genes were genes associated with metastasis in AA, while 8 hits were CA genes, with 5 of 11 AA hits having documented small molecule inhibitors. To further prioritize our hits, we have conducted a spatial transcriptomic analysis of radical prostatectomy tissues from AA and CA PCs. By standard H and E staining these tumors look quite similar. But spatial analysis of AA compared to CA tissues revealed differences in immune cells and cells associated with the tumor microenvironment. This integrative multi-omic approach reveals new cell identities that may contribute to the aggressive pathogenicity of PC in AA compared to CA. CRISPR models and small molecule inhibitors of our top candidates will be used to investigate the druggability of these DEGs. This study lays the groundwork for potential therapeutics targeted toward PC in AA men. Citation Format: Felipe Segato Dezem, Aiza Akhtar, Arjumand Wanj, Sunyoung You, Hannah Chasteen, So Young Kim, Jasmine Plummer, Everardo Macias. A multi-omic, spatial approach using patient prostatectomies to identify actionable drug targets for combatting prostate cancer health disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B025.

Abstract IA047: A multiomic approach towards identifying actionable targets to combat prostate cancer health disparities

Abstract Prostate cancer (PC) is the most commonly diagnosed cancer among African American men (AA) and continues to be the largest difference in absolute incidence and cancer specific deaths between AA and Caucasian men (CA). AA have a 70% higher incidence of PC than CA and over a 2 times higher mortality rate. Among men undergoing prostate biopsy In an equal access setting (i.e. the VA), AA are ~50% more likely to have PC and ~80% more likely to have high-grade PC than CA. The frequency of PC associated genetic alterations and differences in oncogene expression in PCs is altered from CA and AA. While social economic status and environmental factors may play a role in PC health disparities, there are inherent genetic/molecular differences that account for the differences in PC outcomes between CA and AA. We sought to test our hypothesis that there is subset of actionable gene products that are essential for enhanced PC progression in AA. A focused and clinically informed CRISPR knockout screen was conducted to identify and functionally validate race specific actionable genes that contribute to the increased risks of fatal PC in AA. The CRISPR screen was designed leveraging a radical prostatectomy trancscriptomic dataset from the Durham VA Medical Center that was linked with long-term clinical outcome data. This unique dataset consists of ~600-profiled radical prostatectomy samples of which over 50% were from AA patients. A cox hazard analysis revealed differentially expressed genes (DEGs) which positively associated with increased risk of metastatic disease unique to AA PC patients. To identify drug targetable genes, these DEGs were filtered against the drug gene interaction database (DGIdb).This approach yielded 89 genes positively associated with increased risk of metastatic outcome in AA and 236 genes in CA only. The CRISPR KO screen resulted in 19 genes significantly depleted genes. Of these 19 hits, 11 genes were genes associated with metastasis in AA, while 8 hits were CA genes, with 5 of 11 AA hits have documented small molecule inhibitors. To further prioritize our hits, we have conducted spatial transcriptomic analysis of radical prostatectomy tissues from AA and CA PCs. By standard H and E staining these tumors looking quite similar. But spatial analysis of AA compared to CA tissues revealed differences in immune cells and cells associated with tumor microenvironment. These integative multiomic approach reveals new cell identities that may contribute to the aggressive pathogenicity of PC in AA compared to CA. CRISPR models and small molecule inhibitors of our top candidates will be used in investigate druggability of these DEGs. This study lays the groundwork for potential therapeutics targeted towards PC in AA men. Citation Format: Felipe Dezem, Aiza Akhtar, Sungyong You, So Young Kim, Jasmine Plummer, Everardo Macias. A multiomic approach towards identifying actionable targets to combat prostate cancer health disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA047.

Complications Following Transrectal and Transperineal Prostate Biopsy: Results of the ProBE-PC Randomized Clinical Trial.

Transrectal prostate biopsy has come under scrutiny due to potential for postbiopsy infections and transperineal prostate biopsy is being offered as the safer alternative. However, there is a lack of randomized comparative studies. Our goal was to directly evaluate infectious and noninfectious complications following the 2 biopsy procedures. We conducted a prospective, pragmatic, randomized clinical study in men undergoing prostate biopsy. The participants underwent either transrectal or transperineal prostate biopsy in the office under local anesthesia. The primary outcome was a 30-day composite infectious complication rate, comprising of 1 or more components including fever, genitourinary infection, antibiotic prescriptions, office or emergency visits, hospitalization, or sepsis. Secondary outcomes included 30-day composite noninfectious complications (urinary or hemorrhagic). Of the 763 randomized participants, 718 underwent either transrectal (351) or transperineal (367) prostate biopsy. A composite infectious complication event occurred in 9 participants (2.6%) in the transrectal and 10 participants (2.7%) in the transperineal group (odds ratio, 1.06; 95% CI, 0.43 to 2.65; P = .99). None of the participants developed sepsis in either group. There were no between-group differences in any of the individual component infectious events. A composite noninfectious complication occurred in 6 (1.7%) and 8 (2.2%) participants in the transrectal and transperineal groups, respectively (odds ratio, 1.28; 95% CI, 0.44 to 3.73; P = .79). No participants required hospitalization or other interventions. Among men undergoing transperineal or transrectal prostate biopsy, we could not demonstrate any difference in the infectious or noninfectious complications. Both biopsy approaches remain clinically viable and safe.

A cost-effective transperineal prostate biopsy method utilizes the original transrectal setting.

Transperineal prostate biopsy (TPB) offers an alternative to transrectal prostate biopsy (TRB) for prostate cancer diagnosis. However, TPB may result in additional disposable and capital equipment costs, which can limit implementation within urology practice. Herein, we report the initial experience of a novel TPB technique within a tertiary referral center in Taiwan. A retrospective review of all men undergoing prostate biopsy January to October in 2021 was performed. Both biopsy techniques were performed with the same setting using the convex-convex array ultrasound probe under local anesthesia alone or with the addition of sedation using double free-hand technique. Complications within 30days and cancer detection rate (CDR) were compared between the groups. A total of 118 biopsies were included for final analysis. Eleven patients received systematic biopsy with additional MRI-targeted biopsy (TB) cores with all performed via a transperineal approach. The TPB group (n = 47) and TRB group (n = 58) had similar CDR after excluding TB cores (46.8% vs. 44.8%, p = 0.675). General complication rates for TPB were significantly lower than in the TRB group (27.7% vs. 46.6%, p = 0.047). No patients undergoing TPB had infectious complications, where five episodes were recorded in the TRB group (p = 0.114). TPB performed with convex-convex ultrasound probe and double free-hand technique is safe, feasible, cost-effective, and demonstrates equivalent CDR to TRB. Its use may eliminate infectious hospitalizations while minimizing the need for additional capital in the adoption of TPB.

MP40-09 EXTERNAL VALIDATION OF A MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING VOLUMETRIC MODEL TO PREDICT THE UTILITY OF SYSTEMATIC BIOPSIES AT THE TIME OF TARGETED BIOPSY

You have accessJournal of UrologyCME1 Apr 2023MP40-09 EXTERNAL VALIDATION OF A MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING VOLUMETRIC MODEL TO PREDICT THE UTILITY OF SYSTEMATIC BIOPSIES AT THE TIME OF TARGETED BIOPSY Antonella Ninivaggi, Ugo Falagario, Francesco Guzzi, Vito Mancini, Carlo Bettocchi, Gian Maria Busetto, Luigi Cormio, and Giuseppe Carrieri Antonella NinivaggiAntonella Ninivaggi More articles by this author , Ugo FalagarioUgo Falagario More articles by this author , Francesco GuzziFrancesco Guzzi More articles by this author , Vito ManciniVito Mancini More articles by this author , Carlo BettocchiCarlo Bettocchi More articles by this author , Gian Maria BusettoGian Maria Busetto More articles by this author , Luigi CormioLuigi Cormio More articles by this author , and Giuseppe CarrieriGiuseppe Carrieri More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In this study we aimed to externally validate a nomogram based on MRI volumetric parameters and clinical information for deciding when SBx (Standard Biopsy) should be performed in addition to TBx (Target Biopsy)in men with suspicious prostate MRI. METHODS: We retrospectevely analysed a prospectevely mantained databes of 496 biopsy naïve men undergoing prostate biopsy with a pre-biopsy multiparametric Magnetic Resonance Imaging (mpMRI) at two institutions. Prostate MRI was performed according to PI-RADS recommendations including T1-wighted (T1WI) and T2-weighted images (T2WI), diffusion weighted images (DWI) with apparent diffusion coefficient (ADC) maps, and dyamic contrast enhances images (DCEI). Men with PIRADSsv 2.1 score of 3-5 were included. All patients underwent MRI-Ultrasound Fusion biopsy of each MRI-suspicious lesion and a fourteen-systematic biopsy according to our protocol. Lesion volume percentage was computed as the ratio of cancer volume on MRI divided the whole prostate volume. Outcomes of this study were non-clinically significant PCa (ncsPCa) (Gleason Grade Group 1) and clinically significant PCa (csPCa) (Gleason Grade Group >1). The model was evaluated with AUC (Area Under the Curve) decision curve analyses and a systematic analysis of model derived probability cut-offs in terms of number of ncsPCa diagnosis avoidance and number of csPCa diagnosed. RESULTS: The nomogram includes age, PSA value, prostate volume, PIRADSsv2.1 score, MRI-suspicion lesion volume percentage, and lesion location. The AUC was 0.73. Using different nomogram cut-offs (from 5% to 30%), 19-58% of men would avoided SBx while missing 0-10% of csPCA and avoiding detection of 6-31% of ncsPCa. These results are similar to those found in the multi-insitutional external validation study based on IMPROD trial (n=122) and MULTI-IMPROD trial (n=262). Decision Curve Analysis (DCA) shows that this nomogram increases the overall net clinical benefit when threshold probability is above 10%. CONCLUSIONS: The present study supports the potential utility of a model based on MRI volumetrics for the selection of men with a clinical suspicion of prostate cancer who would benefit of SBx in addition to TBx. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e548 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Antonella Ninivaggi More articles by this author Ugo Falagario More articles by this author Francesco Guzzi More articles by this author Vito Mancini More articles by this author Carlo Bettocchi More articles by this author Gian Maria Busetto More articles by this author Luigi Cormio More articles by this author Giuseppe Carrieri More articles by this author Expand All Advertisement PDF downloadLoading ...

LBA03-03 INFECTIOUS AND NON-INFECTIOUS COMPLICATIONS FOLLOWING PROSTATE BIOPSY: A RANDOMIZED CLINICAL TRIAL

You have accessJournal of UrologyCME1 Apr 2023LBA03-03 INFECTIOUS AND NON-INFECTIOUS COMPLICATIONS FOLLOWING PROSTATE BIOPSY: A RANDOMIZED CLINICAL TRIAL Badar M. Mian, Paul J. Feustel, Asef Aziz, Ronald Kaufman, Svetlana Avulova, Adrien Bernstein, and Hugh Fisher Badar M. MianBadar M. Mian More articles by this author , Paul J. FeustelPaul J. Feustel More articles by this author , Asef AzizAsef Aziz More articles by this author , Ronald KaufmanRonald Kaufman More articles by this author , Svetlana AvulovaSvetlana Avulova More articles by this author , Adrien BernsteinAdrien Bernstein More articles by this author , and Hugh FisherHugh Fisher More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003426.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate biopsy for cancer detection may be performed either through transrectal (TR-Bx) or transperineal (TP-Bx) approach. Recently, TP-Bx approach is being promoted as the superior alternative to TR-Bx due to potentially lower complication rates. However, there are conflicting clinical guidelines regarding the preferred option, and high level comparative evidence is lacking. We conducted a randomized clinical trial, sufficiently powered to determine if TP-Bx is associated with lower risk of infectious and other complications (ClinicalTrials.gov: NCT04081636). METHODS: 763 men undergoing prostate biopsy were recruited for the randomized study comparing TR-Bx and TP-Bx procedures. All procedures were performed in the office, under local anesthesia. The primary outcome was the 30-day incidence of post-biopsy composite infectious complications (including fever, antibiotic prescriptions, genitourinary infection, sepsis, office or emergency room visits, or hospitalization). Secondary outcome was the 30-day post-biopsy composite non-infectious complication rate (including urinary retention, any hemorrhage requiring intervention, or unplanned heath care utilization). Follow up and data collection included clinic visit at 2 weeks, phone survey at 30 day, and medical record review after 30 days. RESULTS: 718 men completed either the TR-Bx (351) or the TP-Bx (367) procedure and the required follow up. The mean (±SD) age was 64.7 (6.9) years. A composite infectious complication event occurred in 9 patients (2.6%) in the TR-Bx group, and 10 patients (2.7%) in the TP-Bx group (risk ratio 1.06; 95% CI, 0.43 to 2.65; p=0.99). Fever was the most frequent event, reported by 6 patients (1.7%) in each group. Overnight hospitalization required for 2 patients (0.55%) in TR-Bx and 1 patient (0.27%) in TP-Bx group. There were no episodes of sepsis in either group. There were no between-group differences in the occurrence of any of the component outcomes. A composite non-infectious event occurred in 6 (1.7%) and 8 (2.2%) patients in the TR-Bx and TP-Bx groups, respectively (OR 1.28; 95% CI, 0.44 to 3.73; p=0.79). Phone call to the office was the most frequent event that was noted in 3 patients (0.9%) in the TR-Bx and 7 patients (1.9%) in TP-Bx group. Urinary retention occurred in 1 patient in each group, and no patients required hospitalization. CONCLUSIONS: Among men undergoing biopsy for prostate cancer detection, transrectal and transperineal prostate biopsy procedures are associated with a similar risk of infectious and non-infectious complications. Source of Funding: Capital Region Medical Research Institute, SUNY-School of Public Health © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1192 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Badar M. Mian More articles by this author Paul J. Feustel More articles by this author Asef Aziz More articles by this author Ronald Kaufman More articles by this author Svetlana Avulova More articles by this author Adrien Bernstein More articles by this author Hugh Fisher More articles by this author Expand All Advertisement PDF downloadLoading ...

MP40-19 WEST-AFRICAN ANCESTRY CAN AID PREDICTION OF HIGH-GRADE PROSTATE CANCER IN BLACK-TAILORED RISK CALCULATOR

You have accessJournal of UrologyCME1 Apr 2023MP40-19 WEST-AFRICAN ANCESTRY CAN AID PREDICTION OF HIGH-GRADE PROSTATE CANCER IN BLACK-TAILORED RISK CALCULATOR Neil Mistry, Zequn Sun, Norma Marshall, Rick Kittles, Edward Schaeffer, Peter Gann, and Adam Murphy Neil MistryNeil Mistry More articles by this author , Zequn SunZequn Sun More articles by this author , Norma MarshallNorma Marshall More articles by this author , Rick KittlesRick Kittles More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , Peter GannPeter Gann More articles by this author , and Adam MurphyAdam Murphy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Kaiser Permanent Prostate Cancer (KPPC), Prostate Cancer Prevention Trial (PCPT) and Prostate Biopsy Collaborative Group (PBCG) risk calculators (RCs) improve the detection of high-grade, Gleason Grade Group ≥2 prostate cancer (HGPCa) but result in excessive biopsies in Black men. Genetic West African Ancestry (WA) is associated with increased risk of HGPCa, but its impact on RC accuracy is unknown. We aimed to validate a tailored RC to improve accuracy and assess if WA can augment accuracy. METHODS: We recruited men undergoing prostate biopsy from 5 Chicago clinics from 2009-2014. We split the sample into development (75%) and validation (25%) cohorts. A second cohort from the same sites from 2016-2019 provided external validation. Exclusion criteria were non-Black race and PSA >50 ng/ml. We created 2 binary logistic regressions to predict HGPCa using clinical variables alone and including WA. Model accuracy was assessed using area under curve (AUC). RESULTS: 393 Black men were included for development/internal validation, and 354 for external validation. Table 1 shows model performance and comparisons to prior RCs. CONCLUSIONS: A tailored RC improves HGPCa prediction in Blacks compared to popular RCs. Including genetic ancestry as a risk factor alongside clinical variables may help alleviate PCa disparities faced by Black men. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e553 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neil Mistry More articles by this author Zequn Sun More articles by this author Norma Marshall More articles by this author Rick Kittles More articles by this author Edward Schaeffer More articles by this author Peter Gann More articles by this author Adam Murphy More articles by this author Expand All Advertisement PDF downloadLoading ...

Prevalence of genotoxic bacteria in men undergoing biopsy for prostate cancer.

New evidence suggests that bacteria-produced DNA toxins may have a role in the development or progression of prostate cancer. To determine the prevalence of these genes in a noninfection (i.e., colonized) state, we screened urine specimens in men before undergoing a biopsy for prostate cancer detection. We developed a multiplex polymerase chain reaction using three of the most described bacterial genotoxin gene primers: Colibactin (polyketone synthase[pks] gene island: clbN and clbB), cytotoxic necrotizing factor (cnf1) toxin, and cytolethal distending toxin B (cdtB) represented gene islands. After calibration on Escherichiacoli samples of known genotypes, we used a training and validation cohort. We performed multiplex testing on a training cohort of previously collected urine from 45 men undergoing prostate biopsy. For the validation cohort, we utilized baseline urine samples from a previous randomized clinical trial (n = 263) with known prostate cancer outcomes. The prevalence of four common bacterial genotoxin genes detected in the urine before prostate biopsy for prostate cancer is 8% (25/311). The prevalence of pks island (clbN and clbB), cnf1, and cdt toxin genes are 6.1%, 2.4%, and 1.7%, respectively. We found no association between urinary genotoxins and prostate cancer (p = 0.83). We did identify a higher proportion of low-grade cancer (92% vs. 44%) in those men positive for urinary genotoxin and higher-grade cancer in those genotoxin negative (8% vs. 56%, p = 0.001). The prevalence of urinary genotoxins is low and does not correspond to a prostate cancer diagnosis. The urine was taken at one point in time and does not rule out the possibility of previous exposure.

The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy

To date, the combined effect of polygenic risk score (PRS) and prostate health index (phi) on PCa diagnosis in men undergoing prostate biopsy has never been investigated. A total of 3166 patients who underwent initial prostate biopsy in three tertiary medical centers from August 2013 to March 2019 were included. PRS was calculated on the basis of the genotype of 102 reported East-Asian-specific risk variants. It was then evaluated in the univariable or multivariable logistic regression models that were internally validated using repeated 10-fold cross-validation. Discriminative performance was assessed by area under the receiver operating curve (AUC) and net reclassification improvement (NRI) index. Compared with men in the first quintile of age and family history adjusted PRS, those in the second, third, fourth, and fifth quintiles were 1.86 (odds ratio, 95% confidence interval (CI): 1.34-2.56), 2.07 (95%CI: 1.50-2.84), 3.26 (95%CI: 2.36-4.48), and 5.06 (95%CI: 3.68-6.97) times as likely to develop PCa (all p < 0.001). Adjustment for other clinical parameters yielded similar results. Among patients with prostate-specific antigen (PSA) at 2-10 ng/mL or 2-20 ng/mL, PRS still had an observable ability to differentiate PCa in the group of prostate health index (phi) at 27-36 (Ptrend < 0.05) or >36 (Ptrend ≤ 0.001). Notably, men with moderate phi (27-36) but highest PRS (top 20% percentile) would have a comparable risk of PCa (positive rate: 26.7% or 31.3%) than men with high phi (>36) but lowest PRS (bottom 20% percentile positive rate: 27.4% or 34.2%). The combined model of PRS, phi, and other clinical risk factors provided significantly better performance (AUC: 0.904, 95%CI: 0.887-0.921) than models without PRS. Adding PRS to clinical risk models could provide significant net benefit (NRI, from 8.6% to 27.6%), especially in those early onset patients (NRI, from 29.2% to 44.9%). PRS may provide additional predictive value over phi for PCa. The combination of PRS and phi that effectively captured both clinical and genetic PCa risk is clinically practical, even in patients with gray-zone PSA.

Abstract C088: Biological and neighborhood-level social determinants of prostate disease aggressiveness among Black and White men undergoing prostate biopsy

Abstract Introduction and study purpose: Prostate cancer (PCa) is the leading type of newly diagnosed cancer and second leading cause of cancer death in American men. Significant racial differences in PCa incidence and mortality have been long-reported in the U.S., with Black men demonstrating a disproportionately higher burden of disease compared to White men. Though some studies conducted in equal access health care settings have revealed equivalent PCa characteristics at diagnosis and comparable PCa outcomes for White and Black men. Identification of early predictors of prostate disease aggressiveness is essential to avoid over-treatment of clinically favorably disease that is unlikely to progress. This study examines the independent and joint roles of biological and social determinants of health (SDOHs) in predicting prostate disease aggressiveness in a racially diverse cohort of men undergoing biopsy for suspicion of PCa. Methodology: A retrospective cohort study was conducted at the University Hospitals Seidman Cancer Center in Cleveland, Ohio for the period January 1, 2005-May 2022. A retrospective chart review was conducted to identify eligible men, including White and Black men undergoing transrectal ultrasound-guided biopsy whose biopsy results included the following 3 groups: (i) negative biopsy with a history of 1+ negative biopsy (-ies) and no history of prostate cancer; (ii) biopsy-detected PCa of Gleason sum 6; and (iii) biopsy-detected PCa with metastases at initial cancer detection. Detailed clinical and biological specimen data were abstracted during retrospective chart review, and quantitative proteomics analysis of biopsy tissues is ongoing, using mass spectrometry, at the Pacific Northwest National Laboratory (PNNL). Multi-level modeling will be conducted to predict prostate disease aggressiveness as a function of protein biomarker candidates in combination with census block group-level SDOHs. Results: This study has achieved its initial goal of assembling a study cohort of 300 eligible men with available biopsy tissue, necessary clinical information, and full street address for assigning census regions. To date, proteomics data have been generated on the first 60 men (“Discovery cohort”) and SDOHs metrics have been linked to the first 180 men. Proteomic profiles and SDOH data will be examined jointly with SDOHs to predict patient clinical phenotype (i.e., metastatic, biopsy Gleason 6, biopsy negative). Conclusions: Identifying new markers of cancer aggressiveness within and across race has the potential to tailor disease management, and identify patients who are likely to benefit from earlier, timely treatment interventions, which will ultimately improve prostate cancer outcomes and quality of life. Predictive modeling that jointly considers biological determinants of cancer disparities in conjunction with neighborhood-level social factors have the potential to elucidate who can be safely spared repeat biopsies, as well as how to optimize cancer care. Citation Format: Jennifer Cullen, Tao Liu, Karin Rodland, Ranjini Ghosh, Anood Alfamy, Julia Payne, Kirsten Eom, Sweta Balaji, Nicole Diaz, Holly Hartman, Annie Liang Zhang, Daniel Spratt, Jonathan Shoag, Erika Trapl, Lee Ponsky, Gregory MacLennan. Biological and neighborhood-level social determinants of prostate disease aggressiveness among Black and White men undergoing prostate biopsy [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C088.

Metabolic syndrome is associated with aggressive prostate cancer regardless of race.

Recent meta-analyses suggest the Metabolic Syndrome (MS) increases high-grade prostate cancer (PC), although studies are inconsistent and few black men were included. We investigated MS and PC diagnosis in black and white men undergoing prostate biopsy in an equal access healthcare system. We hypothesized MS would be linked with aggressive PC, regardless of race. Among men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, medical record data abstraction of diagnosis or treatment for hypertension (≥ 130/85mmHg), dyslipidemia (HDL < 40mg/dL), hypertriglyceridemia (≥ 150mg/dL), diabetes, hyperglycemia (fasting glucose ≥ 100ml/dL), and central obesity (waist circumference ≥ 40 inches) were done. Biopsy grade group (GG) was categorized as low (GG1) or high (GG2-5). Multinomial logistic regression was used to examine MS (3-5 components) vs. no MS (0-2 components) and diagnosis of high grade and low grade vs. no PC, adjusting for potential confounders. Interactions between race and MS were also tested. Of 1,051 men (57% black), 532 (51%) had MS. Men with MS were older, more likely to be non-black, and had a larger prostate volume (all p ≤ 0.011). On multivariable analysis, MS was associated with high-grade PC (OR = 1.73, 95% CI 1.21-2.48, p = 0.003), but not overall PC (OR = 1.17, 95% CI 0.88-1.57, p = 0.29) or low grade (OR = 0.87, 95% CI 0.62-1.21, p = 0.39). Results were similar in black and non-black men (all p-interactions > 0.25). Our data suggest that metabolic dysregulation advances an aggressive PC diagnosis in both black and non-black men. If confirmed, prevention of MS could reduce the risk of developing aggressive PC, including black men at higher risk of PC mortality.

Evaluation of Initial 24-core Transrectal Prostate Biopsy on the Detection of Significant Prostate Cancer and High-grade Prostatic Intraepithelial Neoplasia

Abstract Purpose: The purpose of the study was to assess the diagnostic value of an initial 24-sample transrectal ultrasound-guided (TRUS) prostate biopsy protocol compared to the 10-core technique. Materials and Methods: We retrospectively reviewed the prostate biopsy database of consecutive men undergoing prostate biopsies under local anesthesia using the 10 (Group A) and 24 (Group B) protocols. Men were stratified according to biopsy protocol and prostate-specific antigen (PSA) levels. Exclusion criteria were age = 75 years and PSA &gt;20 ng/mL. The Mann–Whitney U and Fisher’s exact test were used for statistical analysis. Results: Between November 2018 and August 2020, 169 men underwent TRUS prostate biopsies. Group A (10-cores) consisted of 105 (62.13%) men and Group B (24-cores) included 64 (37.86%) men. The overall prostate cancer detection rate was 41.05% and 36.72% in Groups A and B, respectively (P = 0.48). An overall 9.8% increase in Gleason 7 detection rate was found in Group B (P = 0.24). The high-grade prostatic intraepithelial neoplasia (HGPIN) detection rate in men with negative initial biopsies was 15.54% and 35.55% in Groups A and B, respectively (P &lt; 0.001). In patients with PSA &lt;10 ng/mL, the 24-core technique increased Gleason 7 detection rate by 13.4% (P = 0.16) and HGPIN by 23.4% (P = 0.0008), compared to the 10-core technique. The 24-core technique increased the concordance between needle biopsy and prostatectomy specimen compared to the 10-core technique (P &lt; 0.002). Conclusions: The initial 24-core prostate biopsy protocol did not show any benefit in the detection of prostate cancer compared to the 10-core technique. However, it improved the HGPIN detection and the correlation between biopsy results and radical prostatectomy Gleason score in men with lower PSA levels.

Patient engagement in a mobile health intervention to improve preparedness for prostate biopsy.

We designed and implemented a peri-procedural text message (SMS) program for patients undergoing transrectal prostate biopsy and aimed to evaluate predictors of patient enrollment and engagement with the SMS program. We designed an SMS-based program with 8 messages containing web-based modules with educational content and reminders confirming MRI for fusion biopsy, antibiotic adherence, enema use, and anticoagulation cessation. Data on patient demographics, enrollment, and engagement with modules were collected from June 1, 2018 to February 28, 2021. Engagement was defined as a patient clicking a link delivered via SMS to access modules. We made multivariable models to identify predictors of patient enrollment and engagement. Of the 1,760 prostate biopsies between June 2018 and March 2021, 1,383 (78.6%) were enrolled in SMS, 182 (10.3%) in email, 106 (6.0%) in both, and 240 (13.6%) were not enrolled. Of 1418 patients enrolled, 1,270 (89.6%) engaged with at least one module. African American patients had 50% lower odds of being enrolled (OR = 0.50, 95% CI 0.28-0.96; P = 0.03), but once enrolled there were no differences in engagement. Patients for whom English was not listed as their primary language had 60% lower odds of engagement (OR = 0.40, 95% CI 0.17-1.00, P = .04) and patients who were single or divorced had a 40% lower odds of engagement (OR = 0.60, 95% CI 0.41-0.91, P = 0.01). A cohort of older men undergoing prostate biopsy were able to engage with a text message-based education and reminder program. Future efforts must address barriers to enrollment for Black or African American men and improve accessibility to non-English speaking patients.

Racial differences in circulating mitochondria-derived peptides may contribute to prostate cancer health disparities.

The mitochondrial genome has small open reading frames (sORF) which produce measurable mitochondrial-derived peptides (MDPs), including humanin, SHLP2, and MOTS-c. Previously, among men undergoing prostate biopsy, we found higher serum SHLP2 was linked with lower prostate cancer(PC) risk in European American men (EAM), while null associations were found in African American men (AAM). Here, in different patients undergoing prostate biopsy, we tested the link between SHLP2, humanin and MOTS-c and PCrisk by race. Plasma SHLP2, humanin, and MOTS-c were measured in 198 men (50/49 EAM/AAM cases; 50/49 EAM/AAM controls) undergoing biopsy. Logistic and multinomial regression models tested associations between each MDP and PC diagnosis, low-grade (grade group, GG1) and high-grade (GG2-5). Models were adjusted for age, body mass index, digital rectal examination, and prostate specific antigen (PSA). We tested interactions between MDPs and race. Among controls, humanin was similar by race (p = 0.60), but both SHLP2 (p = 0.007) and MOTS-c (p = 0.026) were lower in AAM controls versus EAM controls. Among EAM, higher MDP values were associated with lower PC risk (all p ≤ 0.001), with null associations in AAM (all p-interactions ≤ 0.01). Similarly, higher MDP expression was associated with decreased risk of low- and high-grade PC in EAM (all p ≤ 0.005) with null associations in AAM. Higher MDP levels were associated with lower PC risk in EAM but not AAM. Generally, AAM controls had lower MDP levels. These data support MDPs and mitochondrial dysfunction in PC, suggesting greater dysfunction in AAM may contribute to excess PC risk. Future larger studies are needed to confirm these results.

MP16-13 CAN WE USE THE PROSTATE HEALTH INDEX TO AVOID A PROSTATE BIOPSY IN AFRICAN AMERICAN MEN?

You have accessJournal of UrologyCME1 May 2022MP16-13 CAN WE USE THE PROSTATE HEALTH INDEX TO AVOID A PROSTATE BIOPSY IN AFRICAN AMERICAN MEN? Kostantinos Morris, Srinath Kotamarti, and Judd Moul Kostantinos MorrisKostantinos Morris More articles by this author , Srinath KotamartiSrinath Kotamarti More articles by this author , and Judd MoulJudd Moul More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002549.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: African American (AA) race is a well-known risk factor for prostate cancer (PCa). However, the aggressive push to maximize detection of clinically significant cancer (CSC) is inevitably prone to high rates of over-biopsy. Prostate Health Index (PHI) is a Food and Drug Administration-approved tool to aid in the diagnosis of PCa in men with PSA 4-10 ng/ml. We sought to assess the effectiveness of PHI to avoid a prostate biopsy in AA men with an equivocal PSA. METHODS: Within the Duke Health System, AA men undergoing prostate biopsy with a PSA 4-10 ng/ml and PHI scores from 2016-2020 were identified. The cohort was analyzed for a PHI score cutoff for which 10% or less of men would be identified with CSC, defined as Gleason score ≥7. Representative 95% confidence intervals (CI) were calculated along with cancer detection rates. ROC curves for all PCa and CSC at biopsy were used to identify the area under the curve (AUC) and the diagnostic value of the proposed cutoff point. RESULTS: A total of 236 AA men with an average age of 61.2 years met inclusion criteria out of the 1,131 men who had PHI testing during the study period. Mean PHI and PSA for the entire cohort were 48.5 (SD 21.6) and 6.5 ng/ml (SD 1.7), respectively. Using the established lowest PHI cutoff of 27 led to six of 25 (24.0%) men diagnosed with CSC and 12 of 25 (48%) diagnosed with all PCa. Below a proposed PHI level of 23, one of 12 men were diagnosed with CSC (8.3% [CI: 0.002 – 0.385]) and two of 12 men were diagnosed with any PCa (16.7% [CI: 0.021 – 0.484]). Overall, PHI showed an AUC for all PCa and CSC of 0.705 (0.636 – 0.774) and 0.688 (0.621 – 0.755), respectively. PHI cut point of 23 was associated with a 98.7% sensitivity for all PCa and 99.0% for CSC, at a cost of specificities of 11.8% and 8.4%, respectively. Using this cut point 11 negative biopsies could be avoided, equating to 4.7% of the cohort. CONCLUSIONS: The currently accepted lowest PHI cut point leads to an excessively high rate of PCa in this cohort of AA men. Alternatively, men with a PHI below a proposed cutoff of 23 had optimally low rates of cancer detection and excellent sensitivity to minimize false negative biopsies. While our cohort is the largest reported of AA men undergoing PHI, further validation is needed to confirm these findings. Though generally at higher risk, AA men with an equivocal PSA and a PHI below 23 should be considered candidates to avoid a prostate biopsy. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e280 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kostantinos Morris More articles by this author Srinath Kotamarti More articles by this author Judd Moul More articles by this author Expand All Advertisement PDF DownloadLoading ...

Individualised non-contrast MRI-based risk estimation and shared decision-making in men with a suspicion of prostate cancer: protocol for multicentre randomised controlled trial (multi-IMPROD V.2.0)

IntroductionEuropean Association of Urology and UK National Institute for Health and Care Excellence guidelines recommend that all men with suspicions of prostate cancer should undergo prebiopsy contrast enhanced, that is,...

Defining the Impact of Family History on Detection of High-grade Prostate Cancer in a Large Multi-institutional Cohort

BackgroundThe risk of high-grade prostate cancer, given a family history of cancer, has been described in the general population, but not among men selected for prostate biopsy in an international cohort. ObjectiveTo estimate the risk of high-grade prostate cancer on biopsy based on a family history of cancer. Design, setting, and participantsThis is a multicenter study of men undergoing prostate biopsy from 2006 to 2019, including 12 sites in North America and Europe. All sites recorded first-degree prostate cancer family histories; four included more detailed data on the number of affected relatives, second-degree relatives with prostate cancer, and breast cancer family history. Outcomes measurements and statistical analysisMultivariable logistic regressions evaluated odds of high-grade (Gleason grade group ≥2) prostate cancer. Separate models were fit for family history definitions, including first- and second-degree prostate cancer and breast cancer family histories. Results and limitationsA first-degree prostate cancer family history was available for 15 799 men, with a more detailed family history for 4617 (median age 65 yr, both cohorts). Adjusted odds of high-grade prostate cancer were 1.77 times greater (95% confidence interval [CI] 1.57−2.00, p < 0.001, risk ratio [RR] = 1.40) with first-degree prostate cancer, 1.38 (95% CI 1.07−1.77, p = 0.011, RR = 1.22) for second-degree prostate cancer, and 1.30 (95% CI 1.01−1.67, p = 0.040, RR = 1.18) for first-degree breast cancer family histories. Interaction terms revealed that the effect of a family history did not differ based on prostate-specific antigen but differed based on age. This study is limited by missing data on race and prior negative biopsy. ConclusionsMen with indications for biopsy and a family history of prostate or breast cancer can be counseled that they have a moderately increased risk of high-grade prostate cancer, independent of other risk factors. Patient summaryIn a large international series of men selected for prostate biopsy, finding a high-grade prostate cancer was more likely in men with a family history of prostate or breast cancer.

A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer.

Simple SummaryMen of African origin have a 2–3 times greater chance of developing prostate cancer than those of European origin, and of patients that are diagnosed with the disease, men of African descent are 2 times more likely to die compared to white men. Men of African origin are still greatly underrepresented in genetic studies and clinical trials. This, unfortunately, means that new discoveries in cancer treatment are missing key information on the group with a greater chance of mortality. The objective of this study was to increase our knowledge of prostate cancer in men undergoing a prostate biopsy. We carried out RNA sequencing of biopsy specimens and examined racial differences in prostate gene expression. A gene expression signature was uncovered which separated the men based on their race. Furthermore, within men of African descent this signature separated men with the most severe clinical characteristics.An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.

MP30-14 5-ARI USAGE ASSOCIATED WITH MORE ADVANCED PROSTATE CANCER AT DIAGNOSIS

You have accessJournal of UrologyProstate Cancer: Detection & Screening III (MP30)1 Sep 2021MP30-14 5-ARI USAGE ASSOCIATED WITH MORE ADVANCED PROSTATE CANCER AT DIAGNOSIS Emily Roebuck, Wei Sha, Caroline Lu, Caroline Miller, Earle F Burgess, Claud M Grigg, Jason Zhu, Kris E Gaston, Stephen B Riggs, Justin T Matulay, Peter E Clark, and James T Kearns Emily RoebuckEmily Roebuck More articles by this author , Wei ShaWei Sha More articles by this author , Caroline LuCaroline Lu More articles by this author , Caroline MillerCaroline Miller More articles by this author , Earle F BurgessEarle F Burgess More articles by this author , Claud M GriggClaud M Grigg More articles by this author , Jason ZhuJason Zhu More articles by this author , Kris E GastonKris E Gaston More articles by this author , Stephen B RiggsStephen B Riggs More articles by this author , Justin T MatulayJustin T Matulay More articles by this author , Peter E ClarkPeter E Clark More articles by this author , and James T KearnsJames T Kearns More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002027.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer (PCa) risk is often modeled at referral based on Prostate Cancer Prevention Trial (PCPT) and Prostate Biopsy Collaborative Group (PBCG) risk calculators, which account for factors such as PSA, DRE, age, race, family history, and prior biopsy history. Prospective PCa chemoprevention trials noted an increased risk of high-grade prostate cancer among men using 5-ARIs, and subsequent retrospective data associates 5-ARI use with delayed diagnoses and worse cancer outcomes than non-users. The objective of this study was to assess clinical characteristics and treatment types between 5-ARI users versus non-users at prostate biopsy and PCa diagnosis. METHODS: Men undergoing prostate biopsy at our institution between January 2018–December 2021 were retrospectively reviewed for clinical and demographic data. Patients with previously diagnosed PCa were excluded. For categorical demographic or biopsy variables, Chi-square test was used to determine if there is a significant association between these variables and 5-ARI usage. For continuous demographic variables, quantile regression was used to compare the medians between 5-ARI users and non-users. False discovery rate (FDR) adjusted P value was used for multiple tests. RESULTS: Among 842 patients, 83 men were using 5-ARIs at time of biopsy (Table 1). Demographic characteristics including age, race, marital status, BMI, or family history were similar across the two cohorts. PSA was greater among 5-ARI users (p=.054). At PCa diagnosis, 5-ARI users tended to have higher clinical T stage (p<0.0001) and NCCN risk group stratification (p=.0119). Gleason Grade Group (p=0.372), prostate volume (p=.1838), DRE (p=.5849), and treatment type (p>.05 for all) were not statistically different between users and non-users. CONCLUSIONS: While not emphasized in common risk calculators, pre-diagnostic use of 5-ARI should be considered when deciding to biopsy. Our findings demonstrate 5-ARI usage associated with more advanced clinical T stage and higher NCCN risk though not Gleason Grade, suggesting that 5-ARI is a risk factor to consider at referral and highlighting the need to optimize diagnostic care for 5-ARI users. Source of Funding: No source of funding © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e505-e505 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Emily Roebuck More articles by this author Wei Sha More articles by this author Caroline Lu More articles by this author Caroline Miller More articles by this author Earle F Burgess More articles by this author Claud M Grigg More articles by this author Jason Zhu More articles by this author Kris E Gaston More articles by this author Stephen B Riggs More articles by this author Justin T Matulay More articles by this author Peter E Clark More articles by this author James T Kearns More articles by this author Expand All Advertisement Loading ...