You have accessJournal of UrologyProstate Cancer: Markers I (MP41)1 May 2024MP41-09 GENOMIC SIGNATURES ASSOCIATED WITH ADVERSE PATHOLOGIC FEATURES AT RADICAL PROSTATECTOMY AMONG ACTIVE SURVEILLANCE ELIGIBLE MEN Eric Victor Li, James Proudfoot, Nalin Kundu, Clayton Neill, Elai Davicioni, Edward Schaeffer, Hiten Patel, and Ashley Ross Eric Victor LiEric Victor Li , James ProudfootJames Proudfoot , Nalin KunduNalin Kundu , Clayton NeillClayton Neill , Elai DavicioniElai Davicioni , Edward SchaefferEdward Schaeffer , Hiten PatelHiten Patel , and Ashley RossAshley Ross View All Author Informationhttps://doi.org/10.1097/01.JU.0001008896.93851.5b.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) can be associated with significant rates of grade reclassification and progression to treatment. Genomic biomarkers offer opportunities to better identify durable AS candidates and elucidate a potential role for molecularly based therapies. We sought to define transcriptomic markers associated with adverse pathologic features among AS-eligible patients who underwent radical prostatectomy (RP). METHODS: We retrospectively identified AS-eligible [NCCN very low risk (VLR) to favorable intermediate risk (FIR) PCa] patients at our institution from 2/2012-3/2023 who underwent RP with Decipher testing (n=112). The primary outcome was adverse pathologic features (APF) at RP, defined as GG3-5, pT3b, or pN1 disease. Associations between APF and previously defined transcriptomic signatures derived from the Decipher GRID (PAM50, PSC, PTEN, and eleven prognostic signatures) were evaluated with Mann-Whitney U test, Fisher's exact test, and multivariable logistic regression. RESULTS: Of 112 men, 27% (30/112) had VLR or low risk PCa and 73.2% (82/112) had FIR PCa. At RP, 28% (31/112) had APF due to upgrading to GG3-5 (28/31, 90%) and 10% (3/31) due to upgrading and T3b disease. Men with APF had higher baseline PSA (6.42 ng/mL vs 4.9 ng/mL, p=0.02) and were less likely to have undergone an MRI fusion biopsy for diagnosis (71% vs 90%, p=0.02, Table 1). Seven of eleven previously characterized prognostic gene-based signatures were associated with APF on multivariable analysis (Figure 1). PTEN loss and increased activated tumoral CD4 activity were also significantly associated with APF. CONCLUSIONS: Despite similar clinical features at diagnosis, AS-eligible patients have significantly different outcomes and risk of APF due to molecular heterogeneity. The Decipher genomic classifier, PTEN loss, and activated CD4 activity at diagnosis are associated with APF among AS eligible patients. Clinical trials within AS populations should consider utility of genomic signatures in patient selection. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e676 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Eric Victor Li More articles by this author James Proudfoot More articles by this author Nalin Kundu More articles by this author Clayton Neill More articles by this author Elai Davicioni More articles by this author Edward Schaeffer More articles by this author Hiten Patel More articles by this author Ashley Ross More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract Introduction: PIRADS scoring with multiparametric-MRI (MRI) has a pooled 90% negative predictive value (NPV) allowing men to defer biopsy while enhancing Gleason Grade group 2-5 (GG2-5) prostate cancer (PCa) detection. PSA density (PSAD) ≥0.15ng/ml/cm3 has been shown to enhance NPV of the prostate MRI in non-Black men. We assessed the performance of the prostate MRI in Black vs. non-Black men by evaluating sensitivity and NPV, and identified a PSAD threshold providing ≥90% NPV in Black men. Methods: We prospectively recruited Black and non-Black men referred to outpatient urology clinics for abnormal PSA or prostate exam in three similar biomarker validation studies from 2017–23 before MRI-informed diagnostic transrectal or transperineal prostate biopsy. We combined this research cohort with a retrospective clinical cohort of clinically similar Black and non-Black men from one academic institution who also underwent prostate MRIs and MRI-informed biopsies for elevated PSA. Trained radiologists used PIRADS version 2.0 or 2.1 for scoring. Results: Following the combination of the research and clinical cohorts, 286 Black men and 965 non-Black men with PSA<15.0ng/ml were included in the analysis. PIRADS ≥3 had an NPV of 77.1% versus 87.6% and a sensitivity of 90.7% vs. 96.3% for GG2-5 PCa in Black versus non-Black men, respectively (both p<0.05). Using PSAD ≥0.09 for Black men with PIRADS 1-2 lesions increased sensitivity to 92.9%. For PIRADS 1-2, GG2-5 PCa frequency was 5.3% higher in Black versus non-Black men with PSAD<0.15, and 11.0% higher in Black versus non-Black men with PSAD≥0.15. For PIRADS=3, GG2-5 PCa frequency was 9.1% higher in Black men with PSAD<0.15 and 27.9% higher for PSAD≥0.15. For PIRADS=4, GG2-5 PCa frequency was 15.9% higher in Black men with PSAD<0.15, and 9.5% higher for PSAD≥0.15. Conclusion: The PIRADS ≥3 threshold has a lower NPV and sensitivity in Black men. A negative prostate MRI requires a PSAD ≥0.09 threshold for safe biopsy deferral in Black men to maintain a sensitivity ≥90%. Citation Format: Sarah Sandlow, Samuel Carbunaru MD, Zequn Sun PhD, Bernice Ofori MPH, Courtney M. P. Hollowell MD, Patricia Vidal MD, Eric Li MD, Edward M. Schaeffer MD, PhD, Peter Gann MD, ScD, Ashley Ross MD, PhD, Shilajit Kundu MD, Adam B. Murphy MD, MBA, MSCI. Lower negative predictive value of prostate MRI in Black men [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C014.

You have accessJournal of UrologyProstate Cancer: Staging II (PD45)1 May 2024PD45-12 FACTORS ASSOCIATED WITH PATHOLOGICAL RECLASSIFICATION OF LOW RISK PROSTATE CANCER Austin Y. Ho, Eric Li, Richard Bennett, Jonathan Aguiar, Sai Kumar, Clayton Neill, Zequn Sun, Edward Schaeffer, Hiten Patel, and Ashley Ross Austin Y. HoAustin Y. Ho , Eric LiEric Li , Richard BennettRichard Bennett , Jonathan AguiarJonathan Aguiar , Sai KumarSai Kumar , Clayton NeillClayton Neill , Zequn SunZequn Sun , Edward SchaefferEdward Schaeffer , Hiten PatelHiten Patel , and Ashley RossAshley Ross View All Author Informationhttps://doi.org/10.1097/01.JU.0001008792.09108.b4.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) is the preferred management for low grade prostate cancers. Predictors of reclassification to disease requiring treatment (best defined as presence of unfavorable intermediate risk cancer or greater) can inform men choosing AS of their likelihood to remain untreated over time. Here we analyze clinical and radiographical factors associated with clinically significant reclassification. METHODS: We retrospectively identified 629 men initially diagnosed with AUA low risk (LR) prostate cancer across our eleven-hospital system from January 2018 – September 2022. Definitions of reclassification were made either strictly on histopathology or as a combined definition including treatment. Univariable and multivariable logistic regression analysis was performed with statistical significance defined as a p<0.05. RESULTS: Among LR men, 93 (15%) opted for immediate treatment with radical prostatectomy (RP). Of those, 7 were found to have adverse pathology (AP) defined as Gleason Grade Group (GG) 3-5 disease. There were no significant differentiators among men with AP including NCCN very low risk (VLR) or LR risk, other metrics of disease volume, or MRI PIRADS score. When considering diagnostic features of AUA LR men opting for surveillance (median follow up time 485 days (307, 973)), reclassification to GG3-5 disease was only significantly associated with MRI PIRADS score (HR 6.6 (95% CI 1.5-27.9) for PIRADS 5 MRI prior to initial diagnosis) and logPSA density (PSAD) (HR 3.14 (95% CI, 1.14-8.65). Other tested risk factors including NCCN risk group, % positive cores, and maximum individual core positivity were only statistically significant when considering outcomes that included reclassification to GG2 disease or treatment for any cause. CONCLUSIONS: Among AUA low risk men undergoing surveillance, the presence of a PIRADS 5 lesion at diagnosis and higher PSAD were predictive of reclassification to GG3-5 disease. NCCN VLR or LR designations, and histological measurements of disease volume were only predictive of events when considering progression to treatment for any reason or when including questionably meaningful GG 2 pathological reclassifications. Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e972 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Austin Y. Ho More articles by this author Eric Li More articles by this author Richard Bennett More articles by this author Jonathan Aguiar More articles by this author Sai Kumar More articles by this author Clayton Neill More articles by this author Zequn Sun More articles by this author Edward Schaeffer More articles by this author Hiten Patel More articles by this author Ashley Ross More articles by this author Expand All Advertisement PDF downloadLoading ...

Introduction PSMA-based imaging is the preferred imaging modality recommended by NCCN guidelines for work-up of suspected recurrent or persistent prostate cancer after initial treatment with radical prostatectomy (RP) or prostate radiation and is increasingly being utilized in clinical practice. There is currently sparse data on the relative yield of PSMA PET/CT at low PSA values at biochemical recurrence. We evaluated our institutional PSMA PET/CT cohort of post-RP patients which includes 251 men with PSAs under 0.5ng/mL at the time of imaging, to identify clinical factors associated with scan positivity. Methods We retrospectively identified men treated initially with radical prostatectomy who underwent Gallium-68 or F-18 piflufolastat (DCFPyL) PSMA PET/CT for work-up of recurrence across our eleven hospital system from July 2021-March 2023. Patient characteristics, including demographic, baseline clinical, pathologic, and imaging variables, were obtained. PSMA positivity was determined based on radiology interpretation, and equivocal or likely benign lesions considered negative. Patients with history of systemic therapy or known metastatic disease (n=216), received focal therapy only (n=4), or had bladder outlet procedures only (n=3) were excluded. Clinical variables were compared with Wilcoxon Rank Test, Chi square, and Fishers’ exact test and subsequently with univariable and multivariable logistic regression. PSA was log transformed given non-normal distribution for logistic regression. Statistical significance was defined as p<0.05. Results Median PSA at time of PSMA PET/CT was 0.37 ng/mL (IQR 0.15, 1.29 ng/mL). 48.9% (210/429) of patients initially managed with RP were found to have PSMA positive finding suspicious for recurrence (Table 1). Rates of scan positivity among men with PSAs <0.5ng/mL and those <0.2ng/mL were 37% and 37% respectively.; Among patients with suspicious PSMA positive findings, 14% (29/210) had positivity within prostate bed only, 35% (74/210) had N1 disease, and 51% (107/210) had M1 disease. On multivariable analysis, age, PSA at PSMA scan, and RP Gleason Grade Group were significantly associated with PSMA positivity (Table 2). In a subset MVAs for men with PSAs under 0.5ng/mL at time of imaging, RP Gleason Grade group (p=0.02) and history of post-operative radiation (OR 2.12, 95% CI 1.13, 4, p=0.02) were associated with;scan positivity. Conclusions PET PSMA/CT for recurrence after RP identifies locoregional or metastatic disease in 49% of patients. Though men with higher PSAs (i.e. ≥ 1ng/ml) have the highest probability of harboring PSMA positive disease, roughly 40% of men with PSAs under 0.2ng/ml had positive imaging findings concerning for recurrence.; These men harbored higher grade disease at prostatectomy and were more likely to have received post-operative radiation.; Our findings suggest PET-PSMA imaging at low PSAs can be considered in selective individuals even at low PSA to inform salvage therapies.

Introduction Leuprolide is an injected GnRH agonist that has been the standard of care for patients receiving androgen deprivation therapy (ADT) for advanced prostate cancer. In December of 2020, relugolix was approved as the first oral GnRH antagonist which provided patients with an alternative form of ADT. Results of the phase III HERO study associated relugolix use with faster recovery of testosterone and potentially fewer major adverse cardiovascular events (MACE). In this study, we sought to determine the clinical characteristics and cardiovascular outcomes of patients with prostate cancer treated with leuprolide or relugolix at our multi-centered academic institution. Methods The Northwestern Electronic Data Warehouse was queried for men with an established diagnosis of prostate cancer for whom leuprolide was prescribed between January 2018-July 2022 or for whom relugolix was prescribed between December 2020-July 2022. Patients who were prescribed leuprolide were further stratified into a pre-relugolix era (January 2018-November 2020) and a post-relugolix era (December 2020-July 2022). Baseline clinicopathologic characteristics,;Charlson Comorbidity Index (CCI), and cardiac outcomes following initiation of ADT were collected. MACEs were defined as non-fatal myocardial infarction (MI), non-fatal stroke, and death from any cause. Concurrent ADT use was defined as prescription of another form of ADT (darolutamide, enzalutamide, apalutamide, abiraterone, docetaxel, cabazitaxel) during the same period. Clinical variables were compared with one-way ANOVA, t-test, Chi square and Fisher's exact test and statistical significance was defined as a p<0.05. Bonferroni correction was applied for the pairwise comparisons and statistical significance was defined as p<0.025. Results 403 men were prescribed leuprolide (n=225 in the pre-relugolix era, n=178 in the post-relugolix era) and 229 men were prescribed relugolix at our institution during the study period. Most patients (73%) had a history of at least one cardiovascular disease risk factor prior to initiation of therapy. Patients prescribed relugolix were overall younger, had fewer comorbidities, and were less likely to harbor metastatic disease (Tables 1,2). Following the initiation of ADT, 75 MACEs were observed. 44 occurred in the pre-relugolix leuprolide cohort, 15 occurred in the post-relugolix leuprolide cohort, and 16 occurred in the relugolix cohort. The respective incidences of major adverse cardiac events were 19.5%, 8.4%, and 7.0%. Death from any cause was the most common (n=52), followed by cerebral infarction (n=10), transient ischemic attacks (n=9), and acute MI (n=4). Of the deaths, 3, 0, and 3 were cardiac arrest or stroke for each cohort respectively. Conclusions Our findings revealed similar incidences of MACEs for patients prescribed leuprolide or relugolix in the same period, however, patients who were prescribed leuprolide in the pre-relugolix era experienced a significantly greater incidence of MACEs. The higher rates observed in this cohort may be linked to the increased duration of follow-up and cumulative exposure to therapy. Due to the retrospective nature of the analysis, there were also significant limitations in regard to follow-up time and sample size for evaluation of MACEs. Ultimately, our results show a possible preference for initiation of relugolix in a younger population undergoing therapy for defined duration where rapid testosterone recovery may be favored.

283 Background: PSMA-based imaging improves detection of metastatic disease for initial staging of men diagnosed with prostate cancer (PCa) with higher accuracy compared to conventional imaging. PSMA imaging is now being increasingly adopted for initial local and distant metastatic staging. We sought to determine the contribution of clinical and pathological factors associated with PSMA positive nodal or metastatic disease. Methods: We retrospectively identified 404 men diagnosed with PCa who underwent initial staging with Gallium-68 or F-18 piflufolastat (DCFPyL) PSMA PET/CT across our eleven-hospital system from July 2021-December 2022. Patient characteristics, including demographic, clinical, pathologic, and imaging variables were obtained. PSMA positivity representing a suspicious nodal or distant lesion was determined based on radiology reports, histopathology, and other imaging modalities, and equivocal or likely benign lesions were counted as negative. Patients with prior diagnosis (>6 months) of PCa (n=42) or incomplete clinical history (n=22) were excluded. Clinical variables were compared with Wilcoxon Rank Test, Chi square, and Fishers’ exact test as well as univariable and multivariable logistic regression. Number of risk factors for patients with unfavorable intermediate or very high risk disease was also examined. PSA was log transformed. Statistical significance was defined as p<0.05. Results: 103/340 patients (30.3%) had PSMA imaging findings concerning for nodal or distant metastatic disease. Patients with positive finding were less likely to be Black, and had higher PSA, biopsy Gleason Grade Group, and higher presumptive NCCN risk. Stratifying by pre-scan NCCN risk group, PSMA positivity was observed in no patients with favorable intermediate risk PCa (n=17), 9.8% (12/123) with unfavorable intermediate risk PCa, 29% (25/86) with high risk PCa, and 58% (66/114) with very high risk PCa. Stratifying by number of risk factors, there were significant differences in scan positivity comparing unfavorable intermediate risk disease with 1 vs ≥2 risk factors (4.2% vs 17%, p=0.03) and very high risk disease with 1 risk vs ≥2 risk factors (49% vs 72%, p=0.01). On multivariable analysis, NCCN classification stratified by risk factors was associated with PSMA positivity while Black race was inversely associated (OR 0.32, 95% CI 0.11, 0.82, p=0.03). Conclusions: Initial staging with PSMA PET/CT identified local regional or metastatic disease in 30% of PCa patients. A substantial proportion of unfavorable intermediate risk men were N1 or M1 based on PSMA positivity, particularly those with multiple unfavorable intermediate risk features. The clinical benefit for PSMA PET/CT in patients with favorable intermediate risk PCa is low. Limitations include retrospective design (including possible selection bias for patients with equivocal lesions on conventional imaging) and a limited number of black men in the cohort.

35 Background: PSMA PET is increasingly utilized for the evaluation of disease stage at biochemical recurrence. Here we evaluate the association of clinico-pathologic features with PSMA findings in biochemically recurrent patients after primary prostate radiation therapy (RT). Methods: We queried the Northwestern Medical System Electronic Data Warehouse between July 2021 and March 2023 to identify 122 men treated with primary RT for presumptive localized prostate cancer who subsequently underwent Gallium-68 or F-18 piflufolastat (DCFPyL) PSMA PET/CT for staging. Patient characteristics, including demographic, clinical, pathological, and imaging variables were obtained. PSMA positivity for suspicious nodal or metastatic disease was determined based on radiology interpretation, with equivocal or likely benign lesions considered as negative findings. Patients with incomplete clinical history (n=3) were excluded. Clinical variables were compared using a Wilcoxon rank-sum and Fisher’s exact tests. Regression analysis was performed to determine variables associated with PSMA positivity in biochemically recurrent patients. Statistical significance was determined if the p-value was less than 0.05. Results: Among the 119 men staged with PET PSMA after RT, median PSA was 3.18 (IQR 1.35, 5.55 ng/mL). 78% (93/119) were found to have suspicious PSMA positive disease. 39% had PSMA positivity in the prostate only (46/119), 6.7% had pelvic nodal disease (8/119), and 33% had extrapelvic disease (39/119). On univariable regression analysis, PSA at the time of PSMA was the only factor associated with PSMA positivity (OR 1.32 per 1 point increase, 95% CI 1.10, 1.67, p=0.01; Table). Higher PSAs at the time of scan were additionally associated with distant recurrence (73.3% of men with distant recurrence if scanned at PSA >10ng/mL versus 31.9% if scanned at PSA <4ng/mL p=0.029). 20% (9/46) of men with PSMA positivity within the prostate were biopsied identifying 78% (7/9) positivity, of which 67% (4/6) receiving treatment selected management with salvage treatments. Conclusions: Patients with prostate cancer initially treated with RT showed significant rates of PSMA positive disease even when scanned at low PSAs (including many below the nadir+2ng/mL definition). Evaluation at low PSAs favors the identification of localized disease only which can be cured by salvage therapy if confirmed by biopsy (i.e. prostatectomy, cryoablation, HIFU). [Table: see text]

e17001 Background: Computational analysis of digitized pathological images has been shown to have diagnostic and prognostic applications. Recent research suggests that molecular features, previously defined at the genomic level, might be additionally recognized. In prostate cancer, transcriptomic PAM50 molecular subtypes may correlate with patient response to systemic therapy. Here we investigate whether computational analysis of digital prostate biopsy slides can predict PAM50 category. Methods: Our study utilized digitized images of 704 prostate biopsy slides from 336 patients with prostate cancer at Northwestern Memorial Hospital with Decipher testing (Veracyte, Inc San Diego, CA). All slides analyzed contain carcinoma with the majority being primary Gleason pattern 3 (545 out of 704). Hematoxylin and eosin stained slides were scanned on a Leica GT450 scanner at 40x magnification. PAM50 subtypes were derived from the Decipher Genomic Resource Information Database (GRID). Data were split at the subject level using 80% for training, 10% for validation, and 10% for evaluation, facilitating model development and assessment. We devised a model comprising two decoupled parts: a multi-instance learning model that utilizes a multi-class attention mechanism to explore relevant class-specific information from slides, and a pre-trained network to extract high-dimensional semantic features from the tiles of WSIs. The model trained based on the WSIs of the training set to predict PAM50 subtypes (luminal A, luminal B, and basal). This attention-based training approach allowed the model to capture relevant patterns and information present in the WSIs. Following the training phase, the model was subsequently evaluated on the testing set. Results: Model AUC on the evaluation set was 0.78. Among evaluation set misclassifications, no luminal samples were misclassified as basal subtype. Conclusions: Our investigation provides preliminary results on the ability to predict RNA expression-based subtypes from prostate cancer biopsy histology. This approach may help to preserve tissue, minimize costs, and decrease turnaround time associated with molecular testing in prostate cancer while offering patients with prostate cancer opportunities for precision medicine.

ImportanceMagnetic resonance imaging (MRI)–based risk calculators can replace or augment traditional prostate cancer (PCa) risk prediction tools. However, few data are available comparing performance of different MRI-based risk calculators in external cohorts across different countries or screening paradigms.ObjectiveTo externally validate and compare MRI-based PCa risk calculators (Prospective Loyola University Multiparametric MRI [PLUM], UCLA [University of California, Los Angeles]-Cornell, Van Leeuwen, and Rotterdam Prostate Cancer Risk Calculator–MRI [RPCRC-MRI]) in cohorts from Europe and North America.Design, Setting, and ParticipantsThis multi-institutional, external validation diagnostic study of 3 unique cohorts was performed from January 1, 2015, to December 31, 2022. Two cohorts from Europe and North America used MRI before biopsy, while a third cohort used an advanced serum biomarker, the Prostate Health Index (PHI), before MRI or biopsy. Participants included adult men without a PCa diagnosis receiving MRI before prostate biopsy.InterventionsProstate MRI followed by prostate biopsy.Main Outcomes and MeasuresThe primary outcome was diagnosis of clinically significant PCa (grade group ≥2). Receiver operating characteristics for area under the curve (AUC) estimates, calibration plots, and decision curve analysis were evaluated.ResultsA total of 2181 patients across the 3 cohorts were included, with a median age of 65 (IQR, 58-70) years and a median prostate-specific antigen level of 5.92 (IQR, 4.32-8.94) ng/mL. All models had good diagnostic discrimination in the European cohort, with AUCs of 0.90 for the PLUM (95% CI, 0.86-0.93), UCLA-Cornell (95% CI, 0.86-0.93), Van Leeuwen (95% CI, 0.87-0.93), and RPCRC-MRI (95% CI, 0.86-0.93) models. All models had good discrimination in the North American cohort, with an AUC of 0.85 (95% CI, 0.80-0.89) for PLUM and AUCs of 0.83 for the UCLA-Cornell (95% CI, 0.80-0.88), Van Leeuwen (95% CI, 0.79-0.88), and RPCRC-MRI (95% CI, 0.78-0.87) models, with somewhat better calibration for the RPCRC-MRI and PLUM models. In the PHI cohort, all models were prone to underestimate clinically significant PCa risk, with best calibration and discrimination for the UCLA-Cornell (AUC, 0.83 [95% CI, 0.81-0.85]) model, followed by the PLUM model (AUC, 0.82 [95% CI, 0.80-0.84]). The Van Leeuwen model was poorly calibrated in all 3 cohorts. On decision curve analysis, all models provided similar net benefit in the European cohort, with higher benefit for the PLUM and RPCRC-MRI models at a threshold greater than 22% in the North American cohort. The UCLA-Cornell model demonstrated highest net benefit in the PHI cohort.Conclusions and RelevanceIn this external validation study of patients receiving MRI and prostate biopsy, the results support the use of the PLUM or RPCRC-MRI models in MRI-based screening pathways regardless of European or North American setting. However, tools specific to screening pathways incorporating advanced biomarkers as reflex tests are needed due to underprediction.

CONCLUSIONS: The majority of patients who were prescribed relugolix had at least 1 cardiac comorbidity, and the subsequent rate of major adverse cardiac events was similar to the HERO registrational trial (4.8% vs 3.6%). Our fi ndings illustrate a real-world experience of patients initiating therapy with relugolix, comorbidities present at initia- tion, providers managing the drug, and cardiovascular and survival outcomes following its use

You have accessJournal of UrologyCME1 Apr 2023MP44-11 DETECTION OF SUBSEQUENT CLINICALLY SIGNIFICANT PROSTATE CANCER FOLLOWING INITIAL DECISION TO FORGO BIOPSY IN THE MULTIPARAMETRIC MRI ERA Eric Li, Anna Busza, Mohammad Siddiqui, Jonathan Aguiar, Parth Shah, Ashorne Mahenthiran, Jasmine Lin, Moataz Soliman, Sai Kumar, Mary Kate Keeter, Clayton Neill, Xinlei Mi, Quan Mai, Edward Schaeffer, Hiten Patel, and Ashley Ross Eric LiEric Li More articles by this author , Anna BuszaAnna Busza More articles by this author , Mohammad SiddiquiMohammad Siddiqui More articles by this author , Jonathan AguiarJonathan Aguiar More articles by this author , Parth ShahParth Shah More articles by this author , Ashorne MahenthiranAshorne Mahenthiran More articles by this author , Jasmine LinJasmine Lin More articles by this author , Moataz SolimanMoataz Soliman More articles by this author , Sai KumarSai Kumar More articles by this author , Mary Kate KeeterMary Kate Keeter More articles by this author , Clayton NeillClayton Neill More articles by this author , Xinlei MiXinlei Mi More articles by this author , Quan MaiQuan Mai More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , Hiten PatelHiten Patel More articles by this author , and Ashley RossAshley Ross More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003290.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Advanced biomarker tests and multiparametric prostate MRI (mpMRI) have improved risk stratification for detection of clinically significant prostate cancer (csPCa, ISUP Grade Group 2+). However, subsequent testing and detection of csPCa among men forgoing initial biopsy has not been well described. Here we characterize the subsequent detection of csPCa in patients who had an initial MRI without biopsy. METHODS: We retrospectively identified biopsy-naïve men presenting with elevated PSA 2-20 ng/mL from March 2018 to June 2021 who received evaluation with mpMRI before biopsy consideration. Initial and follow-up clinicopathologic data including PSA, Prostate Health Index (PHI), mpMRI, and pathology reports were obtained. T-test, Chi-squared, Wilcoxon rank sum test, and multivariable logistic regression were performed. RESULTS: 1494 men underwent mpMRI for initial evaluation, after which 463 (31%) did not pursue biopsy. On multivariable analysis, PSA density (PSAD) <0.1, PHI <55, and PIRADS 1-2 on mpMRI were significant predictors of omitting initial prostate biopsy. Of the men who did not initially receive biopsy, 353 men had minimum 6 months follow-up with median follow-up of 1.8 years. 15% (53/353) underwent repeat mpMRI. Overall, 2% of men (n=7) who originally omitted biopsy with follow-up were subsequently diagnosed with csPCa, six on subsequent prostate biopsy and one with incidental csPCa after holmium enucleation of the prostate (HoLEP). All patients diagnosed with csPCa had PIRADS 4 or 5 on repeat MRI. CONCLUSIONS: The subsequent detection rate of csPCa among patients not initially biopsied after mpMRI is low at 2%. Of the patients followed by serum biomarkers (i.e. PSA) with for cause MRIs, only the patients who developed PIRADS 4 or 5 lesions were found to have csPCa. Our institutional experience suggests that decisions to omit biopsy after MRI are often safe; additionally, if there is clinical suspicion leading to a repeat MRI, biopsy can again be omitted for mpMRIs scored as PIRADS 1-3. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e615 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eric Li More articles by this author Anna Busza More articles by this author Mohammad Siddiqui More articles by this author Jonathan Aguiar More articles by this author Parth Shah More articles by this author Ashorne Mahenthiran More articles by this author Jasmine Lin More articles by this author Moataz Soliman More articles by this author Sai Kumar More articles by this author Mary Kate Keeter More articles by this author Clayton Neill More articles by this author Xinlei Mi More articles by this author Quan Mai More articles by this author Edward Schaeffer More articles by this author Hiten Patel More articles by this author Ashley Ross More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 May 2022PD27-02 IS CAPSULAR ABUTMENT ON MRI A PREDICTOR OF EXTRAPROSTATIC EXTENSION (EPE) ON RADICAL PROSTATECTOMY? Mohammad Siddiqui, Jonathan Aguiar, Eric Li, Brandon Ansbro, Moataz Soliman, Mary-Kate Keeter, Quan Mai, Edward Schaeffer, and Ashley Ross Mohammad SiddiquiMohammad Siddiqui More articles by this author , Jonathan AguiarJonathan Aguiar More articles by this author , Eric LiEric Li More articles by this author , Brandon AnsbroBrandon Ansbro More articles by this author , Moataz SolimanMoataz Soliman More articles by this author , Mary-Kate KeeterMary-Kate Keeter More articles by this author , Quan MaiQuan Mai More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , and Ashley RossAshley Ross More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002575.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Extraprostatic extension (EPE) on radical prostatectomy (RP) pathology is an established prognostic indicator of recurrence and metastasis. Furthermore, suspicion of EPE guides neurovascular preservation during surgery. Here we investigate whether capsular ‘abutment’ on pre-operative mpMRI of the prostate predicts pathological findings. METHODS: We queried our prospectively collected institutional database from 2018 for all men undergoing radical prostatectomy (RP) who had undergone preoperative prostate MRI. Statistics were performed using t-test, chi-squared analysis, and logistical regressions with significance defined as p <0.05. RESULTS: 539 men underwent RP since March 2018. 307 (56%) men had pre-operative MRI. 163 (53.1%) had abutment of the capsule on MRI. For men with capsular abutment, 75 (46.25%) had EPE at prostatectomy (matched laterality in 42 (56%), on the contralateral side from their MRI lesion in 33 (44%)). 65/144 (45.1%) of men without capsular abutment on MRI had EPE on RP pathology. Men with ipsilateral EPE to their MRI lesions with capsular abutment were more likely to have a higher total prostate health index (PHI) (mean 64.20 vs. 50.95, p-value 0.024), and higher Gleason Grade Group (GG) lesion on diagnostic biopsy (p-value 0.001). Independent predictors of having ipsilateral EPE on multivariable logistic regression analysis include GG3 (OR 3.65, 95% CI 1.2-11.1) and GG4 (OR 4.7, 95%CI 1.2-18.8) on primary biopsy. On multivariable logistic regression analysis, MRI PIRADS scores were not predictive of either presence of ‘any’ EPE or ipsilateral EPE on final RP pathology. CONCLUSIONS: In our series, the presence or absence of “capsular abutment” alone read on MRI was a poor indicator of extra-prostatic extension on final pathology. Source of Funding: UROLOGY CARE FOUNDATION RESIDENCY RESEARCH AWARD © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e493 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohammad Siddiqui More articles by this author Jonathan Aguiar More articles by this author Eric Li More articles by this author Brandon Ansbro More articles by this author Moataz Soliman More articles by this author Mary-Kate Keeter More articles by this author Quan Mai More articles by this author Edward Schaeffer More articles by this author Ashley Ross More articles by this author Expand All Advertisement PDF DownloadLoading ...

You have accessJournal of UrologyCME1 May 2022PD17-05 CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH PIRADS 5 LESIONS AND NEGATIVE BIOPSIES Eric Li, Mohammad Siddiqui, Jonathan Aguiar, Brandon Ansbro, Parth Shah, Moataz Soliman, Jordan Rich, Jasmine Lin, Johan Alfaro Carballo, Mary Kate Keeter, Quan Mai, Edward Schaeffer, and Ashley Ross Eric LiEric Li More articles by this author , Mohammad SiddiquiMohammad Siddiqui More articles by this author , Jonathan AguiarJonathan Aguiar More articles by this author , Brandon AnsbroBrandon Ansbro More articles by this author , Parth ShahParth Shah More articles by this author , Moataz SolimanMoataz Soliman More articles by this author , Jordan RichJordan Rich More articles by this author , Jasmine LinJasmine Lin More articles by this author , Johan Alfaro CarballoJohan Alfaro Carballo More articles by this author , Mary Kate KeeterMary Kate Keeter More articles by this author , Quan MaiQuan Mai More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , and Ashley RossAshley Ross More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002555.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Best evidence supports use of mpMRI prior to initial diagnosis of prostate cancer. PIRADS 5 lesions typically have a 80-90% concordance with diagnosis of clinically significant disease. Here we investigate the characteristics and outcomes of patients with PIRADS 5 lesions and subsequent negative biopsies. METHODS: We queried our institutional database for men without an established diagnosis of prostate cancer for whom MRI targeted biopsy was performed after demonstration of a PIRADS 5 lesion from March 2018-present. T test, chi-squared test, and logistic regression were performed. RESULTS: 2,206 men underwent MRI for suspicion of prostate cancer, with PIRADS 5 lesions detected in 268 patients. 257 of these men underwent prostate biopsy (13 with transperineal biopsy) with a positivity rate of 93.8%. Men with PIRADS 5 lesions and negative biopsies (n=16) were more likely to be African American (25% vs 13.3%, p<0.001), younger (61.4 vs 66.3, p=0.03), have larger prostates (80.3 g vs 48.4 g, p<0.001), and have lower prostate health index (PHI, 44.3 vs. 78.2, p=0.04). There was no significant difference in anterior lesions, prostate inflammation, PSA, or PSA density. Of men with negative prostate biopsies, 1 patient was subsequently diagnosed with prostate cancer, and 2 patients had bladder outlet procedures with negative pathology. 2 patients with negative biopsies previously received BCG for non-muscle invasive bladder cancer and were subsequently found to have inflammation on prostate biopsy. CONCLUSIONS: Men with PIRADS 5 lesions and negative prostate biopsies tend to be African American, younger, have larger prostates, and have lower PHI compared to patients with positive prostate biopsies. Additional investigation is needed to determine lesion location is a risk factor for undersampling that may benefit from transperineal prostate biopsy, as well as the role of inflammation in determining how to follow these patients. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e337 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eric Li More articles by this author Mohammad Siddiqui More articles by this author Jonathan Aguiar More articles by this author Brandon Ansbro More articles by this author Parth Shah More articles by this author Moataz Soliman More articles by this author Jordan Rich More articles by this author Jasmine Lin More articles by this author Johan Alfaro Carballo More articles by this author Mary Kate Keeter More articles by this author Quan Mai More articles by this author Edward Schaeffer More articles by this author Ashley Ross More articles by this author Expand All Advertisement PDF DownloadLoading ...

You have accessJournal of UrologyCME1 May 2022PD57-06 FACTORS PREDICTING CLINICALLY SIGNIFICANT PROSTATE CANCER IN PIRADS 3 LESIONS Jasmine Lin, Mohammad Rashid Siddiqui, Eric Li, Jonathan Aguiar, Brandon Ansbro, Moataz Soliman, Jordan Rich, Johan Alfaro, Mary Kate Keeter, Edward Schaeffer, and Ashley Ross Jasmine LinJasmine Lin More articles by this author , Mohammad Rashid SiddiquiMohammad Rashid Siddiqui More articles by this author , Eric LiEric Li More articles by this author , Jonathan AguiarJonathan Aguiar More articles by this author , Brandon AnsbroBrandon Ansbro More articles by this author , Moataz SolimanMoataz Soliman More articles by this author , Jordan RichJordan Rich More articles by this author , Johan AlfaroJohan Alfaro More articles by this author , Mary Kate KeeterMary Kate Keeter More articles by this author , Edward SchaefferEdward Schaeffer More articles by this author , and Ashley RossAshley Ross More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002637.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Though PIRADS 3 lesions are commonly biopsied, the majority are benign. Here, we sought to investigate factors that may help better risk stratify the PIRADS-3 lesions and predict the presence of clinically significant cancer (defined as Gleason Grade Group (GG) ≥ 2). METHODS: We queried the electronic medical record for patients diagnosed with PIRADS 3 lesions beginning in March 2018 with the focus on patients with total PSA 2-20ng/mL. We compared the clinical characteristics such as Age, African American race, PSA, prostate health index (PHI), and PSA Density (PSAD) of patients with and without clinically significant prostate cancer on biopsy (Table 1). Statistics were performed using t-test, chi-squared analysis, and logistical regressions with significance defined as p<0.05. RESULTS: From March 2018 to present, 3553 men presented to urology at Northwestern Memorial Hospital with suspicion of prostate cancer with 1640 (46%) undergoing prostate MRI. 362 (22%) of men were identified to have the PIRADS 3 lesion as their highest PIRADS lesion. Subsequently, 280 (77%) men underwent prostate needle biopsy with clinically significant cancer detected in 57 (20%) of patients (171 (61%) were negative, while GG1 was found in 51 (18%) of patients). A significant difference was noted between the two groups for PHI (p-value 0.0001) and PSAD (p-value 0.001). Significant predictors of finding clinically significant prostate cancer on biopsy on multivariable analysis included PSAD >0.15 (OR 3.7, 95% CI 0.86-11.60) and PHI ≥ 55(OR 7.5, 95% CI 1.3-41.5). CONCLUSIONS: Consistent with literature, majority of PIRADS 3 lesions are benign in our series, but these lesions can be further risk stratified based on serum biomarker of PHI and PSAD. Roughly 90% of biopsies for men with PIRADS 3 lesions and PHI <36 or PSAD <0.15 failed to demonstrate clinically significant prostate cancer and consideration for biopsy avoidance should be made in these men. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e962 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jasmine Lin More articles by this author Mohammad Rashid Siddiqui More articles by this author Eric Li More articles by this author Jonathan Aguiar More articles by this author Brandon Ansbro More articles by this author Moataz Soliman More articles by this author Jordan Rich More articles by this author Johan Alfaro More articles by this author Mary Kate Keeter More articles by this author Edward Schaeffer More articles by this author Ashley Ross More articles by this author Expand All Advertisement PDF downloadLoading ...