To evaluate whether a two-step, ‘stage-gated’ reporting approach could improve the positive predictive value (PPV) of biparametric (bp)MRI for prostate cancer (PCa) screening compared to conventional Likert/PI-RADS scoring. This retrospective secondary analysis utilised data from IP1-PROSTAGRAM—a prospective, population-based study of men aged 50–69 years who underwent PCa screening with bpMRI, ultrasound and prostate-specific antigen (PSA) testing between October 2018 and May 2019 at two centres (NCT03702439). MRI scans from IP1-PROSTAGRAM were retrospectively evaluated using the ‘stage-gated’ approach: three radiologists independently reviewed limited MRI sequences (axial T2-weighted and b1500 diffusion-weighted images) and classified scans as positive or negative; if positive, the remaining bpMRI images were reviewed and a hypothetical “decision-to-biopsy” made. The PPV of ‘stage-gated’ reading was compared to PI-RADS and Likert scores ≥ 4 from the original IP1-PROSTAGRAM bpMRI reports. The reference standard was IP1-PROSTAGRAM biopsy results with grade group (GG) ≥ 2 cancer considered significant. Of 408 participants (median age 57 years [IQR 53, 61]), 405 had MRI scans available for secondary analysis. The prevalence of GG ≥ 2 cancer was 4

BACKGROUND AND OBJECTIVE:The quality and reporting of prostate magnetic resonance imaging (MRI) are operator dependent, leading to variations in estimates such as positive predictive value across sites. This impacts patient counseling, risk modeling, and risk calculators. This study assessed variation in Prostate Imaging Reporting and Data System (PI-RADS) score classification and subsequent probability of grade group (GG) ≥2 + prostate cancer. METHODS:Data from the Prostate Biopsy Collaborative Group, including multiple sites in North America, Europe, and Asia Pacific, were analyzed. Patients underwent multiparametric MRI (mpMRI) of the prostate followed by prostate biopsy during the years 2010-2023. Only those with MRI-targeted biopsy and PI-RADS score ≥3 were included. The risk of being assigned PI-RADS 4 or 5 and risk of GG ≥2 disease for these scores were estimated using logistic regression. KEY FINDINGS AND LIMITATIONS:The cohort included 7325 biopsies from 7320 unique patients from 13 sites. A two-fold variation in the probability of PI-RADS 4 or 5 assignment across sites persisted even after adjustment for patient risk (heterogeneity p < 0.001 for both). There were significant differences in the absolute risk of GG ≥2 disease for PI-RADS 4 and 5 (heterogeneity p < 0.001 for both), varying between 23% and 68% and between 49% and 87%, respectively. The use of prostate biopsy as a reference standard has limitations but reflects typical usage of mpMRI in clinical practice. CONCLUSIONS AND CLINICAL IMPLICATIONS:The probability of being assigned PI-RADS 4 or 5 and subsequent detection of GG ≥2 disease varies widely between institutions. This impacts counseling, risk stratification, and clinical practice, necessitating better standardization in the performance and interpretation of mpMRI.

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy II (PD39)1 May 2024PD39-01 THE SUITABILITY OF HEMI-ABLATION FOR PATIENTS DIAGNOSED WITH LOCALISED PROSTATE CANCER FOLLOWING MULTIPARAMETRIC MRI TARGETED AND NON-TARGETED TRANSPERINEAL PROSTATE BIOPSY Deepika Reddy, David Eldred-Evans, Mathias Winkler, Taimur Shah, and Hashim U. Ahmed Deepika ReddyDeepika Reddy , David Eldred-EvansDavid Eldred-Evans , Mathias WinklerMathias Winkler , Taimur ShahTaimur Shah , and Hashim U. AhmedHashim U. Ahmed View All Author Informationhttps://doi.org/10.1097/01.JU.0001008924.16121.42.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Evidence reporting comparable medium-term outcomes following focal therapy versus radical treatment modalities for localised prostate cancer is growing. Within the UK and Europe, despite being permitted if outcomes are prospectively collected, focal cryotherapy and High Intensity Focussed Ultrasound (HIFU) is only available in select centres. It is possible that not all patients suitable for focal therapy are referred for consideration for such treatment at select tertiary centres as the proportion of potentially suitable patients once diagnosed with localised prostate cancer is not widely understood. We determined how many patients diagnosed with localised prostate cancer following MRI and transperineal prostate biopsy in multiple prospective observational studies could be suitable for hemi-ablation. METHODS: Patients recruited into PICTURE trial, PROMIS trial, and RAPID pilot pathway were evaluated. Suitability was determined according to the Delphi Consensus criteria: PSA ≤20ng/ml, ≤rT3aN0, Gleason Grade Group (GGG) ≤3, if highest(GGG) was 1 then cancer length must be ≥6mm, and treatment pattern allowed up to unilateral hemi-ablation and spared at least 1 neurovascular bundle. Primary outcome allowed up to 5mm GGG1 to be untreated, secondary outcome allowed up to 5mm GGG1±1 core of 3+4 to remain untreated. Each study obtained local or external Research and Ethics approval. RESULTS: 200/330(61%) of patients recruited into PICTURE were diagnosed with ≤rT3aN0 prostate cancer and PSA ≤20ng/ml. 146/200(73%) had either GGG 2 or 3, or 1 with MCCL≥6mm, 3 had GGG>3, 51 had GGG1<6mm. 96/200(48%) patients had disease suitable for hemi-ablation, 63 would have untreated GGG1<6MM disease. When allowing for 5mm GG1±1 core of 3+4 to remain untreated 114/200(57%) were suitable for hemi-ablation.Within PROMIS 406/740(55%) patients had ≤rT3aN0 prostate cancer and PSA≤20ng/ml. 277/406(68%) had either GGG 2 or 3, or 1 with MCCL≥6mm, 24 had GGG>3, 91 had GGG1<6mm. 159/277(57%) patients had disease suitable for hemi-ablation, 81 would have untreated GGG1<6mm disease. When allowing for 5mm GG1±1 core of 3+4 to remain untreated 177/277(64%) were suitable for hemi-ablation. 612/2372(26%) of patients in RAPID were diagnosed with ≤rT3aN0 disease and PSA≤20ng/ml. 423/612(46%) had either GGG 2 or 3, or 1 with MCCL≥6mm, 83/612 had GGG>3, 103/612 had GGG1<6mm. 309/612(50%) had disease suitable for hemi-ablation, 41 of whom would have untreated GGG1<6mm disease. When allowing for 5mm GG1±1 core of 3+4 to remain untreated 313/612(51%) were suitable for hemi-ablation. CONCLUSIONS: Independent of varying incidence of prostate cancer within the cohorts evaluated, once diagnosed with localised disease between 5 and 6 patients out of 10 could be considered suitable for focal treatment, thus patients should be counselled and referred accordingly. Source of Funding: Nil © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e813 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Deepika Reddy More articles by this author David Eldred-Evans More articles by this author Mathias Winkler More articles by this author Taimur Shah More articles by this author Hashim U. Ahmed More articles by this author Expand All Advertisement PDF downloadLoading ...

Background Magnetic resonance imaging (MRI) of the prostate is a new, more accurate, non-invasive test for prostate cancer diagnosis. Aim To understand the acceptability of MRI for patients and GPs for prostate cancer diagnosis. Design and setting Qualitative study of men who had undergone a prostate MRI for possible prostate cancer, and GPs who had referred at least one man for possible prostate cancer in the previous 12 months in West London and Devon. Method Semi-structured interviews, conducted in person or via telephone, were audio-recorded and transcribed verbatim. Deductive thematic analysis was undertaken using Sekhon’s Theoretical Framework of Acceptability, retrospectively for patients and prospectively for GPs. Results Twenty-two men (12 from Devon, age range 47–80 years), two patients’ partners, and 10 GPs (6 female, age range 36–55 years) were interviewed. Prostate MRI was broadly acceptable for most patient participants, and they reported that it was not a significant undertaking to complete the scan. GPs were more varied in their views on prostate MRI, with a broad spectrum of knowledge and understanding of prostate MRI. Some GPs expressed concerns about additional clinical responsibility and local availability of MRI if direct access to prostate MRI in primary care were to be introduced. Conclusion Prostate MRI appears to be acceptable to patients. Some differences were found between patients in London and Devon, mainly around burden of testing and opportunity costs. Further exploration of GPs’ knowledge and understanding of prostate MRI could inform future initiatives to widen access to diagnostic testing in primary care.

You have accessJournal of UrologyProstate Cancer: Detection & Screening II (PD19)1 May 2024PD19-07 VARIATION IN THE POSITIVE PREDICTIVE VALUE OF PROSTATE MRI: DATA FROM THE PROSTATE BIOPSY COLLABORATIVE GROUP Sunny Nalavenkata, Emily Vertosick, Alberto Briganti, Hashim Ahmed, David Eldred-Evans, Kathie Wong, Stephen Gordon, Christian Gratzke, Michael Liss, Kim Moretti, Peter Ka-Fung Chiu, Michael Müntener, John Yaxley, Cedric Poyet, Matthias Jahnen, Daniel Margolis, Manish Patel, Behfar Ehdaie, and Andrew Vickers Sunny NalavenkataSunny Nalavenkata , Emily VertosickEmily Vertosick , Alberto BrigantiAlberto Briganti , Hashim AhmedHashim Ahmed , David Eldred-EvansDavid Eldred-Evans , Kathie WongKathie Wong , Stephen GordonStephen Gordon , Christian GratzkeChristian Gratzke , Michael LissMichael Liss , Kim MorettiKim Moretti , Peter Ka-Fung ChiuPeter Ka-Fung Chiu , Michael MüntenerMichael Müntener , John YaxleyJohn Yaxley , Cedric PoyetCedric Poyet , Matthias JahnenMatthias Jahnen , Daniel MargolisDaniel Margolis , Manish PatelManish Patel , Behfar EhdaieBehfar Ehdaie , and Andrew VickersAndrew Vickers View All Author Informationhttps://doi.org/10.1097/01.JU.0001009448.41537.64.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The diagnostic test characteristics of mpMRI, such as positive predictive value (PPV), are commonly given as single estimates. However, both mpMRI quality and reporting of the resulting images are operator dependent, suggesting that estimates such as PPV might vary between sites. This has implications in patient counseling, risk modeling and use of risk calculators. We used data from the Prostate Biopsy Collaborative Group to assess variation in the probability of being assigned different PIRADS scores and the probability of high grade cancer for a given PIRADS (PPV). METHODS: Data was collected from multiple international sites (North America, Europe, and Asia-Pacific) for patients undergoing mpMRI followed by prostate biopsy. Patients were included in this analysis if they were reported to have had an MRI-targeted biopsy and had a PIRADS score 3+. Data was analyzed to compare patient demographics, clinical practice and the variation in clinical practice. Risk of being assigned PIRADS 4 or 5, and risk of high grade disease for PIRADS 4 and 5, was estimated by logistic regression with adjustment for age, race, PSA, prostate volume, DRE result, family history and prior negative biopsy. RESULTS: The cohort includes 8147 patients from 12 participating sites. After adjustment for patient risk, we found greater than 2-fold variation in the probability of being called PIRADS 4 or 5 across sites (heterogeneity p<0.001 for both). The relative risk of high-grade cancer comparing PIRADS 4 vs 3 or 5 vs 3 did not differ across institutions (meta-analytic odds ratio 3.39, 95% CI 2.84 to 4.04, heterogeneity p=0.6 and 9.78, 95% CI 7.87 to 12.1, heterogeneity p=0.7). However, there were very large differences in absolute risk of high grade disease (that is, PPV) for both PIRADS 4 and 5 (heterogeneity p<0.001 for both). The heterogeneity between both rates of PIRADS 4 and 5 and risk of high grade disease on PIRADS 4 and 5 are presented in the Figure 1. CONCLUSIONS: The probability that a given patient would be called PIRADS 4 or 5, and the resultant probability of having high-grade disease (PPV), varies enormously between different institutions. This has immediate implications for current MRI based nomograms. Better practice standardization is urgently required for mpMRI performance and subsequent radiology interpretation. Download PPT Source of Funding: NIH Grant - 5R01CA179115-05 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e442 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Sunny Nalavenkata More articles by this author Emily Vertosick More articles by this author Alberto Briganti More articles by this author Hashim Ahmed More articles by this author David Eldred-Evans More articles by this author Kathie Wong More articles by this author Stephen Gordon More articles by this author Christian Gratzke More articles by this author Michael Liss More articles by this author Kim Moretti More articles by this author Peter Ka-Fung Chiu More articles by this author Michael Müntener More articles by this author John Yaxley More articles by this author Cedric Poyet More articles by this author Matthias Jahnen More articles by this author Daniel Margolis More articles by this author Manish Patel More articles by this author Behfar Ehdaie More articles by this author Andrew Vickers More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 Apr 2023MP73-11 MEDIUM TERM OUTCOMES FOLLOWING PRIMARY FOCAL CRYOTHERAPY FOR LOCALISED PROSTATE CANCER IN 323 PATIENTS, A MULTI-INSTITUTIONAL OBSERVATIONAL STUDY OVER 10 YEARS Deepika Reddy, Max Peters, Marieke Van Son, Mariana Bertoncelli Tanaka, Philipp Huber, Derek Lomas, Arnas Rakauskas, Saiful Miah, David Eldred-Evans, Emma Cullen, Tim Dudderidge, Stuart McCracken, Damian Greene, Raj Nigam, Neil McCartan, Massimo Valerio, Clement Orczyk, Jaspal Virdi, Manit Arya, Taimur Shah, and Hashim Ahmed Deepika ReddyDeepika Reddy More articles by this author , Max PetersMax Peters More articles by this author , Marieke Van SonMarieke Van Son More articles by this author , Mariana Bertoncelli TanakaMariana Bertoncelli Tanaka More articles by this author , Philipp HuberPhilipp Huber More articles by this author , Derek LomasDerek Lomas More articles by this author , Arnas RakauskasArnas Rakauskas More articles by this author , Saiful MiahSaiful Miah More articles by this author , David Eldred-EvansDavid Eldred-Evans More articles by this author , Emma CullenEmma Cullen More articles by this author , Tim DudderidgeTim Dudderidge More articles by this author , Stuart McCrackenStuart McCracken More articles by this author , Damian GreeneDamian Greene More articles by this author , Raj NigamRaj Nigam More articles by this author , Neil McCartanNeil McCartan More articles by this author , Massimo ValerioMassimo Valerio More articles by this author , Clement OrczykClement Orczyk More articles by this author , Jaspal VirdiJaspal Virdi More articles by this author , Manit AryaManit Arya More articles by this author , Taimur ShahTaimur Shah More articles by this author , and Hashim AhmedHashim Ahmed More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003341.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail WITHDRAWN © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1039 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Deepika Reddy More articles by this author Max Peters More articles by this author Marieke Van Son More articles by this author Mariana Bertoncelli Tanaka More articles by this author Philipp Huber More articles by this author Derek Lomas More articles by this author Arnas Rakauskas More articles by this author Saiful Miah More articles by this author David Eldred-Evans More articles by this author Emma Cullen More articles by this author Tim Dudderidge More articles by this author Stuart McCracken More articles by this author Damian Greene More articles by this author Raj Nigam More articles by this author Neil McCartan More articles by this author Massimo Valerio More articles by this author Clement Orczyk More articles by this author Jaspal Virdi More articles by this author Manit Arya More articles by this author Taimur Shah More articles by this author Hashim Ahmed More articles by this author Expand All Advertisement PDF downloadLoading ...

Approaches and techniques used for diagnostic prostate biopsy have undergone considerable evolution over the past few decades: from the original finger-guided techniques to the latest MRI-directed strategies, from aspiration cytology to tissue core sampling, and from transrectal to transperineal approaches. In particular, increased adoption of transperineal biopsy approaches have led to reduced infectious complications and improved antibiotic stewardship. Furthermore, as image fusion has become integral, these novel techniques could be incorporated into prostate biopsy methods in the future, enabling 3D-ultrasonography fusion reconstruction, molecular targeting based on PET imaging and autonomous robotic-assisted biopsy.

OBJECTIVEThe IP1-PROSTAGRAM study highlighted the potential of short biparametric "Prostagram" magnetic resonance imaging (bpMRI) scanning in screening for prostate cancer. We aimed to compare biopsy recommendation rates and accuracy of PI-RADSv2 with the Likert scale for detection of clinically significant and insignificant prostate cancer in men screened within IP1-PROSTAGRAM.PATIENTS AND METHODSMen aged 50-69 years were screened with Prostagram MRI. Scans were prospectively reported using both PI-RADSv2 (excluding dynamic contrast-enhanced sequence score) and 5-point Likert scores by expert uro-radiologists. Systematic and targeted transperineal biopsy was recommended if the scan was scored ≥3, based on either reporting system. The proportion of patients recommended for biopsy and detection rates for grade groups (GG) 1 and ≥2 were compared. Receiver operating characteristic (ROC) analysis was performed to compare performance.RESULTS406 men underwent Prostagram MRI. Median age and PSA were 57 years (IQR 53-61) and 0.91 ng/mL (0.56-1.74), respectively. At MRI score ≥3, more patients were recommended for biopsy based on Likert criteria (94/406, 23% [95% CI 19.2-27.6%]) compared to PI-RADSv2 (72/406, 18% [14.2-21.9%]; p=0.03). For scores ≥4, PI-RADSv2 and Likert scales led to 43/406 (11%, 7.9%-14.1%) and 35/406 (9%, 6.2-11.9%) men recommended for biopsy (p=0.40). For GG≥2 detection, PIRADSv2 and Likert detected 22% (11.4-30.8%, 14/72) and 16% (9.5-25.3%, 15/94), respectively (p=0.56). For GG1 cancers detection these were 11% (4.3-19.6%, 7/72) vs 11% (4.7-17.8%, 9/94) (p=1.00). The accuracy of PI-RADS and Likert scale was similar (AUROC 0.64 vs 0.65, p=0.95).CONCLUSIONSIn reporting non-contrast-enhanced Prostagram MRI in a screening population, the PI-RADSv2 and Likert scoring systems were equally accurate; however, Likert scale use led to a more men undergoing biopsy without a subsequent increase in significant cancer detection rates. To improve reporting of Prostagram MRI, either the PI-RADS or a modified Likert scale or a standalone scoring system should be developed.

Background The IP1-PROSTAGRAM study showed that a short, non-contrast MRI detected more significant cancers with similar rates of biopsy compared to PSA. Herein, we compare the expected and perceived burden of PSA, MRI and ultrasound as screening tests. Methods IP1-PROSTAGRAM was a prospective, population-based, paired screening study of 408 men conducted at seven UK primary care practices and two imaging centres. The screening tests were serum PSA, non-contrast MRI and ultrasound. If any test was screen-positive, a prostate biopsy was performed. Participants completed an Expected Burden Questionnaire (EBQ) and Perceived Burden Questionnaire (PBQ) before and after each screening test. Results The overall level of burden for MRI and PSA was minimal. Few men reported high levels of anxiety, burden, embarrassment or pain following either MRI or PSA. Participants indicated an overall preference for MRI after completing all screening tests. Of 408 participants, 194 (47.5%) had no preference, 106 (26.0%) preferred MRI and 79 (19.4%) preferred PSA. This indicates that prior to screening, participants preferred MRI compared to PSA (+6.6%, 95% CI 4.4–8.4, p = 0.02) and after completing screening, the preference for MRI was higher (+21.1%, 95% CI 14.9–27.1, p < 0.001). The proportion of participants who strongly agreed with repeating the test was 50.5% for ultrasound, 65% for MRI and 68% for PSA. A larger proportion of participants found ultrasound anxiety-inducing, burdensome, embarrassing and painful compared to both MRI and PSA. Conclusions Prostagram MRI and PSA are both acceptable as screening tests among men aged 50–69 years. Both tests were associated with minimal amounts of anxiety, burden, embarrassment and pain. The majority of participants preferred MRI over PSA and ultrasound. Registration This study was registered on clinicaltrials.gov at https://clinicaltrials.gov/ct2/show/NCT03702439 .

Background: The use of prostate-specific antigen (PSA) testing to screen for prostate cancer has been fraught with under-and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) might detect more grade group >= 2 cancers with similar rates of biopsy.Objective: To evaluate strategies that combined PSA and MRI to select men based in the community for a prostate biopsy.Design, setting, and participants: IP1-PROSTAGRAM was a prospective, population -based, paired cohort study of 408 men aged 50-69 yr conducted at seven UK primary care practice and two imaging centres (from October 10, 2018 to May 15, 2019).Intervention: All participants underwent screening with a PSA test, MRI (T2-weighted and diffusion), and transrectal ultrasound (b-mode and elastography). If any test was screen positive, a systematic 12-core biopsy was performed. Additional image-fusion targeted biopsies were taken if the MRI or ultrasound was positive. Outcome measurements and statistical analysis: We conducted an analysis, set out in the statistical plan a priori, comparing 13 different pathways including PSA-alone, MRI-alone, and a range of PSA thresholds and MRI scores. The performance of each path-way was evaluated focusing on the trade-offs between biopsy referral rates and detection of grade group >= 2 cancers. A targeted biopsy was performed only where the PROSTAGRAM MRI showed a lesion score of 3, 4, or 5.Results and limitations: The standard PSA pathway (PSA >= 3 ng/ml + systematic biopsy) would lead to 10% of men being referred for a biopsy and a 1.0% detection rate of grade group >= 2 cancers. Pathways that relied on MRI alone set at a threshold score of 3 for a biopsy led to higher biopsy rates, but with benefit of high cancer detection rates. The pathway that combined an initial low PSA threshold (>= 1.0 ng/ml) and MRI score >= 4 accurately identified a high rate of grade group >= 2 cancers (2.5%, 95% confidence interval 1.3-4.6) while recommending fewer patients for a biopsy (7.1%, 95% confidence interval

You have accessJournal of UrologyCME1 Apr 2023MP73-03 THE PROPORTION OF PATIENTS ELIGIBLE FOR FOCAL THERAPY OF NON-METASTATIC PROSTATE CANCER IN THE MODERN MRI-DIRECTED DIAGNOSTIC PATHWAY Deepika Reddy, David Eldred-Evans, Mathias Winkler, Taimur Shah, and Hashim Ahmed Deepika ReddyDeepika Reddy More articles by this author , David Eldred-EvansDavid Eldred-Evans More articles by this author , Mathias WinklerMathias Winkler More articles by this author , Taimur ShahTaimur Shah More articles by this author , and Hashim AhmedHashim Ahmed More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003341.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Medium-term outcomes following focal therapy for non-metastatic prostate cancer demonstrate good cancer control. There is uncertainty about what proportion of patients might be eligible for focal therapy, given the shift to an upfront MRI in the diagnostic pathway. Using four large prospective studies (PICTURE, PROMIS, IP1-PROSTAGRAM and RAPIDOnline), we evaluated how many newly diagnosed patients might be suitable for focal therapy. METHODS: Suitability was determined in a stepwise nature according to the Delphi Consensus criteria on focal therapy: PSA≤20 ng/ml, ≤rT3aN0M0, Gleason Grade Group (GGG) ≤3, if highest (GGG) was 1 then cancer length must be ≥6 mm, and treatment pattern must intend to spare at least 1 neurovascular bundle. Each study obtained local or external Research and Ethics approval. RESULTS: 201/330 (61%) recruited into PICTURE were diagnosed with≤rT3aN0 prostate cancer with PSA≤20 ng/ml of whom 119/201 (59%) were deemed suitable for focal treatment. None would have D’Amico low risk disease, 105 (88%) and 14 (12%) would have D’Amico intermediate and high-risk disease, respectively. Within PROMIS 406/740 (55%) patients had≤rT3aN0 prostate cancer and PSA≤20 ng/ml. 196/406 (48%) were focal suitable. 4 (2%), 76 (39%) and 116 (59%) had low, intermediate, and high-risk. 534/2372 (23%) in RAPID were diagnosed with≤rT3aN0 disease and PSA≤20 ng/ml. 364/534 (68%) were focal suitable. 3 (1%), 296 (82%) and 65 (18%) had low, intermediate, and high-risk. 37/411 (9%) patients recruited to IP1-PROSTAGRAM had≤rT3aN0 disease with PSA<20 ng/ml. 17/37 (46%) were focal suitable. 2 (12%) and 15 (88%) had low and intermediate-risk disease. CONCLUSIONS: Independent of varying incidence of prostate cancer within each cohorts, once diagnosed with localised disease between 5 and 7 patients out of 10 were eligible for focal treatment. Source of Funding: n/a © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1035 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Deepika Reddy More articles by this author David Eldred-Evans More articles by this author Mathias Winkler More articles by this author Taimur Shah More articles by this author Hashim Ahmed More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 Apr 2023MP40-03 CIRCULATING CHROMOSOME CONFORMATION SIGNATURES ENHANCE THE ACCURACY OF PSA FOR DETECTING PROSTATE CANCER - RESULTS FROM PERFORMANCE OF THE EPISWITCHTM PCA TEST IN THE PROSTAGRAM TRIAL Jiten Jaipuria, Dmitri Pchejetski, David Eldred-Evans, Martin J Connor, Hashim U Ahmed, Alexandre Akoulitchev, Ewan Hunter, and Mathias Winkler Jiten JaipuriaJiten Jaipuria More articles by this author , Dmitri PchejetskiDmitri Pchejetski More articles by this author , David Eldred-EvansDavid Eldred-Evans More articles by this author , Martin J ConnorMartin J Connor More articles by this author , Hashim U AhmedHashim U Ahmed More articles by this author , Alexandre AkoulitchevAlexandre Akoulitchev More articles by this author , Ewan HunterEwan Hunter More articles by this author , and Mathias WinklerMathias Winkler More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: PSA screening for prostate cancer (PCa) has a low overall accuracy despite high specificity. Novel blood biomarkers thus are prime candidates for improvement. 3-dimension chromatin conformations (CCCs) are known epigenetic regulators that manifest early in PCa tumorigenesis. EpiSwitch™ is a blood sample-based epigenetic assay developed by us which algorithmically analyses CCCs. We previously found diagnosed high-risk PCa associated with CCCSs in the loci of HSD3B2, VEGFC, APAF1, BMP6, ERG, MSR1, MUC1, ACAT1 and DAPK1 genes. Here, we evaluate the ability of EpiSwitch™ to detect PCa in a screening cohort of patients in the Prostagram trial. METHODS: We created a population cohort (n=147) of men, 50-69 years of age, comprising 109 volunteers participating in PCa screening in the Prostagram trial, and enriched it hospital tissue bank samples of 29 men with established localised PCa, and 9 cancer-negative controls. The cohort was then randomly split into training and testing groups in a 1:2 ratio. Samples were tested for PSA and the presence of CCCSs via the EpiSwitch™ assay. Batch adjustment by reference alignment procedure was used to control for batch effects. Feature engineering of the EpiSwitch™ markers with PSA was performed by recursive feature elimination using linear discriminant analysis, xgbtree, xgblinear, decision trees and random forest libraries in the R program. Shapley additive explanations values were used to quantify the contribution of each feature within the model. XGBoost algorithm model was used for final test optimisation and ultimately the EpiSwitch™PCa test was created. We compared combinations of - binary PSA threshold (>3 ng/ml), continuous PSA, and EpiSwitch™PCa-in terms of accuracy, positive (PPV) and negative predictive values (NPV) to determine PCa in the Prostagram cohort. RESULTS: ERG21 marker was discarded during the test optimisation to create the EpiSwitch™PCa assay. PSA>3ng/ml had a low PPV of 0.14 and a high NPV of 0.93 in the Prostagram cohort. Episwitch™PCa alone showed a PPV of 0.91 and NPV of 0.32. EpiSwitch™PCa combined with PSA>3ng/ml had a PPV of 0.81 and NPV of 0.78. However, EpiSwitch™PCa combined with continuous PSA yielded a remarkable PPV of 0.92, and NPV of 0.94, with an overall accuracy of 0.94. CONCLUSIONS: Combining the PSA test with specific CCCs in the blood has a potential for rapid PCa diagnosis with very high accuracy and low cost justifying further research in a prospective blinded cohort study. Source of Funding: Cost of the epigenetic assay was funded by Oxford biodynamics. Prostagram study was funded by the Wellcome trust. Data was analysed by Oxford biodynamics within the a priori statistical analysis plan of the Prostagram study. Analysis was performed with oversight of an independent academic statistician from the Prostagram study trial management group. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e545 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jiten Jaipuria More articles by this author Dmitri Pchejetski More articles by this author David Eldred-Evans More articles by this author Martin J Connor More articles by this author Hashim U Ahmed More articles by this author Alexandre Akoulitchev More articles by this author Ewan Hunter More articles by this author Mathias Winkler More articles by this author Expand All Advertisement PDF downloadLoading ...

Objective To compare biopsy recommendation rates and accuracy of the Prostate Imaging‐Reporting and Data System, version 2 (PI‐RADSv2) with the Likert scale for detection of clinically significant and insignificant prostate cancer in men screened within the Imperial Prostate 1 Prostate Cancer Screening Trial Using Imaging (IP1‐PROSTAGRAM). Patients and Methods Men aged 50–69 years were screened with Prostagram MRI. Scans were prospectively reported using both PI‐RADSv2 (excluding dynamic contrast‐enhanced sequence score) and 5‐point Likert scores by expert uro‐radiologists. Systematic and targeted transperineal biopsy was recommended if the scan was scored ≥ 3, based on either reporting system. The proportion of patients recommended for biopsy and detection rates for Grade Groups (GGs) 1 and ≥ 2 were compared. Receiver operating characteristic (ROC) analysis was performed to compare performance. Results A total of 406 men underwent Prostagram MRI. The median (interquartile range) age and prostate‐specific antigen level were 57 (53–61) years and 0.91 (0.56–1.74) ng/mL, respectively. At MRI score ≥ 3, more patients were recommended for biopsy based on Likert criteria (94/406; 23%, 95% confidence interval [CI] 19.2%–27.6%) compared to PI‐RADSv2 (72/406; 18%, 95% CI 14.2%–21.9%; P = 0.03). For MRI scores ≥ 4, PI‐RADSv2 and Likert scales led to 43/406 (11%, 95% CI 7.9%–14.1%) and 35/406 (9%, 95% CI 6.2%–11.9%) men recommended for biopsy ( P = 0.40). For GG ≥ 2 detection, PIRADSv2 and Likert detected 22% (95% CI 11.4%–30.8%, 14/72) and 16% (95% CI 9.5%–25.3%, 15/94), respectively ( P = 0.56). For GG1 cancers detection these were 11% (95% CI 4.3%–19.6%, seven of 72) vs 11% (95% CI 4.7%–17.8%, nine of 94; P = 1.00). The accuracy of PI‐RADSv2 and Likert scale was similar (area under the ROC curve 0.64 vs 0.65, P = 0.95). Conclusions In reporting non‐contrast‐enhanced Prostagram MRI in a screening population, the PI‐RADSv2 and Likert scoring systems were equally accurate; however, Likert scale use led to more men undergoing biopsy without a subsequent increase in significant cancer detection rates. To improve reporting of Prostagram MRI, either the PI‐RADSv2 or a modified Likert scale or a standalone scoring system should be developed.