Objective: To compare the efficacy of transrectal and transperineal prostate-guided biopsies to magnetic resonance imaging (MRI) index lesions in detecting clinically significant prostate cancer (csPCa), and to evaluate the role of systematic biopsies. Methods: This prospective and multicenter trial, conducted in the early detection program of csPCa of Catalonia (Spain) between 2021 and 2023, involved 4,029 men suspected of ha-ving PCa who underwent multiparametric MRI followed by guided and systematic biopsies. From this cohort, 1,376 men with reported size and localization of index lesions were selected. A matched group of 325 pairs of men subjected to transrectal and transperineal biopsy was chosen to account for confounding variables. We compared csPCa detection rates at index lesions and systematic biopsies, as well as by lesion localization. Results: Transperineal and transrectal biopsies detected csPCa in 49.5% vs. 40.6% overall (p = 0.027), 44.6% vs. 30.8% at index lesions (p = 0.001), and 24.3% vs. 35.1% at systematic biopsies (p = 0.003). CsPCa detection rates were higher in transperineal biopsies across all index lesion localizations, with significant increases in anterior zone (47.8% vs. 20.8% at mid-base, p = 0.039; 52.9% vs. 24.2% at apex, p = 0.024) and central zone (33.3% vs. 5.9%, p = 0.003). CsPCa detected only in systematic biopsies was 10.5% in transrectal biopsies and 4.9% in transperineal biopsies (p = 0.012). Conclusions: Targeted biopsies via the transperineal route showed higher csPCa detection rates than transrectal biopsies, parti-cularly for anterior and apical lesions, with systematic biopsies showing reduced utility.

Background: A transperineal approach to prostate biopsy is now recommended to reduce the risk of infectious complications associated with the transrectal route. Our aim is to compare the efficacy of transrectal- and transperineal-guided biopsies involving the magnetic resonance imaging (MRI) of index lesions in detecting significant prostate cancer (sPCas), and to evaluate the role of systematic biopsies. Methods: In a prospective and multicenter trial conducted in an opportunistic early detection program for sPCa in Catalonia (Spain), between 2021 and 2023, 4029 men suspected of having PCa underwent multiparametric MRI followed by guided and systematic biopsies. From this cohort, we retrospectively selected 1376 men with reports of the size and localization of their index lesions. A matched group of 325 pairs of men subjected to transrectal and transperineal biopsy were chosen to account for confounding variables. We compared sPCa detection rates determined via index lesions and systematic biopsies, as well as by lesion localization. Results: Transperineal and transrectal biopsies detected sPCa in 49.5% vs. 40.6% overall (p = 0.027), 44.6% vs. 30.8% from index lesions (p = 0.001), and 24.3% vs. 35.1% from systematic biopsies (p = 0.003). SPCa detection rates were higher in transperineal biopsies across all index lesion localizations, with significant increases in the anterior zone (47.8% vs. 20.8% at the mid-base, p = 0.039, and 52.9% vs. 24.2% at the apex, p = 0.024) and central zone (33.3% vs. 5.9%, p = 0.003). With regards to SPCa detected only in systematic biopsies, 10.5% of cases were detected in transrectal biopsies and 4.9% of cases were detected in transperineal biopsies (p = 0.012). Conclusions: Targeted biopsies conducted via the transperineal route showed higher sPCa detection rates than transrectal biopsies, particularly for anterior and apical lesions, with systematic biopsies showing reduced utility.

Quality control of programs for detection of significant prostate cancer (sPCa) could be defined by the correlation between observed and reference 95% confidence intervals (CIs) for Prostate Imaging-Reporting and Data System (PI-RADS) categories. We used the area under the receiver operating characteristic curve (AUC) for the Barcelona magnetic resonance imaging (MRI) predictive model to screen the quality of ten participant centers in the sPCa opportunistic early detection program in Catalonia. We set an AUC of <0.8 as the criterion for suboptimal quality. Quality was confirmed in terms of the correlation between actual sPCa detection rates and reference 95% CIs. For a cohort of 2624 men with prostate-specific antigen >3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and two- to four-core targeted biopsies of PI-RADS ≥3 lesions and/or 12-core systematic biopsy, AUC values ranged from 0.527 to 0.914 and were <0.8 in four centers (40%). There was concordance between actual sPCa detection rates and reference 95% CIs for one or two PI-RADS categories when the AUC was <0.8, and for three or four PI-RADS categories when the AUC was ≥0.8. A review of procedures used for sPCa detection should be recommended in centers with suboptimal quality. Patient summary: We tested a method for assessing quality control for centers carrying out screening for early detection of prostate cancer. We found that the method can identify centers that may need to review their procedures for detection of significant prostate cancer.

Since the optimal scheme for targeted biopsies of magnetic resonance imaging (MRI) suspicious lesions remains unclear, we compare the efficacy of two schemes for these index lesions. A prospective trial was conducted in 1161 men with Prostate Imaging Reporting and Data System v 2.1 3–5 undergoing targeted and 12-core systematic biopsy in four centers between 2021 and 2023. Two- to four-core MRI-transrectal ultrasound fusion-targeted biopsies via the transperineal route were conducted in 900 men in three centers, while a mapping per 0.5 mm core method (saturated scheme) was employed in 261 men biopsied in another center. A propensity-matched 261 paired cases were selected for avoiding confounders other than the targeted biopsy scheme. CsPCa (grade group ≥ 2) was identified in 125 index lesions (41.1%) when the two- to four-core scheme was employed, while in 187 (71.9%) when the saturated biopsy (p < 0.001) was used. Insignificant PCa (iPCa) was detected in 18 and 11.1%, respectively (p = 0.019). Rates of csPCa and iPCa remained similar in systematic biopsies. CsPCa detected only in systematic biopsies were 5 and 1.5%, respectively (p = 0.035) in each group. The saturated scheme for targeted biopsies detected more csPCa and less iPCa than did the two- to four-core scheme in the index lesions. The rate of csPCa detected only in the systematic biopsies decreased when the saturated scheme was employed.

PURPOSE:To validate the Barcelona magnetic resonance imaging predictive model (BCN-MRI PM) in men with pre-biopsy multiparametric MRI (mpMRI) reported with the Prostate Imaging Reporting and Data System (PI-RADS) v2.1, followed by transrectal and transperineal prostate biopsies. MATERIALS AND METHODS:Prospective analysis of 3,264 men with PSA >3.0 ng/mL and/or abnormal digital rectal examination who were referred to ten participant centers in the csPCa early detection program of Catalonia (Spain), between 2021 and 2023. MpMRI was reported with the PI-RADS v2.1, and 2- to 4-core MRI-transrectal ultrasound (TRUS) fusion-targeted biopsy of suspected lesions and/or 12-core systematic biopsy were conducted. 2,295 (70.3%) individuals were referred to six centers for transrectal prostate biopsies, while 969 (39.7%) were referred to four centers for transperineal prostate biopsies. CsPCa was classified whenever the International Society of Urologic Pathology grade group was 2 or higher. RESULTS:CsPCa was detected in 41% of transrectal prostate biopsies and in 45.9% of transperineal prostate biopsies (p < 0.016). Both BCN-MRI PM calibration curves were within the ideal correlation between predicted and observed csPCa. Areas under the curve and 95% confidence intervals were 0.847 (0.830-0.857) and 0.830 (0.823-0.855), respectively (p = 0.346). Specificities corresponding to 95% sensitivity were 37.6 and 36.8%, respectively (p = 0.387). The Net benefit of the BCN-MRI PM was similar with both biopsy methods. CONCLUSIONS:The BCN-MRI PM has been successfully validated when mpMRI was reported with the PI-RADS v2.1 and prostate biopsies were conducted via the transrectal and transperineal route.

The role of digital rectal examination (DRE) in the early detection of significant prostate cancer (PCa) is being questioned in the era of magnetic resonance imaging (MRI). However, some men with suspected PCa may still be identified solely through DRE, even with low serum prostate-specific antigen (PSA) levels. Additionally, most predictive models designed to improve significant PCa diagnostic pathways incorporate DRE findings. We assessed the role of DRE among 5005 men with serum PSA levels > 3.0 ng/mL and/or suspicious DRE findings, who underwent pre-biopsy MRI and targeted and/or systematic biopsies, as part of the significant PCa opportunistic screening program in Catalonia (Spain) between 2016 and 2023. Significant PCa, defined as grade group > 2, was detected in 2097 men (41.9%). Suspicion of PCa was based solely on DRE in 206 cases (4.1%) with significant PCa detected in 50 of them (2.4%). Two pathways using the Barcelona predictive models, before and after MRI, with and without DRE findings showed specificities of 52.8 and 38.7%, respectively (p < 0.001), after fixing sensitivity at 90%. Prostate biopsy was avoided in 35.1 and 26.7%, respectively (p < 0.001), while its efficacy increased from 52.8 to 58%. We conclude that DRE improved the effectiveness of an opportunistic significant PCa-screening program.

PURPOSE:To analyze the reduction in multiparametric magnetic resonance imaging (mpMRI) demand and prostate biopsies after the hypothetical implementation of the Barcelona risk-stratified pathway (BCN-RSP) in a population of the clinically significant prostate cancer (csCaP) early detection program in Catalonia.MATERIALS AND METHODS:A retrospective comparation between the hypothetical application of the BCN-RSP and the current pathway, which relied on pre-biopsy mpMRI and targeted and/or systematic biopsies, was conducted. The BCN-RSP stratify men with suspected CaP based on a prostate specific antigen (PSA) level >10 ng/ml and a suspicious rectal examination (DRE), and the Barcelona-risk calculator 1 (BCN-RC1) to avoid mpMRI scans. Subsequently, candidates for prostate biopsy following mpMRI are selected based on the BCN-RC2. This comparison involved 3,557 men with serum PSA levels > 3.0 ng/ml and/or suspicious DRE. The population was recruited prospectively in 10 centers from January 2021 and December 2022. CsCaP was defined when grade group ≥ 2.RESULTS:CsCaP was detected in 1,249 men (35.1%) and insignificant CaP was overdeteced in 498 (14%). The BCN-RSP would have avoid 705 mpMRI scans (19.8%), and 697 prostate biopsies (19.6%), while 61 csCaP (4.9%) would have been undetected. The overdetection of insignificant CaP would have decrease in 130 cases (26.1%), and the performance of prostate biopsy for csCaP detection would have increase to 41.5%.CONCLUSION:The application of the BCN-RSP would reduce the demand for mpMRI scans and prostate biopsies by one fifth while less than 5% of csCaP would remain undetected. The overdetection of insignificant CaP would decrease by more than one quarter and the performance of prostate biopsy for csCaP detection would increase to higher than 40%.

Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate cancer (csPCa) detection. Our objective is to analyze the effect of 5-ARI on the prostate imaging–reporting and data system (PI-RADS) distribution and csPCa and insignificant PCa (iPCa) detection. Among 2212 men with serum prostate-specific antigen levels of >3.0 ng/mL and/or suspicious digital rectal examinations who underwent mpMRI and targeted and/or systematic biopsies, 120 individuals exposed to 5-ARI treatment for over a year were identified. CsPCa was defined when the grade group (GG) was >2. The overall csPCa and iPCa detection rates were 44.6% and 18.8%, respectively. Since logistic regression revealed independent predictors of PCa, a randomized matched group of 236 individuals was selected for analysis. The PI-RADS distribution was comparable with 5-ARI exposure (p 0.685). The CsPCa detection rates in 5-ARI-naïve men and 5-ARI-exposed men were 52.6% and 47.4%, respectively (p 0.596). IPCa was detected in 37.6 and 62.5%, respectively (p 0.089). The tumor GG distribution based on 5-ARI exposure was similar (p 0.149) to the rates of csPCa and iPCa across the PI-RADS categories. We conclude that exposure to 5-ARI in suspected PCa men did not change the PI-RADS distribution and the csPCa and iPCa detection rates.

PURPOSE:To relate the prostate volume category (PVC) assessed with digital rectal examination (DRE)-small, median, and large-and the prostate volumes (PVs) assessed with magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). To compare the clinically significant prostate cancer (csPCa) discrimination ability of two predictive models based on DRE-PVC and MRI-PV.MATERIALS AND METHODS:A prospective trial of 2,090 men with prostate-specific antigen >3 ng/mL and/or PCa suspicious DRE were prospectively recruited in 10 centers from Catalonia (Spain), between 2021 and 2022, in whom DRE-PVC was assessed. Pre-biopsy MRI, and 12-core TRUS-random biopsy was always performed after 2- to 6-core TRUS-fusion targeted biopsy of prostate imaging-report and data system >3 lesions. In 370 men (17.7%) the DRE-PVC was unconclusive. Among the 1,720 men finally analyzed the csPCa (grade group >2) detection was 42.4%.RESULTS:The median (interquartile range) of TRUS and MRI-PVs of small prostates were 33 mL (19-37 mL) and 35 mL (23-30 mL), p=0.410; in median prostates they were 51 mL (38-58 mL) and 55 mL (48-63 mL) respectively, p<0.001; in large prostates 80 mL (60-100 mL) and 95 mL (75-118 mL) respectively, p<0.001. The predictive models sharing the MRI-PV and DRE-PVC showed areas under the curves of 0.832 (95% confidence interval [CI], 0.813-0.851) and 0.828 (95% CI, 0.809-0.848) respectively, p=0.632, as well as similar net benefit and clinical utility.CONCLUSIONS:PVC was unconclusive in 17% of DREs. MRI-PV overestimated the TRUS-PV in median and large prostates. The predictive models based on MRI-PV and DRE-PVC showed similar efficacy to predict csPCa. PVC assessed with DRE is helpful to predict the csPCa risk before MRI.

To validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI). A population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7

Background: Magnetic resonance imaging (MRI)-based risk calculators (MRI-RCs) individualise the likelihood of clinically significant prostate cancer (csPCa) and improve candidate selection for prostate biopsy beyond the Prostate Imaging Reporting and Data System (PI-RADS). Objective: To compare the Barcelona (BCN) and Rotterdam (ROT) MRI-RCs in an entire population and according to the PI-RADS categories. Design, setting, and participants: A prospective comparison of BCN-and ROT-RC in 946 men with suspected prostate cancer in whom systematic biopsy was per-formed, as well as target biopsies of PI-RADS >3 lesions. Outcome measurements and statistical analysis: Saved biopsies and undetected csPCa (grade group >2) were determined. Results and limitations: The csPCa detection was 40.8%. The median risks of csPCa from BCN-and ROT-RC were, respectively, 67.1% and 25% in men with csPCa, whereas 10.5% and 3% in those without csPCa (p < 0.001). The areas under the curve were 0.856 and 0.844, respectively (p = 0.116). BCN-RC showed a higher net benefit and clinical utility over ROT-RC. Using appropriate thresholds, respectively, 75% and 80% of biopsies were needed to identify 50% of csPCa detected in men with PI-RADS <3, whereas 35% and 21% of biopsies were saved, missing 10% of csPCa detected in men with PI-RADS 3. BCN-RC saved 15% of biopsies, missing 2% of csPCa in men with PI-RADS 4, whereas ROT-RC saved 10%, missing 6%. No RC saved biopsies without missing csPCa in men with PI-RADS 5. Conclusions: ROT-RC provided a lower and narrower range of csPCa probabilities than BCN-RC. BCN-RC showed a net benefit over ROT-RC in the entire population. However, BCN-RC was useful in men with PI-RADS 3 and 4, whereas ROT-RC was useful only in those with PI-RADS 3. No RC seemed to be helpful in men with neg-ative MRI and PI-RADS 5. Patient summary: Barcelona risk calculator was more helpful than Rotterdam risk calculator to select candidates for prostate biopsy. & COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).

PURPOSE:This study evaluated the performance of a drop-in gamma probe for prostate cancer (PCa) sentinel lymph node dissection (SLND) in a pelvic phantom, porcine model, and in PCa patients as part of an ongoing prospective multicenter clinical trial. METHODS:Two design variants of the drop-in gamma probe (SENSEI; Lightpoint Medical Ltd) were assessed in the pelvic phantom, and the preferred design was evaluated in a porcine model with clinically representative volumes and 99mTc activities. In the clinical trial, radical prostatectomy, SLND, and extended pelvic lymph node dissection were performed the day after 99mTc-nanocolloid injection and imaging. Sentinel lymph nodes (SLNs) were detected with the drop-in probe and a rigid laparoscopic gamma probe (RLGP). An interim analysis was performed after 10 patients were recruited. RESULTS:The narrow field of view probe design outperformed the wide field of view design in the pelvic phantom (detection rate, 100% vs 50%). In the porcine model, all activity concentrations could be successfully detected. The drop-in gamma probe successfully detected SLNs in all 10 patients (detection rate, 100%). Two of the SLNs identified by the drop-in gamma probe could not be found with the RLGP. No false-negative cases and no adverse events related to the SLND procedure or the drop-in gamma probe occurred. CONCLUSION:The drop-in gamma probe meets the usability and performance requirements for SLND in PCa and provides performance advantages over the RLGP. The final clinical study results will confirm the performance of the technique across multiple sites.

BJUI CompassEarly View RESEARCH LETTEROpen Access A risk-organised model for clinically significant prostate cancer early detection Juan Morote, Corresponding Author Juan Morote [email protected] orcid.org/0000-0002-2168-323X Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain Department of Surgery, Universitat Autònoma de Barcelona, Barcelona, Spain Department of Urology, Hospital Miguel Servet, IIS-Aragon, Zaragoza, Spain Correspondence Juan Morote, Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain. Email: [email protected]Search for more papers by this authorÁngel Borque-Fernando, Ángel Borque-Fernando orcid.org/0000-0003-0178-4567 Department of Urology, Hospital Miguel Servet, IIS-Aragon, Zaragoza, SpainSearch for more papers by this authorMarina Triquell, Marina Triquell Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain Department of Surgery, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorJosé M. Abascal, José M. Abascal Department of Urology, Parc de Salut Mar, Barcelona, Spain Department of Surgery, Universitat Pompeu Fabra, Barcelona, SpainSearch for more papers by this authorPol Servian, Pol Servian Department of Urology, Hospital Germans Trias i Pujol, Badalona, SpainSearch for more papers by this authorJacques Planas, Jacques Planas Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain Department of Surgery, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorOlga Mendez, Olga Mendez Urology Biomedical Research Unit, Vall d'Hebron Research Institute, Barcelona, SpainSearch for more papers by this authorLuis M. Esteban, Luis M. Esteban Department of Applied Mathematics, Escuela Universitaria Politécnica La Almunia, Universidad de Zaragoza, Zaragoza, SpainSearch for more papers by this authorEnrique Tilla, Enrique Tilla orcid.org/0000-0001-9401-0872 Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain Department of Surgery, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this author Juan Morote, Corresponding Author Juan Morote [email protected] orcid.org/0000-0002-2168-323X Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain Department of Surgery, Universitat Autònoma de Barcelona, Barcelona, Spain Department of Urology, Hospital Miguel Servet, IIS-Aragon, Zaragoza, Spain Correspondence Juan Morote, Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain. Email: [email protected]Search for more papers by this authorÁngel Borque-Fernando, Ángel Borque-Fernando orcid.org/0000-0003-0178-4567 Department of Urology, Hospital Miguel Servet, IIS-Aragon, Zaragoza, SpainSearch for more papers by this authorMarina Triquell, Marina Triquell Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain Department of Surgery, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorJosé M. Abascal, José M. Abascal Department of Urology, Parc de Salut Mar, Barcelona, Spain Department of Surgery, Universitat Pompeu Fabra, Barcelona, SpainSearch for more papers by this authorPol Servian, Pol Servian Department of Urology, Hospital Germans Trias i Pujol, Badalona, SpainSearch for more papers by this authorJacques Planas, Jacques Planas Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain Department of Surgery, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this authorOlga Mendez, Olga Mendez Urology Biomedical Research Unit, Vall d'Hebron Research Institute, Barcelona, SpainSearch for more papers by this authorLuis M. Esteban, Luis M. Esteban Department of Applied Mathematics, Escuela Universitaria Politécnica La Almunia, Universidad de Zaragoza, Zaragoza, SpainSearch for more papers by this authorEnrique Tilla, Enrique Tilla orcid.org/0000-0001-9401-0872 Department of Urology, Vall d'Hebron Hospital, Barcelona, Spain Department of Surgery, Universitat Autònoma de Barcelona, Barcelona, SpainSearch for more papers by this author First published: 07 March 2023 https://doi.org/10.1002/bco2.230 Juan Morote and Ángel Borque-Fernando have equal contribution as first author. Luis M. Esteban and Enrique Tilla have equal contribution as last author. 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Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Evidence that specific mortality of PCa decrease when clinically significant PCa (csPCa) is early detected has moved the focus of PCa screening towards csPCa.1 This paradigm shift has occurred since the spread of multiparametric magnetic resonance imaging (mpMRI), which allows to avoid unnecessary prostate biopsies and overdetection of insignificant PCa (iPCa) in a cost-effective way.2, 3 However, because suspicion of PCa remains based on elevated serum prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE), there has been an increased demand for mpMRI that cannot always be performed. In experienced centres, biparametric MR has replaced mpMRI, reducing scan time by a quarter and maintaining the reproducibility and accuracy of the Prostate Imaging Reporting and Data System (PI-RADS).1 The recommendation of prostate biopsy is currently made according to the PI-RADS category. Experienced radiologists, reporting with an updated version of PI-RADS, obtain a negative predictive value of mpMRI that reaches up to 95%, which makes it possible to avoid prostate biopsies in men with suspected PCa with a PI-RADS <3. MRI-targeted biopsies of suspicious lesions (PI-RADS ≥3) improve the sensitivity of systematic biopsies for csPCa. However, uncertain scenarios after mpMRI, having high rates of unnecessary biopsies and/or overdetection of iPCa, remain, and then PSA density (PSAD), new markers and predictive models are recommended to improve the selection of candidates for prostate biopsy.4 The European Association of Urology currently recommends the design of csPCa risk-organised models (ROMs) by sequencing available tools to reduce the demand of mpMRI exams, and unnecessary prostate biopsies ones mpMRI is performed.1 Because prostate volume is a powerful predictor of csPCa and usually transrectal ultrasound is not performed to assess prostate volume before mpMRI, its assessment through DRE-prostate volume category is now recommended.5 There is also evidence that men with serum PSA higher than 10 ng/mL and abnormal DRE do not benefit from MRI-targeted biopsies, since systematic biopsies can detect all existing csPCa.6 The Barcelona-risk calculator 1 (BCN RC-1) has been developed and externally validated to individualise the risk of csPCa to avoid the demand of mpMRI exams,7 as well as the BCN-RC 2 to predict the risk of csPCa after mpMRI and avoid unnecessary biopsies.7 Both risk calculators are available at https://mripcaprediction.shinyapps.io/MRIPCaPrediction/. The present study aims to compare the current standard approach for early detection of csPCa, based on MRI-targeted biopsies when PI-RADS lesions ≥3 and systematic biopsy,1 with a ROM designed to avoiding mpMRI exams in men with serum PSA over than 10.0 ng/mL and abnormal DRE, in addition to rule out mpMRI exams when the risk of csPCa from the BCN-RC 1 is lower than 12%.6, 7 Once mpMRI is performed, prostate biopsy will be scheduled in men having a risk of csPCa from the BCN-RC 2 higher than 4%.8 The selection of proposed thresholds was made to avoid missing no more than 10% of csPCa detected. The 95% csPCa sensitivity thresholds of BCN RC-1 and BCN RC-2, in those men in whom they were applied, were selected. A probability analysis of avoiding mpMRI exams and prostate biopsies as well as missed csPCa has been performed. A series of 946 men with serum PSA > 3.0 ng/mL and/or abnormal DRE was recruited prospectively in two academic centres of cities from the Barcelona metropolitan area (PSM and GTiP), between January 1 of 2018 and December 31 of 2021. This series was independent from those for the development of BCN-RC 1 and BCN-RC 2 recruited at VHH, between January 1 of 2016 and December 31 of 2019.7, 8 All men were scheduled to 3-T mpMRI and two- to four-core transrectal ultrasound (TRUS) cognitive MRI-targeted biopsies to PI-RADSv.2 ≥ 3 lesions and 12-core TRUS systematic biopsy; 12-core TRUS systematic biopsy was performed when PI-RADSv.2 < 3. This project was approved by the institutional ethics committee of VHH (PRAG-317/2017), and the analysis was performed on anonymised databases. CsPCa, defined as the International Society of Uro-pathology grade group 2 or higher, was detected in 386 men (40.8%). The median age of participants was 67 years with an interquartile range (IQR) between 61 and 75. The median serum PSA was 7.2 ng/mL (IQR: 5.5–10.9), 32.5% of participants had abnormal DRE, and 31% had previous negative prostate biopsy. CsPCa was detected in 17.9% of the 235 men with PI-RADS <3 (24.8%); in 20.4% of the 301 men with PI-RADS 3 (21.2%); in 51.9% of the men with PI-RADS 4 (12.6%); and 84% of those with PI-RADS 5 (12.6%). In the subset of 124 men with serum PSA > 10.0 ng/mL and abnormal DRE, csPCa was detected in 106 (85.6%). The probability analyses of the standard approach and the proposed ROM are presented in Figure 1. The standard approach required mpMRI in all participants, 235 (24.8%) of prostate biopsies were avoided in those men with PI-RADS <3, and 42 (10.9%) of overall csPCa detected were missed. Among the 711 participants biopsied (75.2%) csPCa was detected in 344 (48.4%). The proposed ROM initially ruled out mpMRI in 124 men with serum PSA > 10.0 ng/mL and abnormal DRE (13.1% of all participants), in whom systematic biopsies identified all 106 csPCa detected, which represented 27.5% of all csPCa detected. The BCN-RC 1 ruled out mpMRI exams in 167 men (17.7%), missing 13 csPCa (3.4%). After mpMRI, performed in 655 men (69.2%), the BCN RC-2 ruled out prostate biopsy in 100 men, in whom 13 detected csPCa were missed (3.4%). Among the 555 men finally biopsied (63.3%), csPCa was detected in 254 (45.8%). The ROM would rule out 30.8% of mpMRI exams, and 28.2% of prostate biopsies, whereas 6.7% of overall csPCa would be undetected. FIGURE 1Open in figure viewerPowerPoint Flow chart description of standard approach of csPCa, and the proposed risk-organised model, with intermediate and overall results according to rule out mpMRI exams, avoided prostate biopsies and missed csPCa detection. Data are expressed in number and (%) of all MRI exams and prostate biopsies performed and csPCa detected. Abbreviations: BCN, Barcelona; csPCa, clinically significant PCa; DRE, digital rectal examination; mpMRI, multiparametric magnetic resonance imaging; PB, prostate biopsies; PCa, prostate cancer; PI-RADS, Prostate Imaging Report and Data System; PSA, prostate-specific antigen; RC, risk calculator. aProposed thresholds. The proposed ROM was able to rule out almost one-third of mpMRI exams and the percentage of saved biopsies increased from the 24.8% observed with the standard approach to the 28.2%, whereas the percentage of undetected csPCa decreased from 10.9 to 6.7 respectively. Remmers et al. have recently reported the results with an ROM based on sequencing the Rotterdam RC-3 and the Rotterdam MRI-RC in the MRI arm of the PRECISION trial, which was carried out in biopsy-naïve men. After recalibration and adjustment of csPCa thresholds in both predictive models, this ROM was able to rule out 13% of mpMRI exams, decreasing the number of prostate biopsies in 9% and missing 8.5% of csPCa detected in the 134 men with PI-RADS ≥3 in whom MRI-targeted biopsies of suspicious lesions and systematic biopsy were performed.9 The present study confirms the effectiveness of the proposed ROM to improve the early detection of csPCa by reducing the demand of mpMRI exams and unnecessary prostate biopsies. The missing rate of csPCa of the standard approach that avoids systematic biopsy in men with negative mpMRI also decreased. The main limitation for the use of the proposed ROM is the need of validation in the populations where it will be implemented. Now, following the recommendation of EAU, this ROM is ready to be used in the metropolitan area of Barcelona, and validation in Catalonia (Spain), a country with seven and half million inhabitants, is ongoing. Ideally, a randomised trial would be necessary to generate high evidence level. AUTHOR CONTRIBUTIONS Juan Morote, Ángel Borque-Fernando and Luis M. Esteban conceptualised the idea. Marina Triquell, José M. Abascal, Pol Servian, Jacques Planas, Olga Mendez and Enrique Tilla developed the concept. Juan Morote wrote the first draft of the manuscript. All authors were involved in editing, critical review and final approval of the manuscript. ACKNOWLEDGEMENTS The Instituto de Salut Carlos III (SP) and European Union financed this project, ref. PI20/01666. CONFLICT OF INTEREST STATEMENT The authors have no conflict of interest to declare. REFERENCES 1Van Poppel H, Hogenhout R, Albers P, van den Bergh RCN, Barentsz JO, Roobol MJ. A European model for an organised risk-stratified early detection Programme for prostate cancer. Eur Urol Oncol. 2021; 4(5): 731– 9. https://doi.org/10.1016/j.euo.2021.06.006 2Schoots IG, Padhani AR, Rouvière O, Barentsz JO, Richenberg J. Analysis of magnetic resonance imaging-directed biopsy strategies for changing the paradigm of prostate cancer diagnosis. Eur Urol Oncol. 2020; 3(1): 32– 41. https://doi.org/10.1016/j.euo.2019.10.001 3Donato P, Morton A, Yaxley J, Teloken PE, Coughlin G, Esler R, et al. Improved detection and reduced biopsies: The effect of a multiparametric magnetic resonance imaging-based triage prostate cancer pathway in a public teaching hospital. World J Urol. 2020; 38(2): 371– 9. https://doi.org/10.1007/s00345-019-02774-y 4Osses DF, Roobol MJ, Schoots IG. Prediction medicine: Biomarkers, risk calculators and magnetic resonance imaging as risk stratification tools in prostate cancer diagnosis. Int J Mol Sci. 2019; 20(7):1637. https://doi.org/10.3390/ijms20071637 5Roobol MJ, van Vugt HA, Loeb S, Zhu X, Bul M, Bangma CH, et al. Prediction of prostate cancer risk: The role of prostate volume and digital rectal examination in the ERSPC risk calculators. Eur Urol. 2012; 61(3): 577– 83. https://doi.org/10.1016/j.eururo.2011.11.012 6Morote J, Celma A, Roche S, de Torres IM, Mast R, Semedey ME, et al. Who benefits from multiparametric magnetic resonance imaging after suspicion of prostate cancer. Eur Urol Oncol. 2019; 2(6): 664– 9. https://doi.org/10.1016/j.euo.2018.11.009 7Morote J, Borque-Fernando Á, Triquell M, Campistol M, Celma A, Regis L, et al. A clinically significant prostate cancer predictive model using digital rectal examination prostate volume category to stratify initial prostate cancer suspicion and reduce magnetic resonance imaging demand. Cancers (Basel). 2022; 14(20):5100. https://doi.org/10.3390/cancers14205100 8Morote J, Borque-Fernando A, Triquell M, Celma A, Regis L, Escobar M, et al. The Barcelona predictive model of clinically significant prostate cancer. Cancers (Basel). 2022; 14(6):1589. https://doi.org/10.3390/cancers14061589 9Remmers S, Kasivisvanathan V, Verbeek JFM, Moore CM, Roobol MJ, ERSPC RSGPRECISIONIG. Reducing biopsies and magnetic resonance imaging scans during the diagnostic pathway of prostate cancer: Applying the Rotterdam prostate cancer risk calculator to the PRECISION trial data. Eur Urol Open Sci. 2022; 36: 1– 8. https://doi.org/10.1016/j.euros.2021.11.002 Early ViewOnline Version of Record before inclusion in an issue FiguresReferencesRelatedInformation

The European Association of Urology currently recommends the use of risk-organized models to decrease the demand of prebiopsy magnetic resonance imaging (MRI) and unnecessary prostate biopsies in men with suspected prostate cancer (CaP). Low evidence suggests that men with prostate-specific antigen >10 ng/ml and an abnormal digital rectal examination (DRE) do not benefit from prebiopsy MRI and targeted biopsies. We aim to validate this low evidence in a sizable cohort and knowing how many clinically significant CaP (csCaP) would go undetected if only random biopsies were performed in these cases. We analyze a subset of 545 men with PSA >10 ng/ml and an abnormal DRE who met the previous criteria among 5,329 participants in a prospective trial in whom random biopsy was always performed and targeted biopsies of PI-RADS ≥3 lesions (10.2%). CsCaP (grade group ≥2) was detected in 370 men (67.9%), with 11 of 49 with negative MRI (22.5%) and 359 of 496 (72.4%) having PI-RADS ≥3. CsCaP was identified in random and targeted biopsies in 317 (88.7%) men, in targeted biopsies only in 23 (6.4%), and in random biopsies only in 19 (5.3%). If only random biopsies were performed in these men, 23 of overall 1,914 csCaP (1.2%) would go undetected in this population. Prebiopsy MRI can be saved in men with serum PSA >10 ng/ml and an abnormal DRE and only random biopsy performed. However, a close follow-up of men with negative random biopsy seems appropriate due to the high-risk of csCaP in these men.

The primary objective of this study was to analyse the current accuracy of targeted and systematic prostate biopsies in detecting csPCa. A secondary objective was to determine whether there are factors predicting the finding of csPCa in targeted biopsies and, if so, to explore the utility of a predictive model for csPCa detection only in targeted biopsies. We analysed 2122 men with suspected PCa, serum PSA > 3 ng/mL, and/or a suspicious digital rectal examination (DRE), who underwent targeted and systematic biopsies between 2021 and 2022. CsPCa (grade group 2 or higher) was detected in 1026 men (48.4%). Discrepancies in csPCa detection in targeted and systematic biopsies were observed in 49.6%, with 13.9% of csPCa cases being detected only in systematic biopsies and 35.7% only in targeted biopsies. A predictive model for csPCa detection only in targeted biopsies was developed from the independent predictors age (years), prostate volume (mL), PI-RADS score (3 to 5), mpMRI Tesla (1.5 vs. 3.0), TRUS-MRI fusion image technique (cognitive vs. software), and prostate biopsy route (transrectal vs. transperineal). The csPCa discrimination ability of targeted biopsies showed an AUC of 0.741 (95% CI 0.721-0.762). The avoidance rate of systematic prostate biopsies went from 0.5% without missing csPCa to 18.3% missing 4.6% of csPCa cases. We conclude that the csPCa diagnostic accuracy of targeted biopsies is higher than that of systematic biopsies. However, a significant rate of csPCa remains detected only in systematic biopsies. A predictive model for the partial omission of systematic biopsies was developed.

ObjectivesTo determine the accuracy of nodal staging in patients with prostate cancer (PCa) when 99mTc-nanocolloid radiotracer is injected into an index lesion (IL).MethodsThis prospective study was conducted at our institution between June 2016 and October 2020. It included 64 patients with localized PCa with at least a 5% possibility for lymph node involvement in the Memorial Sloan Kettering Cancer Center nomogram, suitable for surgical treatment. All patients underwent magnetic resonance imaging (MRI) with IL and were pathologically confirmed. The day before surgery, transrectal ultrasound-guided injection (TRUS) of 99mTc-nanocolloid into the IL was performed. Surgical procedures included radical prostatectomy (RP), sentinel lymph node biopsy (SLNB), and extended pelvic lymphadenectomy (ePLND). Analysis was performed, including histopathological findings of RP, ePLND, and SLNB. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false negative (FN), false positive (FP), diagnostic yield, and non-diagnostic rate were calculated.ResultsA total of 1,316 lymph nodes were excised, including 1,102 from the ePLND (83.7%) and 214 (16.3%) sentinel lymph nodes (SLN). 26 SLN were dissected outside the ePLND template. The final pathology demonstrated 46 (3.5%) lymph node metastasis, 31 (67.4%) in the SLNB and 15 (32.6%) in the non-SLN ePLND. At the patient level, 18 (28.1%) patients had pN1. With a mean follow-up of 33.1 months, 4/19 (21.1%) pN1 patients had undetectable PSA, and 3/19 (15.8%) had a PSA < 0.1 ng/mL. Lymph node dissection included 20.6 lymph nodes per patient (IQR 15–24.2), with 3.3 SLNB nodes per patient (IQR 2–4.2). PPV and NPV were 100 and 97.8%, respectively. Sensitivity and specificity were 94.4 and 100%, respectively. FN was 5.5% and FP was 4.3%. Diagnostic yields were 95.3% and the non-diagnostic rate was 4.7%.ConclusionRadiotracer injection into the prostate IL offers promising results for staging purposes in cases in which ePLND is considered. Negative SLNB is a predictor of negative ePLND. Patients with a limited burden of nodal metastasis have a significant chance of remaining free of biochemical recurrence at mid-term follow-up.

Se ha descrito que la timoglobulina podría aumentar el riesgo de infecciones y neoplasias, en comparación con basiliximab. La leucocitopenia y la trombocitopenia también son más frecuentes en los primeros días tras el trasplante en los pacientes tratados con timoglobulina. Nuestro objetivo fue analizar las complicaciones hemorrágicas en este subconjunto de pacientes. Se evaluaron las complicaciones hemorrágicas en 515 trasplantes renales realizados en nuestra institución entre 2012 y 2018. Se comparó a los pacientes tratados con timoglobulina (grupo 1, N = 91) con los tratados con basiliximab (grupo 2, N = 424). Encontramos diferencias en cuanto al descenso plaquetario: 95.142,2 (55.339,6) en el grupo 1 y 52.364,3 (69.116,6) en el grupo 2 (p = 0,001), número de pacientes con trombocitopenia grave (< 7.5000/mm3) (20,8% vs. 3,7%, p = 0,001), número de concentrados de hematíes transfundidos (3,25 [0,572] vs. 2,2 [0,191], p = 0,028) y porcentaje de pacientes que requirieron reintervención por sangrado (18,2% vs. 7,7%, p = 0,046). En un análisis multivariable de regresión lineal múltiple (la variable dependiente fue el número de concentrado de hematíes transfundidos), solo la edad (OR 0,037, IC del 95%, 0,003-0,070) y el tipo de inmunosupresión (OR 1,592, IC del 95%, 1,38-2,84) tuvieron significación estadística. El uso de timoglobulina en el período perioperatorio del trasplante podría aumentar las complicaciones hemorrágicas. En nuestra serie, la trombocitopenia grave y el sangrado activo que requirió reintervención, fueron 6 y 2,5 veces más frecuente, respectivamente, en el grupo de pacientes con timoglobulina. En lugar de suspender el uso de este agente inmunosupresor, se podría ajustar la dosis para continuar con el tratamiento. Se debe evaluar el uso de timoglobulina en el postoperatorio de estos pacientes. It has been described that thymoglobulin could increase the risk of infections and malignancies, in comparison to basiliximab. Leukopenia and thrombocytopenia are also more common within the first days after transplantation among thymoglobulin patients. Our objective was to analyze bleeding complications in this subset of patients. Bleeding complications were evaluated among 515 renal transplants carried out at our institution between 2012 and 2018. We compared patients treated with thymoglobulin (Group 1, N = 91) with those treated with basiliximab (Group 2, N = 424). We found differences in platelet decrease:95142.2 (55,339.6) in Group 1 and 52,364.3 (69,116.6) in Group 2 (P=.001), number of patients with severe thrombocytopenia (<75,000/mm3) (20.8% vs. 3.7%, P=.001), number of blood units transfused (3.25 (0.572) vs. 2.2 (0.191, P=.028) and percentage of patients that required surgery due to bleeding (18.2% vs. 7.7%, P=.046). In a multiple lineal regression multivariable analysis (dependent variable was number of blood units transfused), only age [OR 0.037, 95% CI (0.003-0.070)] and type of immunosuppression [OR 1.592, 95% CI (1.38-2.84)] showed statistical significance. The use of thymoglobulin in the perioperative transplantation period could increase bleeding complications. In our series, in the group of patients with thymoglobulin, severe thrombocytopenia was 6 times more frequent, and active bleeding that required surgery was also 2.5 times more frequent. One way to continue with the use of this immunosuppression agent, might be to adjust the dose instead of discontinuing it. The use of thymoglobulin should be a factor to consider in the postoperative period of these patients.