Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

BACKGROUND AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI. METHODS: The lesions targeted at biopsy in the MRI-FIRST dataset were retrospectively delineated and assessed using a previously developed algorithm. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score assigned prospectively before biopsy and the algorithm score calculated retrospectively in the regions of interest were compared for diagnosing GG ≥2 cancer, using the areas under the curve (AUCs), and sensitivities and specificities calculated with predefined thresholds (PIRADSv2 scores ≥3 and ≥4; algorithm scores yielding 90% sensitivity in the training database). Ten predefined biopsy strategies were assessed retrospectively. KEY FINDINGS AND LIMITATIONS: After excluding 19 patients, we analysed 232 patients imaged on 16 different scanners; 85 had GG ≥2 cancer at biopsy. At patient level, AUCs of the algorithm and PI-RADSv2 were 77% (95% confidence interval [CI]: 70-82) and 80% (CI: 74-85; p = 0.36), respectively. The algorithm's sensitivity and specificity were 86% (CI: 76-93) and 65% (CI: 54-73), respectively. PI-RADSv2 sensitivities and specificities were 95% (CI: 89-100) and 38% (CI: 26-47), and 89% (CI: 79-96) and 47% (CI: 35-57) for thresholds of ≥3 and ≥4, respectively. Using the PI-RADSv2 score to trigger a biopsy would have avoided 26-34% of biopsies while missing 5-11% of GG ≥2 cancers. Combining prostate-specific antigen density, the PI-RADSv2 and algorithm's scores would have avoided 44-47% of biopsies while missing 6-9% of GG ≥2 cancers. Limitations include the retrospective nature of the study and a lack of PI-RADS version 2.1 assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The algorithm provided robust results in the multicentre multiscanner MRI-FIRST database and could help select patients for biopsy. PATIENT SUMMARY: An artificial intelligence-based algorithm aimed at diagnosing aggressive cancers on prostate magnetic resonance imaging showed results similar to expert human assessment in a prospectively acquired multicentre test database.

Passive Elastography for Clinical HIFU Lesion Detection.

High-intensity Focused Ultrasound (HIFU) is a promising treatment modality for a wide range of pathologies including prostate cancer. However, the lack of a reliable ultrasound-based monitoring technique limits its clinical use. Ultrasound currently provides real-time HIFU planning, but its use for monitoring is usually limited to detecting the backscatter increase resulting from chaotic bubble appearance. HIFU has been shown to generate stiffening in various tissues, so elastography is an interesting lead for ablation monitoring. However, the standard techniques usually require the generation of a controlled push which can be problematic in deeper organs. Passive elastography offers a potential alternative as it uses the physiological wave field to estimate the elasticity in tissues and not an external perturbation. This technique was adapted to process B-mode images acquired with a clinical system. It was first shown to faithfully assess elasticity in calibrated phantoms. The technique was then implemented on the Focal One® clinical system to evaluate its capacity to detect HIFU lesions in vitro (CNR = 9.2 dB) showing its independence regarding the bubbles resulting from HIFU and in vivo where the physiological wave field was successfully used to detect and delineate lesions of different sizes in porcine liver. Finally, the technique was performed for the very first time in four prostate cancer patients showing strong variation in elasticity before and after HIFU treatment (average variation of 33.0 ± 16.0 % ). Passive elastography has shown evidence of its potential to monitor HIFU treatment and thus help spread its use.

Zone-specific computer-aided diagnosis system aimed at characterizing ISUP ≥ 2 prostate cancers on multiparametric magnetic resonance images: evaluation in a cohort of patients on active surveillance.

PURPOSE: To assess a region-of-interest-based computer-assisted diagnosis system (CAD) in characterizing aggressive prostate cancer on magnetic resonance imaging (MRI) from patients under active surveillance (AS). METHODS: A prospective biopsy database was retrospectively searched for patients under AS who underwent MRI and subsequent biopsy at our institution. MRI lesions targeted at baseline biopsy were retrospectively delineated to calculate the CAD score that was compared to the Prostate Imaging-Reporting and Data System (PI-RADS) version 2 score assigned at baseline biopsy. RESULTS: 186 patients were selected. At baseline biopsy, 51 and 15 patients had International Society of Urological Pathology (ISUP) grade ≥ 2 and ≥ 3 cancer respectively. The CAD score had significantly higher specificity for ISUP ≥ 2 cancers (60% [95% confidence interval (CI): 51-68]) than the PI-RADS score (≥ 3 dichotomization: 24% [CI: 17-33], p = 0.0003; ≥ 4 dichotomization: 32% [CI: 24-40], p = 0.0003). It had significantly lower sensitivity than the PI-RADS ≥ 3 dichotomization (85% [CI: 74-92] versus 98% [CI: 91-100], p = 0.015) but not than the PI-RADS ≥ 4 dichotomization (94% [CI:85-98], p = 0.104). Combining CAD findings and PSA density could have avoided 47/184 (26%) baseline biopsies, while missing 3/51 (6%) ISUP 2 and no ISUP ≥ 3 cancers. Patients with baseline negative CAD findings and PSAd < 0.15 ng/mL2 who stayed on AS after baseline biopsy had a 9% (4/44) risk of being diagnosed with ISUP ≥ 2 cancer during a median follow-up of 41 months, as opposed to 24% (18/74) for the others. CONCLUSION: The CAD could help define AS patients with low risk of aggressive cancer at baseline assessment and during subsequent follow-up.

Robot Partial Prostatectomy for Anterior Cancer: Long-term Functional and Oncological Outcomes at 7 Years.

Partial prostatectomy has been described as an alternative to focal ablation therapy for the management of localized low- to intermediate-risk prostate cancer. This report aims to describe the long-term outcomes in a series of 28 men (2000-2022) who underwent robotic-assisted anterior partial prostatectomy (APP) for anteriorly located tumors entirely or partially within the anterior fibromuscular stroma. The median follow-up is 7 yr (interquartile range [IQR]: 4.2-8). The median prostate-specific antigen (PSA) before APP was 9.6 (6-11). Continence remained uninterrupted in 92% of patients. Erectile function without drug remained uninterrupted in 69%. The median nadir PSA after APP was 0.36 ng/ml (IQR: 0.25-0.60). Cancer recurrence at biopsies at the margins of the primary cancer resected area in case of a PSA elevation was observed in eight patients and led to salvage completion robotic radical prostatectomy at a median time of 3.25 yr (IQR: 2.4-6). Freedom from post-APP cancer recurrence at 7 yr was 62.7% (35.0-81.3%). Pre-APP tumor volume at magnetic resonance imaging (MRI) and volume of grade 4/5 were predictive of recurrence. Freedom from biochemical recurrence after completion radical prostatectomy at 7 yr was 94.7% (68.1-99.3%). All 28 patients are alive. No one had systemic treatment or metastases. These results confirm our initial report of robotic APP with good functional results and acceptable oncological results. The use of the inclusion criteria of pre-APP tumor volume at MRI <3 cc may decrease the risk of recurrence. Patient summary: In this report, we looked at outcomes for infrequent cases of anterior prostate cancer treated with anterior partial prostatectomy, an uncommon surgical procedure as an alternative to in situ focal ablation therapy, to better preserve functional outcomes as compared with whole gland therapy. We found that functional outcomes of uninterrupted continence and erectile function were good. Out of 28 patients, eight had recurrence in the remaining prostate and were treated with a second surgical procedure, radical prostatectomy, which was feasible. We conclude that this new technique is feasible with good functional results and acceptable oncological results, which can be shared with the patients.

Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Characterization of high-grade prostate cancer at multiparametric MRI using a radiomic-based computer-aided diagnosis system as standalone and second reader.

PURPOSE: The purpose of this study was to develop and test across various scanners a zone-specific region-of-interest (ROI)-based computer-aided diagnosis system (CAD) aimed at characterizing, on MRI, International Society of Urological Pathology (ISUP) grade≥2 prostate cancers. MATERIALS AND METHODS: ROI-based quantitative models were selected in multi-vendor training (265 pre-prostatectomy MRIs) and pre-test (112 pre-biopsy MRIs) datasets. The best peripheral and transition zone models were combined and retrospectively assessed in internal (158 pre-biopsy MRIs) and external (104 pre-biopsy MRIs) test datasets. Two radiologists (R1/R2) retrospectively delineated the lesions targeted at biopsy in test datasets. The CAD area under the receiver operating characteristic curve (AUC) for characterizing ISUP≥2 cancers was compared to that of the Prostate Imaging-Reporting and Data System version2 (PI-RADSv2) score prospectively assigned to targeted lesions. RESULTS: The best models used the 25th apparent diffusion coefficient (ADC) percentile in transition zone and the 2nd ADC percentile and normalized wash-in rate in peripheral zone. The PI-RADSv2 AUCs were 82% (95% confidence interval [CI]: 74-87) and 86% (95% CI: 81-91) in the internal and external test datasets respectively. They were not different from the CAD AUCs obtained with R1 and R2 delineations, in the internal (82% [95% CI: 76-89], P = 0.95 and 85% [95% CI: 78-91], P = 0.55) and external (82% [95% CI: 74-91], P = 0.41 and 86% [95% CI:78-95], P = 0.98) test datasets. The CAD yielded sensitivities of 86-89% and 90-91%, and specificities of 64-65% and 69-75% in the internal and external test datasets respectively. CONCLUSION: The CAD performance for characterizing ISUP grade≥2 prostate cancers on MRI is not different from that of PI-RADSv2 score across two test datasets.

Characterization of high-grade prostate cancer at multiparametric MRI: assessment of PI-RADS version 2.1 and version 2 descriptors across 21 readers with varying experience (MULTI study).

OBJECTIVE: To assess PI-RADSv2.1 and PI-RADSv2 descriptors across readers with varying experience. METHODS: Twenty-one radiologists (7 experienced (≥ 5 years) seniors, 7 less experienced seniors and 7 juniors) assessed 240 'predefined' lesions from 159 pre-biopsy multiparametric prostate MRIs. They specified their location (peripheral, transition or central zone) and size, and scored them using PI-RADSv2.1 and PI-RADSv2 descriptors. They also described and scored 'additional' lesions if needed. Per-lesion analysis assessed the 'predefined' lesions, using targeted biopsy as reference; per-lobe analysis included 'predefined' and 'additional' lesions, using combined systematic and targeted biopsy as reference. Areas under the curve (AUCs) quantified the performance in diagnosing clinically significant cancer (csPCa; ISUP ≥ 2 cancer). Kappa coefficients (κ) or concordance correlation coefficients (CCC) assessed inter-reader agreement. RESULTS: At per-lesion analysis, inter-reader agreement on location and size was moderate-to-good (κ = 0.60-0.73) and excellent (CCC ≥ 0.80), respectively. Agreement on PI-RADSv2.1 scoring was moderate (κ = 0.43-0.47) for seniors and fair (κ = 0.39) for juniors. Using PI-RADSv2.1, juniors obtained a significantly lower AUC (0.74; 95% confidence interval [95%CI]: 0.70-0.79) than experienced seniors (0.80; 95%CI 0.76-0.84; p = 0.008) but not than less experienced seniors (0.74; 95%CI 0.70-0.78; p = 0.75). As compared to PI-RADSv2, PI-RADSv2.1 downgraded 17 lesions/reader (interquartile range [IQR]: 6-29), of which 2 (IQR: 1-3) were csPCa; it upgraded 4 lesions/reader (IQR: 2-7), of which 1 (IQR: 0-2) was csPCa. Per-lobe analysis, which included 60 (IQR: 25-73) 'additional' lesions/reader, yielded similar results. CONCLUSIONS: Experience significantly impacted lesion characterization using PI-RADSv2.1 descriptors. As compared to PI-RADSv2, PI-RADSv2.1 tended to downgrade non-csPCa lesions, but this effect was small and variable across readers.

Artificial intelligence algorithms aimed at characterizing or detecting prostate cancer on MRI: How accurate are they when tested on independent cohorts? - A systematic review.

PURPOSE: The purpose of this study was to perform a systematic review of the literature on the diagnostic performance, in independent test cohorts, of artificial intelligence (AI)-based algorithms aimed at characterizing/detecting prostate cancer on magnetic resonance imaging (MRI). MATERIALS AND METHODS: Medline, Embase and Web of Science were searched for studies published between January 2018 and September 2022, using a histological reference standard, and assessing prostate cancer characterization/detection by AI-based MRI algorithms in test cohorts composed of more than 40 patients and with at least one of the following independency criteria as compared to the training cohort: different institution, different population type, different MRI vendor, different magnetic field strength or strict temporal splitting. RESULTS: Thirty-five studies were selected. The overall risk of bias was low. However, 23 studies did not use predefined diagnostic thresholds, which may have optimistically biased the results. Test cohorts fulfilled one to three of the five independency criteria. The diagnostic performance of the algorithms used as standalones was good, challenging that of human reading. In the 12 studies with predefined diagnostic thresholds, radiomics-based computer-aided diagnosis systems (assessing regions-of-interest drawn by the radiologist) tended to provide more robust results than deep learning-based computer-aided detection systems (providing probability maps). Two of the six studies comparing unassisted and assisted reading showed significant improvement due to the algorithm, mostly by reducing false positive findings. CONCLUSION: Prostate MRI AI-based algorithms showed promising results, especially for the relatively simple task of characterizing predefined lesions. The best management of discrepancies between human reading and algorithm findings still needs to be defined.

En Bloc Kidney Transplantation: A Retrospective Study of an 18-year Experience in a Single Institution.

Background: Renal transplantation is facing a shortage of grafts. En bloc kidney transplantation (EBKT) from pediatric donors could increase the number of available grafts. Objective: To describe the surgical technique as well as the long-term functional and morphological results of EBKT. Design setting and participants: We performed a retrospective study of all the EBKT procedures performed in Lyon between 2002 and 2020. Electronic medical records were checked with an analysis of demographics, and peri- and postoperative results. Outcome measurements and statistical analysis: A descriptive analysis of donor and recipient characteristics, perioperative data, complications, and renal function was performed. Results and limitations: Between 2002 and 2020, 21 EBKT procedures were performed. Donors had a mean weight of 8.6 kg and a mean age of 12 mo, with a mean cold ischemia time of 11 h and 30 min. Receivers had a mean age of 30 yr and a body mass index of 20. The mean follow-up time was 62 mo, with patient survival of 100% and graft survival of 95%. There were 13 reinterventions comprising one early unilateral transplantectomy for thrombosis. Renal function was excellent, and the morphological findings described an important growth in size in the first 2 yr before attaining the adult size. This study's limitations include its retrospective nature and a small number of participants. Conclusions: The present study reports excellent results with EBKT and supports the pursuit and spread of this technique. Patient summary: In this report, we describe the technique and results of en bloc kidney transplantation. We found that results are excellent for renal function and patient survival. We conclude that en bloc kidney transplantation should be considered to increase the number of grafts.

Detection of ISUP ≥2 prostate cancers using multiparametric MRI: prospective multicentre assessment of the non-inferiority of an artificial intelligence system as compared to the PI-RADS V.2.1 score (CHANGE study).

INTRODUCTION: Prostate multiparametric MRI (mpMRI) has shown good sensitivity in detecting cancers with an International Society of Urological Pathology (ISUP) grade of ≥2. However, it lacks specificity, and its inter-reader reproducibility remains moderate. Biomarkers, such as the Prostate Health Index (PHI), may help select patients for prostate biopsy. Computer-aided diagnosis/detection (CAD) systems may also improve mpMRI interpretation. Different prototypes of CAD systems are currently developed under the Recherche Hospitalo-Universitaire en Santé / Personalized Focused Ultrasound Surgery of Localized Prostate Cancer (RHU PERFUSE) research programme, tackling challenging issues such as robustness across imaging protocols and magnetic resonance (MR) vendors, and ability to characterise cancer aggressiveness. The study primary objective is to evaluate the non-inferiority of the area under the receiver operating characteristic curve of the final CAD system as compared with the Prostate Imaging-Reporting and Data System V.2.1 (PI-RADS V.2.1) in predicting the presence of ISUP ≥2 prostate cancer in patients undergoing prostate biopsy. METHODS: This prospective, multicentre, non-inferiority trial will include 420 men with suspected prostate cancer, a prostate-specific antigen level of ≤30 ng/mL and a clinical stage ≤T2 c. Included men will undergo prostate mpMRI that will be interpreted using the PI-RADS V.2.1 score. Then, they will undergo systematic and targeted biopsy. PHI will be assessed before biopsy. At the end of patient inclusion, MR images will be assessed by the final version of the CAD system developed under the RHU PERFUSE programme. Key secondary outcomes include the prediction of ISUP grade ≥2 prostate cancer during a 3-year follow-up, and the number of biopsy procedures saved and ISUP grade ≥2 cancers missed by several diagnostic pathways combining PHI and MRI findings. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Comité de Protection des Personnes Nord Ouest III (ID-RCB: 2020-A02785-34). After publication of the results, access to MR images will be possible for testing other CAD systems. TRIAL REGISTRATION NUMBER: NCT04732156.

Combined model-based and deep learning-based automated 3D zonal segmentation of the prostate on T2-weighted MR images: clinical evaluation.

OBJECTIVE: To train and to test for prostate zonal segmentation an existing algorithm already trained for whole-gland segmentation. METHODS: The algorithm, combining model-based and deep learning-based approaches, was trained for zonal segmentation using the NCI-ISBI-2013 dataset and 70 T2-weighted datasets acquired at an academic centre. Test datasets were randomly selected among examinations performed at this centre on one of two scanners (General Electric, 1.5 T; Philips, 3 T) not used for training. Automated segmentations were corrected by two independent radiologists. When segmentation was initiated outside the prostate, images were cropped and segmentation repeated. Factors influencing the algorithm's mean Dice similarity coefficient (DSC) and its precision were assessed using beta regression. RESULTS: Eighty-two test datasets were selected; one was excluded. In 13/81 datasets, segmentation started outside the prostate, but zonal segmentation was possible after image cropping. Depending on the radiologist chosen as reference, algorithm's median DSCs were 96.4/97.4%, 91.8/93.0% and 79.9/89.6% for whole-gland, central gland and anterior fibromuscular stroma (AFMS) segmentations, respectively. DSCs comparing radiologists' delineations were 95.8%, 93.6% and 81.7%, respectively. For all segmentation tasks, the scanner used for imaging significantly influenced the mean DSC and its precision, and the mean DSC was significantly lower in cases with initial segmentation outside the prostate. For central gland segmentation, the mean DSC was also significantly lower in larger prostates. The radiologist chosen as reference had no significant impact, except for AFMS segmentation. CONCLUSIONS: The algorithm performance fell within the range of inter-reader variability but remained significantly impacted by the scanner used for imaging. KEY POINTS: • Median Dice similarity coefficients obtained by the algorithm fell within human inter-reader variability for the three segmentation tasks (whole gland, central gland, anterior fibromuscular stroma). • The scanner used for imaging significantly impacted the performance of the automated segmentation for the three segmentation tasks. • The performance of the automated segmentation of the anterior fibromuscular stroma was highly variable across patients and showed also high variability across the two radiologists.

Rectourethral Fistula Induced by Localised Prostate Cancer Treatment: Surgical and Functional Outcomes of Transperineal Repair with Gracilis Muscle Flap Interposition.

BACKGROUND: Transperineal repair of rectourethral fistula (RUF) following prostate cancer treatment with gracilis muscle flap interposition (GMFI) leads to favourable outcomes, but published data are still lacking, notably concerning functional aspects. OBJECTIVE: To assess surgical and functional outcomes of this treatment of RUF. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study was conducted in two referral hospitals including 21 patients who underwent RUF transperineal repair with GMFI between 2008 and 2020. SURGICAL PROCEDURE: The standard vertical perineal approach is performed for fistula dissection. Bladder and rectal defects are closed separately. After dissection from its facia, the flap is harvested, preserving its pedicle; it is brought to the perineum and placed between the urethra and the rectum to fully cover the sutures. MEASUREMENTS: Fistula closure (clinical data and postoperative cystography), digestive stoma closure, and complications graded according to the Clavien-Dindo classification were reviewed. Functional results were assessed using the Urinary Symptom Profile (USP) questionnaire, anal incontinence St Mark's score, Patient Observer Scar Assessment Scale (POSAS) score, and a nonvalidated Likert scale questionnaire assessing issues with lower extremity functionality. RESULTS AND LIMITATIONS: The median (interquartile range) follow-up was 27 (8-47) mo. Fistula closure was successful for 20 patients (95% success). Digestive stoma was closed in 10/12 shunted patients (83%). Two (9%) Clavien-Dindo grade ≥3b complications were reported (one urinoma in a kidney transplant patient and one thigh haematoma evacuation). Eighteen patients (86%) completed the postoperative questionnaire; 11/18 (61%) had significant urinary incontinence. The mean (standard deviation) USP dysuria score was 1/9 (1.2), mean St Mark's score was 5/24 (5), mean POSAS score was 19/70 (11), mean lower extremity functionality score was 2/20 (4), and mean procedure patient satisfaction score was 9/10 (2). The retrospective design and limited number of patients are the main limitations. CONCLUSIONS: The present study found an excellent success rate and low morbidity for RUF transperineal repair with GMFI. Functional outcomes were satisfactory despite a high urinary incontinence rate. PATIENT SUMMARY: We performed an analysis of the outcomes of perineal approach surgery with muscle interposition for closing abnormal communication between the bladder and the rectum after prostate cancer treatment. This surgical technique was found to be safe to perform and provides a high success rate, with patients being satisfied despite poor urinary continence outcomes.

Her2 Expression in Circulating Tumor Cells Is Associated with Poor Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer.

HER2-dependent signaling may support the development of metastatic castration-resistant prostate cancer (mCRPC) by activating androgen receptor signaling through ligand-independent mechanisms. From 41 mCRPC patients (including 31 treated with Androgen Receptor Signaling Inhibitors [ARSI]), Circulating Tumor Cells (CTCs) were prospectively enriched with AdnaTest platform and analyzed with a multiplexed assay for HER2 and AR-V7 mRNA expression. Then, we evaluated the impact of HER2 expression on PSA-response, Progression Free Survival (PFS) and Overall Survival (OS). HER2 expression was detected in CTCs of 26 patients (63%). Although PSA response was similar regardless of HER2 status, patients with HER2 positive CTCs had shorter PSA-PFS (median: 6.2 months versus 13.0 months, p = 0.034) and radiological-PFS (6.8 months versus 25.6 months, p = 0.022) than patients without HER2 expression. HER2 expression was also associated with a shorter OS (22.7 months versus not reached, p = 0.05). In patients treated with ARSI, multivariate analyses revealed that the prognostic impact of HER2 status on PSA-PFS was independent of AR-V7 expression and of the detection of CTCs by an AdnaTest. We showed for the first time the poor prognostic value of HER2 expression in CTCs from patients with mCRPC. The therapeutic interest of targeting this actionable pathway remains to be explored.

International Multi-Site Initiative to Develop an MRI-Inclusive Nomogram for Side-Specific Prediction of Extraprostatic Extension of Prostate Cancer.

BACKGROUND: To develop an international, multi-site nomogram for side-specific prediction of extraprostatic extension (EPE) of prostate cancer based on clinical, biopsy, and magnetic resonance imaging- (MRI) derived data. METHODS: Ten institutions from the USA and Europe contributed clinical and side-specific biopsy and MRI variables of consecutive patients who underwent prostatectomy. A logistic regression model was used to develop a nomogram for predicting side-specific EPE on prostatectomy specimens. The performance of the statistical model was evaluated by bootstrap resampling and cross validation and compared with the performance of benchmark models that do not incorporate MRI findings. RESULTS: Data from 840 patients were analyzed; pathologic EPE was found in 320/840 (31.8%). The nomogram model included patient age, prostate-specific antigen density, side-specific biopsy data (i.e., Gleason grade group, percent positive cores, tumor extent), and side-specific MRI features (i.e., presence of a PI-RADSv2 4 or 5 lesion, level of suspicion for EPE, length of capsular contact). The area under the receiver operating characteristic curve of the new, MRI-inclusive model (0.828, 95% confidence limits: 0.805, 0.852) was significantly higher than that of any of the benchmark models (p < 0.001 for all). CONCLUSIONS: In an international, multi-site study, we developed an MRI-inclusive nomogram for the side-specific prediction of EPE of prostate cancer that demonstrated significantly greater accuracy than clinical benchmark models.

Salvage High-Intensity Focused Ultrasound for Local Recurrence in the Prostatic Bed after Prostatectomy and Adjuvant or Salvage Radiotherapy: Preliminary Results.

PURPOSE: We sought to report the preliminary results of salvage high-intensity focused ultrasound for locally recurrent prostate cancer in the prostatic bed after radical prostatectomy and adjuvant or salvage radiotherapy. MATERIALS AND METHODS: We retrospectively analyzed a single-center cohort of men treated with salvage high-intensity focused ultrasound for locally recurrent prostate cancer after radical prostatectomy and adjuvant or salvage radiotherapy. All patients had a combination of choline positron emission tomography, multiparametric magnetic resonance imaging, and transrectal biopsies to confirm the local recurrence. Treatment failure was defined as persistent or recurrent prostate cancer in the prostatic bed and/or metastasis and/or introduction of systemic treatment. Progression was defined as metastasis and/or introduction of systemic treatment. Complications (Clavien-Dindo classification) and continence (Ingelman-Sundberg score) were evaluated. Kaplan-Meier analysis estimated oncological outcomes. RESULTS: Between July 2009 and November 2018, 22 patients were included; the median followup was 2.32 years. At 3 years, treatment failure-free survival rate was estimated to be 49.7% and progression-free survival rate 60.4%. Prostate specific antigen nadir ≤0.2 ng/ml was reached in 50% of the patients. A nadir of ≤0.2 ng/ml was significantly associated with better treatment failure-free and progression-free survival probabilities (p=0.003 and p=0.037, respectively). Grade III complications occurred in 6 patients (27.3%). Onset of grade II-III incontinence was significantly more frequent in cases of perianastomotic (36.4%) compared to retrovesical recurrence (0%; p=0.027). CONCLUSIONS: Salvage high-intensity focused ultrasound for locally recurrent prostate cancer after radical prostatectomy and salvage radiotherapy showed encouraging oncological results despite significant morbidity. The perianastomotic recurrence was linked to a higher risk of incontinence.