Prostatic arterial embolization versus holmium laser enucleation of the prostate: 1-year outcomes.

PURPOSE: Holmium Laser Enucleation of the Prostate (HoLEP) and Prostatic Artery Embolization (PAE) are novel techniques for the treatment of benign prostatic hyperplasia lower urinary tract symptoms (BPH-LUTS). The objective of this study was to describe and compare the functional results and complications of these two techniques at one year follow-up. MATERIALS AND METHODS: We performed a retrospective, monocentric study of all patients consecutively treated in our center with HoLEP or PAE for symptomatic or complicated BPH between January 2016 and December 2019. Data regarding patient and perioperative characteristics, follow-up biological results, functional questionnaires and uroflowmetry were collected from medical records. RESULTS: A total of 490 and 57 patients were treated with HoLEP and PAE, respectively. The demographic and clinical characteristics of the two groups were similar. The operative time was significantly higher for PAE (p < 0.001) and hospitalization time longer after HoLEP (p = 0.0006). The urinary catheterization time was longer after PAE (p < 0.001). The prostatic volume treated was higher with HoLEP than with PAE (56% versus 26%, p < 0.001). The mean difference in IPSS from baseline to 12 months was significantly higher after HoLEP than after PAE: - 17.58 versus - 8 (p < 0.001). The mean difference in QoL-IPSS from baseline to 12 months was significantly higher after HoLEP: - 4.09 versus - 2.27 (p < 0.001). The rate of postoperative adverse events in the first three months was similar between the two groups:35% after HoLEP and 33% after PAE (p = 0.88). CONCLUSIONS: HoLEP and PAE both significantly improved BPH-LUTS, with HoLEP having an advantage over PAE.

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.

Artificial intelligence to improve cytology performance in urothelial carcinoma diagnosis: results from validation phase of the French, multicenter, prospective VISIOCYT1 trial.

PURPOSE: Cytology and cystoscopy, the current gold standard for diagnosing urothelial carcinomas, have limits: cytology has high interobserver variability with moderate or not optimal sensitivity (particularly for low-grade tumors); while cystoscopy is expensive, invasive, and operator dependent. The VISIOCYT1 study assessed the benefit of VisioCyt® for diagnosing urothelial carcinoma. METHODS: VISIOCYT1 was a French prospective clinical trial conducted in 14 centers. The trial enrolled adults undergoing endoscopy for suspected bladder cancer or to explore the lower urinary tract. Participants were allocated either Group 1: with bladder cancer, i.e., with positive cystoscopy or with negative cystoscopy but positive cytology, or Group 2: without bladder cancer. Before cystoscopy and histopathology, slides were prepared for cytology and the VisioCyt® test from urine samples. The diagnostic performance of VisioCyt® was assessed using sensitivity (primary objective, 70% lower-bound threshold) and specificity (75% lower-bound threshold). Sensitivity was also assessed by tumor grade and T-staging. VisioCyt® and cytology performance were evaluated relative to the histopathological assessments. RESULTS: Between October 2017 and December 2019, 391 participants (170 in Group 1 and 149 in Group 2) were enrolled. VisioCyt®'s sensitivity was 80.9% (95% CI 73.9-86.4%) and specificity was 61.8% (95% CI 53.4-69.5%). In high-grade tumors, the sensitivity was 93.7% (95% CI 86.0-97.3%) and in low-grade tumors 66.7% (95% CI 55.2-76.5%). Sensitivity by T-staging, compared to the overall sensitivity, was higher in high-grade tumors and lower in low-grade tumors. CONCLUSION: VisioCyt® is a promising diagnostic tool for urothelial cancers with improved sensitivities for high-grade tumors and notably for low-grade tumors.

Artificial intelligence to improve cytology performances in bladder carcinoma detection: results of the VisioCyt test.

OBJECTIVE: To explore the utility of artificial intelligence (AI) using the VisioCyt® test (VitaDX International, Rennes, France) to improve diagnosis of bladder carcinoma using voided urine cytology. PATIENTS AND METHODS: A national prospective multicentre trial (14 centres) was conducted on 1360 patients, divided in two groups. The first group included bladder carcinoma diagnosis with different histological grades and stages, and the second group included control patients based on negative cystoscopy and cytology results. The first step of this VISIOCYT1 trial focussed on algorithm development and the second step on validating this algorithm. A total of 598 patients were included in this first step, 449 patients with bladder tumours (219 high-grade and 230 low-grade) and 149 as negative controls. The VisioCyt test was compared to voided urine cytology performed by experienced uro-pathologists from each centre. RESULTS: Overall sensitivity was highly improved by the VisioCyt test compared to cytology (84.9% vs 43%). For high-grade tumours the VisioCyt test sensitivity was 92.6% vs 61.1% for the uro-pathologists. Regarding low-grade tumours, VisioCyt test sensitivity was 77% vs 26.3% for the uro-pathologists. CONCLUSION: In comparison to routine cytology, the results of the first phase of the VISIOCYT1 trial show very clear progress in terms of sensitivity, which is particularly visible and interesting for low-grade tumours. If the validation cohort confirms these results, it could lead to the VisioCyt test being considered as a very useful aid for pathologists. Moreover, as this test is in fact software based on AI, it should become more and more efficient as more data are collected.

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.

ThinPrep® imaging system-assisted vs manual screening of urinary cytology slides in the detection of the "suspicious for high-grade urothelial carcinoma" category.

BACKGROUND: The ThinPrep® Imaging System (TIS) is a Food and Drug Administration-approved review system for cervical cytopathology, where it has been shown to increase performance over manually reviewed slides. Application of the TIS to urinary cytology has only been reported in a single study, in 2013. METHODS: We aimed to compare the agreement of two cytotechnologists' and a pathologist's manual screening (dots) with the fields of view (FOVs) selected by the TIS. We also aimed to track cases in which the TIS could identify missed abnormals and reduce the false-negative fraction. Electronically marked TIS fields (EMTFs) suspicious for high-grade urothelial carcinoma (SHGUC) were controlled by follow-up cystoscopy and histology, where available. RESULTS: A total of 826 consecutive specimens were studied. Of those, 94 (11.4%) were unreadable by the TIS. There were 710 possible comparisons, of which 380 (53.5%) received no dot after manual screening. Of the 330 remaining slides, 149 (45.1%) had at least one dot matching with the TIS FOVs. After TIS reading, EMTFs were noted in 13 of 636 (2.0%) negative cytology cases. Surveillance showed that 3/13 (23.1%, 0.4% of the 710 possible comparisons) of those cases matched with high grade urothelial carcinoma (HGUC), whereas 6/13 (46.1%, 0.8% of the 710 possible comparisons) had negative follow-up at 24 months, and 4/13 (30.8%) were lost for follow-up. CONCLUSION: The TIS increases the detection rate of SHGUC cells, potentially leading to a slight decrease in the false-negative fraction, but at the expense of a slight but larger increase in the number of false-positive cases. These findings stress the importance of a careful approach to the evaluation of the FOVs.

Comparison of the performances of the ADXBLADDER test and urinary cytology in the follow-up of non-muscle-invasive bladder cancer: a blinded prospective multicentric study.

OBJECTIVE: To compare directly the performance of the ADXBLADDER test with that of cytology in the detection of non-muscle-invasive bladder cancer (NMIBC) recurrences. BACKGROUND: ADXBLADDER is a urine test based on the detection of MCM5, a DNA licensing factor expressed in all cells capable of dividing. Expression is usually restricted to the basal stem cell compartment; however, in malignancy, MCM5-expressing cells can be found throughout the epithelium. Detection of MCM5 in urine sediment can be indicative of the presence of a bladder tumour. PATIENTS AND METHODS: A multicentre prospective, blinded study was carried out from August 2017 and July 2019 at 21 European Union centres, 14 of which collected matching cytology data. Urine was collected from patients prior to cystoscopy. Urine cytology and ADXBLADDER were performed and compared to the diagnosis obtained by cystoscopy. The performance of cytology and ADXBLADDER were then compared. RESULTS: The overall performance of ADXBLADDER demonstrated a sensitivity of 51.9%, a specificity of 66.4%, and a negative predictive value (NPV) of 92%. The sensitivity of ADXBLADDER for low- and high-grade recurrences was 44.1% and 58.8%, respectively. By contrast, cytology sensitivity was 16.7%, specificity was 98% and NPV was 90.7%. Cytology sensitivity for both low- and high-grade disease was 17.6%. CONCLUSIONS: ADXBLADDER detection of both low- and high-grade NMIBC recurrence is superior to that of cytology, with ADXBLADDER able to exclude the presence of high-grade recurrence in 97.8% of cases compared to 97.1% with cytology. These results show that ADXBLADDER has promise as a more reliable alternative to urine cytology in the follow-up of NMIBC.

Diagnostic Accuracy of MCM5 for the Detection of Recurrence in Nonmuscle Invasive Bladder Cancer Followup: A Blinded, Prospective Cohort, Multicenter European Study.

PURPOSE: Detection of MCM5 containing cells in urine has been shown to be indicative of the presence of a bladder tumor on primary diagnosis. In this study we evaluate diagnostic performance of ADXBLADDER in patients undergoing cystoscopic surveillance in nonmuscle invasive bladder cancer followup. MATERIALS AND METHODS: A multicenter prospective blinded study was performed at 21 European centers with patients undergoing cystoscopy for nonmuscle invasive bladder cancer surveillance, diagnosed in the preceding 2 years. Urine was collected from all eligible patients and ADXBLADDER-MCM5 testing was performed. Performance characteristics were calculated by comparing MCM5 results to the outcome of cystoscopy plus pathological assessment. RESULTS: Of 1,431 eligible patients enrolled 127 were diagnosed with a bladder cancer recurrence. The overall sensitivity for the ADXBLADDER-MCM5 test in detecting bladder cancer recurrence was 44.9% (95% CI 36.1-54) with a 75.6% sensitivity for nonpTaLG tumors (95% CI 59.7-87.6). Specificity was 71.1% (95% CI 68.5-73.5). The overall negative predictive value was 93% (95% CI 91.2-94.5). However, ADXBLADDER was able to rule out the presence of a nonpTaLG recurrent tumor with a negative predictive value of 99.0% (95% CI 98.2-99.5). No statistically significant differences in the performance of ADXBLADDER were observed as a result of age or sex. CONCLUSIONS: This large blinded prospective study demonstrates that in the followup of patients with nonmuscle invasive bladder cancer ADXBLADDER is able to exclude the presence of the most aggressive tumors with a negative predictive value of 99%. These results indicate that ADXBLADDER could be incorporated in the followup strategy of nonmuscle invasive bladder cancer.

Risk-adapted management of low-grade bladder tumours: recommendations from the International Bladder Cancer Group (IBCG).

OBJECTIVE: To provide a contemporary update and recommendations for the diagnosis and management of low-grade non-muscle-invasive bladder cancer (BCa) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses and reviews (up to March 2019) and provide recommendations on baseline evaluations, treatment, endpoints, study design and surveillance protocols. RESULTS: Low-grade Ta BCa poses minimal risk to patients in terms of progression and disease-specific survival. Thus, to minimize patient morbidity, this entity should be managed appropriately. After initial diagnosis of low-grade Ta tumour, subsequent stable, low-grade-appearing recurrences can be managed conservatively with office cystoscopy and fulguration or even followed using an active surveillance protocol. Intravesical therapy other than single-dose peri-operative chemotherapy instillation should be used judiciously, and only after assigning appropriate risk points. Routine use of urinary cytology - other than at initial risk stratification, or for patients on active surveillance without therapy - is not recommended; and surveillance cystoscopy may be discontinued after 5 years. Clinical studies in this group of patients should focus on recurrence rates, and time to recurrence, rather than progression events. CONCLUSIONS: The International Bladder Cancer Group has developed formal recommendations regarding the diagnosis, treatment and surveillance of low-grade non-muscle-invasive BCa to minimize morbidity and encourage uniformity among studies in this disease.

Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study.

BACKGROUND: Whether multiparametric MRI improves the detection of clinically significant prostate cancer and avoids the need for systematic biopsy in biopsy-naive patients remains controversial. We aimed to investigate whether using this approach before biopsy would improve detection of clinically significant prostate cancer in biopsy-naive patients. METHODS: In this prospective, multicentre, paired diagnostic study, done at 16 centres in France, we enrolled patients aged 18-75 years with prostate-specific antigen concentrations of 20 ng/mL or less, and with stage T2c or lower prostate cancer. Eligible patients had been referred for prostate multiparametric MRI before a first set of prostate biopsies, with a planned interval of less than 3 months between MRI and biopsies. An operator masked to multiparametric MRI results did a systematic biopsy by obtaining 12 systematic cores and up to two cores targeting hypoechoic lesions. In the same patient, another operator targeted up to two lesions seen on MRI with a Likert score of 3 or higher (three cores per lesion) using targeted biopsy based on multiparametric MRI findings. Patients with negative multiparametric MRI (Likert score ≤2) had systematic biopsy only. The primary outcome was the detection of clinically significant prostate cancer of International Society of Urological Pathology grade group 2 or higher (csPCa-A), analysed in all patients who received both systematic and targeted biopsies and whose results from both were available for pathological central review, including patients who had protocol deviations. This study is registered with ClinicalTrials.gov, number NCT02485379, and is closed to new participants. FINDINGS: Between July 15, 2015, and Aug 11, 2016, we enrolled 275 patients. 24 (9%) were excluded from the analysis. 53 (21%) of 251 analysed patients had negative (Likert ≤2) multiparametric MRI. csPCa-A was detected in 94 (37%) of 251 patients. 13 (14%) of these 94 patients were diagnosed by systematic biopsy only, 19 (20%) by targeted biopsy only, and 62 (66%) by both techniques. Detection of csPCa-A by systematic biopsy (29·9%, 95% CI 24·3-36·0) and targeted biopsy (32·3%, 26·5-38·4) did not differ significantly (p=0·38). csPCa-A would have been missed in 5·2% (95% CI 2·8-8·7) of patients had systematic biopsy not been done, and in 7·6% (4·6-11·6) of patients had targeted biopsy not been done. Four grade 3 post-biopsy adverse events were reported (3 cases of prostatitis, and 1 case of urinary retention with haematuria). INTERPRETATION: There was no difference between systematic biopsy and targeted biopsy in the detection of ISUP grade group 2 or higher prostate cancer; however, this detection was improved by combining both techniques and both techniques showed substantial added value. Thus, obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinically significant prostate cancer but does not seem to avoid the need for systematic biopsy. FUNDING: French National Cancer Institute.