Continent Cutaneous Diversion: Unveiling the Interplay of Neuro-urology and Oncological Challenges.

OBJECTIVES: The objective of our study is to demonstrate the practical application of continent cutaneous urinary diversion (CCUD) in oncological patients, with a focus on various aspects of the procedure: surgical challenges, functional outcomes, and quality of life. MATERIALS AND METHODS: We studied the perioperative and follow-up data of patients who underwent cystectomy for cancer associated with CCUD (Mitrofanoff, Monti or Casale). We retrospectively analyzed complications within 30 days and beyond 30 days post-surgery. We evaluated oncological outcomes. Patients' quality of life was assessed using the Bladder Cancer Index (BCI) questionnaire. Results are given on an intention-to-treat basis. RESULTS: A total of 24 patients were included in the study (July 2001 and May 2022), with a median follow-up of 62.5 months. We report three deaths due to neoplasic recurrence. 46% had an early postoperative complication, two of whom required revision surgery. Overall, the medium-term complication rate was 83% and the reoperation rate was 62%. There were 8 stomal cutaneous stenoses (33%) and 3 uretero-ileal stenoses (12.5%). Overall satisfaction was rated at 9.2/10 on average, and body image was unaltered or slightly altered in 62.5% of patients. Of the patients who responded to the BCI, 75% had complete continence. DISCUSSION: The experience gained with continent stomas in neuro-urology has allowed, in carefully selected cases, to offer patients an alternative that can improve their quality of life in a context already burdened by the shadow of cancer. CCUD can be proposed as an alternative to Bricker diversion in cases of urethral invasion or a high risk of neobladder incontinence, in selected patients.

A collaborative review of the microsatellite instability/deficient mismatch repair phenotype in patients with upper tract urothelial carcinoma.

OBJECTIVE: To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC). METHOD: A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients. RESULTS: The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome. Indications for its investigation currently remain limited to patients with a clinical suspicion for sporadic UTUC to refer only those with a positive testing for germline DNA sequencing to screen for this syndrome. With regard to technical aspects, despite the interest of MSIsensor, only PCR and immunohistochemistry are routinely used to somatically investigate the MSI and dMMR phenotypes, respectively. The prevalence of the MSI/dMMR phenotype in UTUC patients ranges from 1.7% to 57%, depending on the study population, investigation method and definition of a positive test. Younger age and a more balanced male to female ratio at initial diagnosis are the main specific clinical characteristics of UTUC patients with an MSI/dMMR phenotype. Despite the conflicting results available in the literature, these patients may have a better prognosis, potentially related to more favourable pathological features. Finally, they may also have lower sensitivity to chemotherapy but greater sensitivity to immunotherapy. CONCLUSION: Our collaborative review summarises the available data from published studies exploring the MSI/dMMR phenotype in UTUC patients, the majority of which are limited by a low level of evidence.

Learning curve for fusion magnetic resonance imaging targeted prostate biopsy and three-dimensional transrectal ultrasonography segmentation.

OBJECTIVE: To report the learning curve of multiple operators for fusion magnetic resonance imaging (MRI) targeted biopsy and to determine the number of cases needed to achieve proficiency. MATERIALS AND METHODS: All adult males who underwent fusion MRI targeted biopsy between February 2012 and July 2021 for clinically suspected prostate cancer (PCa) in a single centre were included. Fusion transrectal MRI targeted biopsy was performed under local anaesthesia using the Koelis platform. Learning curves for segmentation of transrectal ultrasonography (TRUS) images and the overall MRI targeted biopsy procedure were estimated with locally weighted scatterplot smoothing by computing each operator's timestamps for consecutive procedures. Non-risk-adjusted cumulative sum (CUSUM) methods were used to create learning curves for clinically significant (i.e., International Society of Urological Pathology grade ≥ 2) PCa detection. RESULTS: Overall, 1721 patients underwent MRI targeted biopsy in our centre during the study period. The median (interquartile range) times for TRUS segmentation and for the MRI targeted biopsy procedure were 4.5 (3.5, 6.0) min and 13.2 (10.6, 16.9) min, respectively. Among the 14 operators with experience of more than 50 cases, a plateau was reached after 40 cases for TRUS segmentation time and 50 cases for overall MRI targeted biopsy procedure time. CUSUM analysis showed that the learning curve for clinically significant PCa detection required 25 to 45 procedures to achieve clinical proficiency. Pain scores ranged between 0 and 1 for 84% of patients, and a plateau phase was reached after 20 to 100 cases. CONCLUSIONS: A minimum of 50 cases of MRI targeted biopsy are necessary to achieve clinical and technical proficiency and to reach reproducibility in terms of timing, clinically significant PCa detection, and pain.

Management of patients with muscle-invasive bladder cancer with clinical evidence of pelvic lymph node metastases.

Identification of clinically positive pelvic lymph node metastases (cN+) in patients with muscle-invasive bladder cancer is currently challenging, as the diagnostic accuracy of available imaging modalities is limited. Conventional CT is still considered the gold-standard approach to diagnose lymph node metastases in these patients. The development of innovative diagnostic methods including radiomics, artificial intelligence-based models and molecular biomarkers might offer new perspectives for the diagnosis of cN+ disease. With regard to the treatment of these patients, multimodal strategies are likely to provide the best oncological outcomes, especially using induction chemotherapy followed by radical cystectomy and pelvic lymph node dissection in responders to chemotherapy. Additionally, the use of adjuvant nivolumab has been shown to decrease the risk of recurrence in patients who still harbour ypT2-T4a and/or ypN+ disease after surgery. Alternatively, the use of avelumab maintenance therapy can be offered to patients with unresectable cN+ tumours who have at least stable disease after induction chemotherapy alone. Lastly, patients with cN+ tumours who are not responding to induction chemotherapy are potential candidates for receiving second-line treatment with pembrolizumab.

Robot-assisted Periprostatic Artificial Urinary Sphincter Implantation in Men with Neurogenic Stress Urinary Incontinence: Description of the Surgical Technique and Comparison of Long-term Functional Outcomes with the Open Approach.

BACKGROUND: Periprostatic artificial urinary sphincter implantation (pAUSi) is a rare yet relevant indication for male neurogenic stress urinary incontinence (SUI). OBJECTIVE: To describe the surgical technique of robot-assisted pAUSi (RApAUSi) and compare the long-term functional results with the open pAUSi (OpAUSi). DESIGN, SETTING, AND PARTICIPANTS: Data of 65 consecutive men with neurogenic SUI undergoing pAUSi between 2000 and 2022 in a tertiary centre were collected retrospectively. SURGICAL PROCEDURE: Thirty-three patients underwent OpAUSi and 32 underwent RApAUSi. OpAUSi cases were performed by a single surgeon, experienced in functional urology and prosthetic surgery. RApAUSi cases were performed by the same surgeon together with a second surgeon, experienced in robotic surgery. MEASUREMENTS: Outcome measures were achievement of complete urinary continence, intra- and postoperative complications, and surgical revision-free survival (SRFS). RESULTS AND LIMITATIONS: RApAUSi showed superior results to OpAUSi in terms of median (interquartile range) operative time (RApAUSi: 170 [150-210] min vs OpAUSi: 245 [228-300] min; p < 0.001), estimated blood loss (RApAUSi: 20 [0-50] ml vs OpAUSi: 500 [350-700] ml; p < 0.001), and median length of hospital stay (LOS; RApAUSi: 5 [4-6] d vs OpAUSi: 11 [10-14] d; p < 0.001). Clavien-Dindo grade ≥3a complications occurred more frequently after OpAUSi (RApAUSi: 1/32 [3%] vs OpAUSi: 10/33 [30%]; p = 0.014). Achievement of complete urinary continence (zero pads) was comparable between the groups (RApAUSi: 24/32 [75%] vs OpAUSi: 24/33 [73%]; p = 0.500). The median follow-up periods were 118 (50-183) and 56 (25-84) mo for OpAUSi and RApAUSi, respectively (p < 0.001). A tendency towards longer SRFS was observed in the RApAUSi group (p = 0.076). The main study limitation was its retrospective nature. CONCLUSIONS: RApAUSi is an efficient alternative to OpAUSi, resulting in shorter operative times, less blood loss, fewer severe complications, and a shorter LOS with similar functional results and need for revision surgery. PATIENT SUMMARY: Compared with open periprostatic artificial urinary sphincter implantation (pAUSi), robot-assisted pAUSi leads to faster recovery and similar functional results, with fewer postoperative complications.

Perioperative, renal function and oncological outcomes of robot-assisted radical nephroureterectomy for patients with upper tract urothelial carcinoma.

PURPOSE: To report perioperative, renal function and oncological outcomes of robot-assisted radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). METHODS: This was a retrospective single-arm monocentric study including all consecutive UTUC patients treated with robot-assisted RNU at our institution between 2014 and 2022. Descriptive statistics with median and interquartile range (IQR) for continuous variables and numbers with frequencies for categorical variables were used to report perioperative and renal function outcomes while Kaplan-Meier curves were computed to present extravesical and intravesical recurrence-free survival(RFS) as well as cancer-specific (CSS) and overall survival (OS) with the corresponding 95% confidence intervals(CIs). RESULTS: Overall, 70 patients with a median age of 69.6 [63.3-74.9] years were included in our study. With regards to perioperative outcomes, the median operative time was 157 [130-182] min with a median blood loss of 200 [100-300] cc. Intraoperative complications occurred in 4 (5.7%) patients but no conversion to open or laparoscopic surgery was required. Postoperative complications occurred in 9 (12.9%) patients, including 5 (7.1%) with grade ≥ 3 complications according to the Clavien-Dindo classification. The median length of stay was 4 [3-6] days. With regards to renal function outcomes, the median postoperative loss in estimated glomerular filtration rate at discharge was 16 [10.25-26] mL/min/1.73 m2. With regards to oncological outcomes, the 3-year extravesical and intravesical RFS, CSS and OS rates were 73.6 [62.8-86.2]%, 68.1 [54.6-85]%, 82.5 [72-94.4]% and 75.3 [63.4-89.5]%, respectively. CONCLUSION: We report favorable perioperative and oncological outcomes with expected decrease in renal function after robot-assisted RNU for patients with UTUC.

Design and rationale of a single-arm phase II study of neoadjuvant Durvalumab and Gemcitabine associated with Cisplatin or Carboplatin for upper urinary tract urothelial cancer: the iNDUCT trial (NCT04617756).

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer. STUDY DESIGN AND ENDPOINTS: Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned. PATIENTS AND INTERVENTIONS: Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee.

Impact of Relative Volume Difference Between Magnetic Resonance Imaging and Three-dimensional Transrectal Ultrasound Segmentation on Clinically Significant Prostate Cancer Detection in Fusion Magnetic Resonance Imaging-targeted Biopsy.

BACKGROUND: Segmentation of three-dimensional (3D) transrectal ultrasound (TRUS) images is known to be challenging, and the clinician often lacks a reliable and easy-to-use indicator to assess its accuracy during the fusion magnetic resonance imaging (MRI)-targeted prostate biopsy procedure. OBJECTIVE: To assess the effect of the relative volume difference between 3D-TRUS and MRI segmentation on the outcome of a targeted biopsy. DESIGN, SETTING, AND PARTICIPANTS: All adult males who underwent an MRI-targeted prostate biopsy for clinically suspected prostate cancer between February 2012 and July 2021 were consecutively included. INTERVENTION: All patients underwent a fusion MRI-targeted prostate biopsy with a Koelis device. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three-dimensional TRUS and MRI prostate volumes were calculated using 3D prostate models issued from the segmentations. The primary outcome was the relative segmentation volume difference (SVD) between transrectal ultrasound and MRI divided by the MRI volume (SVD = MRI volume - TRUS volume/MRI volume) and its correlation with clinically significant prostate cancer (eg, International Society of Urological Pathology [ISUP] ≥2) positiveness on targeted biopsy cores. RESULTS AND LIMITATIONS: Overall, 1721 patients underwent a targeted biopsy resulting in a total of 5593 targeted cores. The median relative SVD was significantly lower in patients diagnosed with clinically significant prostate cancer than in those with ISUP 0-1: (6.7% [interquartile range {IQR} -2.7, 13.6] vs 8.0% [IQR 3.3, 16.4], p < 0.01). A multivariate regression analysis showed that a relative SVD of >10% of the MRI volume was associated with a lower detection rate of clinically significant prostate cancer (odds ratio = 0.74 [95% confidence interval: 0.55-0.98]; p = 0.038). CONCLUSIONS: A relative SVD of >10% of the MRI segmented volume was associated with a lower detection rate of clinically significant prostate cancer on targeted biopsy cores. The relative SVD can be used as a per-procedure quality indicator of 3D-TRUS segmentation. PATIENT SUMMARY: A discrepancy of ≥10% between segmented magnetic resonance imaging and transrectal ultrasound volume is associated with a reduced ability to detect significant prostate cancer on targeted biopsy cores.

Unleashing the Power of Artificial Intelligence and Fusion Magnetic Resonance Imaging-Targeted Biopsy: Transforming Prostate Cancer Diagnosis.

Advances in artificial intelligence (AI) and medical imaging have opened new avenues for the diagnosis and management of prostate cancer. In particular, AI technology can enhance the performance of fusion magnetic resonance imaging-targeted biopsy of the prostate, and has the potential to enhance the usability and precision of this biopsy technique, guide treatment decisions, and further advance prostate cancer care.

A Plea for the Use of Video-recorded Cystoscopy for Blinded Independent Central Review of Tumor Response in Open-label Non-muscle invasive Bladder Cancer Trials.

Given that most of non-muscle invasive bladder cancer trials available in the literature share the same limitation of an open-label design, they are likely prone to detection bias. Indeed, tumor response is currently assessed by unblinded investigators, mainly via follow-up cystoscopy, which has well-known intraobserver and interobserver variability. Thus, we believe that the use of video-recorded cystoscopy for blinded independent central review of tumor response could help to minimize detection bias in open-label NMIBC trials.

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.

A Systematic Review of Oncological Outcomes Associated with Bladder-sparing Strategies in Patients Achieving Complete Clinical Response to Initial Systemic Treatment for Localized Muscle-invasive Bladder Cancer.

CONTEXT: Bladder-sparing strategies (BSSs) have been proposed for the treatment of muscle-invasive bladder cancer (MIBC) patients achieving clinical complete response (cCR) to initial systemic treatment to avoid toxicity related to radical cystectomy. OBJECTIVE: To systematically review the current literature evaluating oncological outcomes of BSSs in patients achieving cCR to initial systemic treatment for localized MIBC. EVIDENCE ACQUISITION: A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting oncological outcomes of MIBC patients undergoing either surveillance or radiation therapy after achieving cCR to initial systemic treatment. Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 23 noncomparative prospective or retrospective studies published between 1990 and 2021. The mean bladder and metastatic recurrence rates (range) as well as the mean bladder preservation rate (BPR; range) were calculated, and overall survival (OS) was extracted from included reports. EVIDENCE SYNTHESIS: Overall, 16 and seven studies evaluated surveillance (n = 610) and radiation therapy (n = 175) in MIBC patients achieving cCR to initial systemic treatment, respectively. With regard to surveillance, the median follow-up ranged from 10 to 120 mo, with a mean bladder recurrence rate of 43% (0-71%), including 65% of non-muscle-invasive bladder cancer (NMIBC) and 35% of MIBC recurrences. The mean BPR was 73% (49-100%). The mean metastatic recurrence rate was 9% (0-27%), while 5-yr OS rates ranged from 64% to 89%. With regard to radiation therapy, the median follow-up ranged from 12 to 60 mo, with a mean bladder recurrence rate of 15% (0-29%), including 24% of NMIBC, 43% of MIBC, and 33% of unspecified recurrences. The mean BPR was 74% (71-100%). The mean metastatic recurrence rate was 17% (0-22%), while the 4-yr OS rate was 79%. CONCLUSIONS: Our systematic review showed that only low-level evidence supports the effectiveness of BSSs in selected patients achieving cCR to initial systemic treatment for localized MIBC. These preliminary findings highlight the need for further prospective comparative research to demonstrate its efficacy. PATIENT SUMMARY: We reviewed studies evaluating bladder-sparing strategies in patients achieving complete clinical response to initial systemic treatment for localized muscle-invasive bladder cancer. Based on low-level evidence, we observed that selected patients could benefit from surveillance or radiation therapy in this setting, but prospective comparative research is requested to confirm their efficacy.