[Current state of knowledge of urology residents and fellows on the neuro-urological management of spina bifida patients in France]. / État des lieux des connaissances des internes et chefs de clinique d'urologie sur la prise en charge neuro-urologique des patients spina bifida en France.

OBJECTIVE: To assess the current knowledge of French urology residents and fellows about neurogenic lower urinary tract dysfunction and their management in patients with spina bifida. MATERIAL AND METHOD: A 7-question questionnaire, covering the responder's experience and the various stages in the neuro-urological management of spina bifida, was drafted by an expert urologist. Responses were collected within 5days of being e-mailed to members of the Association française des urologues en formation (AFUF), and a descriptive analysis was carried out. RESULTS: Of the 448 members, 155 completed the questionnaire. Of the participants, 83.8% said they knew the definition of spina bifida, and 76.8% had already had to care for a spina bifida patient. Of the participants, 48.4% correctly estimated the number of spina bifida patients in France. Neurogenic lower urinary tract dysfunction to look for and the specificities of management seemed to have been acquired by a majority of respondents (correct response rates of 70.7% and 75.4%, respectively), unlike the extra-urological aspects (53.9%), and the choice of examinations useful for the initial work-up and follow-up (55.8%). CONCLUSION: While the expected neurogenic lower urinary tract dysfunction and the specificities of therapeutic management of spina bifida patients appear to be well known to urologists in training, knowledge of extra-urological symptoms and the choice of examinations could be improved. These results could be used to adjust the teaching given to French urologists in training on the urological management of spina bifida patients. LEVEL OF EVIDENCE: Grade 4.

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.

Second TURB, restaging TURB or repeat TURB in primary T1 non-muscle invasive bladder cancer: impact on prognosis?

PURPOSE: A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. METHODS: Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. RESULTS: Median follow-up was 45.3 (IQR 22.7-81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). CONCLUSION: Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB.

Prognosis of Primary Papillary Ta Grade 3 Bladder Cancer in the Non-muscle-invasive Spectrum.

BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. OBJECTIVE: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta-T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. RESULTS AND LIMITATIONS: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomitant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought. PATIENT SUMMARY: We used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought.

Long-term device survival after a first implantation of AMS800™ for stress urinary incontinence: Comparison between men and women.

PURPOSE: The artificial urinary sphincter is the reference treatment for stress urinary incontinence in men, but it remains rarely used in women. This study aimed to compare long-term device survival between women and men, after the first implantation of an AMS800™ artificial urinary sphincter (Boston Scientific) for the treatment of a non-neurogenic stress urinary incontinence. MATERIALS AND METHODS: This retrospective cohort study included all patients with nonneurogenic stress urinary incontinence who underwent surgery in a large-volume university hospital between 2000 and 2013. The primary outcome was the overall survival of the device, defined as the absence of any repeated surgery (revision or explantation) during follow-up. Men and women were matched 3:1 according to age and year of implantation. Differences were analyzed using a Cox model accounting for matching and applying time intervals because hazards were not proportional over time. Sensitivity analyzes were performed, excluding firstly a population with a history of radiotherapy and secondly a population with more than one previous surgery for urinary incontinence. RESULTS: A total of 107 women were matched to 316 men. Median follow-up was 6.0 years (Q1-Q3 1.8-9.4): 7.0 years (Q1-Q3 3.1-10.3) for women and 5.1 years (Q1-Q3 1.3-9.1) for men. During the follow-up, 56 patients had an explantation of the device: 44 men (13.9%) and 12 women (11.2%), and 113 had a revision: 85 men (26.9%) and 28 women (26.1%). Men have a significantly higher risk of explantation or revision than women between 6 months and 8 years after implantation (hazard ratio 2.12 [1.29-3.48]). Before 6 months and after 8 years, there were no significant differences. Both sensitivity analyses found consistent results. CONCLUSIONS: This study suggests that device survival seems better in women after the first 6 months.

T1G1 Bladder Cancer: Prognosis for this Rare Pathological Diagnosis Within the Non-muscle-invasive Bladder Cancer Spectrum.

BACKGROUND: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. OBJECTIVE: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. RESULTS AND LIMITATIONS: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. PATIENT SUMMARY: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer.

European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel.

BACKGROUND: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. OBJECTIVE: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. INTERVENTION: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. RESULTS AND LIMITATIONS: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review. CONCLUSIONS: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. PATIENT SUMMARY: The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule.

PD-L1 expression and pattern of immune cells in pre-treatment specimens are associated with disease-free survival for HR-NMIBC undergoing BCG treatment.

PURPOSE: To assess the association between PD-L1 expression and disease-free survival (DFS) in High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) patients treated with intravesical Bacillus Calmette-Guerin (BCG) instillations (IBI). METHODS: Retrospective study in five French centres between 2001 and 2015. Participants were 140 patients with histologically confirmed HR-NMIBC. All patients received induction and maintenance IBI. Pathological stage/grade, concomitant carcinoma in situ, lesion number and tumour size were recorded. CD3, CD8 and PD-L1 expression in tumour cells and in T cells in the tumour microenvironment (TME) was determined immunohistochemically. Median follow-up was 54.2 months. The primary outcome measure was DFS. Univariable and multivariable analyses were performed using the log rank test and Cox proportional hazards model. RESULTS: Of the 140 NMIBC, 52 (37.1%) were Ta, 88 (62.9%) were T1 and 100% were high grade. Median number of maintenance IBI was six (range 1-30). Twenty-five (17.9%) patients had recurrence/progression. In multivariable analysis, age (HR 1.07 [95% CI 1.02-1.13], p = 0.009), PD-L1 expression in tumour cells (HR per 10 units = 1.96 [95% CI 1.28-3.00], p = 0.02) and CD3/CD8 ratio (HR per 10 units = 3.38 [95% CI 1.61-7.11], p = 0.01) were significantly associated with DFS. However, using the cut-off corresponding for each PD-L1 antibodies, PD-L1 + status was not associated with DFS. CONCLUSION: Despite an association between PD-L1 expression and BCG failure in HR-NMIBC, the PD-L1 + status was not a prognostic factor in the response of BCG. Moreover, we confirmed the key role played by the IC within the microenvironment in BCG treatment. These findings highlighted the rationale to combine BCG and PD-L1/PD-1 antibodies in early bladder cancer.

Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?

BACKGROUND: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. OBJECTIVES: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. MATERIALS AND METHODS: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. RESULTS: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. CONCLUSIONS: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.

Robotic radical nephroureterectomy and segmental ureterectomy for upper tract urothelial carcinoma: a multi-institutional experience.

PURPOSE: To report a multi-institutional experience on robotic radical nephroureterectomy (RNU) and segmental ureterectomy (SU) for upper tract urothelial carcinoma (UTUC). METHODS: Data were prospectively collected from patients with non-metastatic UTUC undergoing robotic SU or RNU at three referral centers between 2015 and 2018. Transperitoneal, single-docking robotic RNU followed established principles. Bladder cuff excision (BCE) was performed with robotic or open approach. Techniques for SU included: ureteral resection and primary uretero-ureterostomy; partial pyelectomy and modified pyeloplasty; ureteral resection with BCE and direct- or psoas hitch-ureteroneocystostomy. We retrospectively evaluated the technical feasibility, and peri-operative and oncologic outcomes after robotic RNU/SU. RESULTS: 81 patients were included. No case required conversion to open surgery. Early major (Clavien-Dindo grade > 2) complications were reported in six (7.4%) patients (two after SU, four after RNU). Three patients experienced late major complications (one after SU, two after RNU). Median ΔeGFR at 3 months was - 1 ml/min/1.73 m2 after SU and - 15 ml/min/1.73 m2 after RNU. Positive surgical margins were recorded in five patients (one after SU, four after RNU). Median follow-up was 21 months and 22 months in the SU and RNU groups, respectively. Three (20%) patients had ipsilateral upper tract recurrence after SU, while five (7.5%) developed metastases after RNU. No case of port-site metastases or peritoneal carcinomatosis was reported. At last follow-up, 67 (82.7%) patients were alive without evidence of disease. CONCLUSION: Robotic SU and RNU are technically feasible and achieved promising peri-operative and oncologic outcomes in selected patients with non-metastatic UTUC.