[Pathological pelvic lymph node involvement in muscle-invasive bladder cancer patients treated with radical cystectomy: A narrative review]. / Envahissement ganglionnaire pelvien anatomopathologique après cystectomie totale pour le traitement des tumeurs de vessie infiltrant le muscle : une revue narrative de la littérature.

OBJECTIVE: To perform a narrative review of the contemporary literature on the diagnosis, prognosis and adjuvant management of muscle-invasive bladder cancer (MIBC) patients with pathological pelvic lymph node involvement (pN+) at radical cystectomy. METHOD: A narrative review of the contemporary literature available on Medline was conducted to report studies evaluating the diagnosis, prognosis and/or adjuvant treatments for MIBC patients with pN+ disease at radical cystectomy. RESULTS: Open or robotic extended pelvic lymph node dissection up to the crossing of the ureter with common iliac vessels can enhance the diagnosis of pN+ MIBC, especially using separate packages for the submission of a maximum number of lymph nodes. The main prognosis factors for pN+ patients are the number of positive and retrieved lymph nodes, lymph node density, extranodal extension as well as lymph node metastasis diameter. Adjuvant chemotherapy is likely to prolong overall survival in pN+ patients treated with radical cystectomy alone while adjuvant immunotherapy using nivolumab has been shown to decrease the risk of recurrence in all pN+ patients, especially those with ypN+ disease after neoadjuvant chemotherapy followed by radical cystectomy. However, few data are currently available on the role of adjuvant radiation therapy, which remains currently experimental for these patients. CONCLUSION: Multiple parameters have been reported to impact the diagnosis and prognosis of patients with pN+ MIBC at radical cystectomy. Adjuvant management is currently based on chemotherapy and immunotherapy with preliminary data on radiation therapy.

French AFU Cancer Committee Guidelines - Update 2022-2024: Non-muscle-invasive bladder cancer (NMIBC).

OBJECTIVE: To update the ccAFU recommendations for the management of bladder tumours that do not infiltrate the bladder muscle (NBMIC). METHODS: A systematic review (Medline) of the literature from 2020 to 2022 was performed, taking account of the diagnosis, treatment options and surveillance of NMIBC, while evaluating the references with their levels of evidence. RESULTS: The diagnosis of NMIBC (Ta, T1, CIS) is made after complete full-thickness tumour resection. The use of bladder fluorescence and the indication of a second look (4-6 weeks) help to improve the initial diagnosis. The EORTC score is used to assess the risk of recurrence and/or tumour progression. Through the stratification of patients in low, intermediate and high-risk categories, adjuvant treatment can be proposed: intravesical chemotherapy (immediate postoperative, initiation regimen) or BCG (initiation and maintenance regimen) instillations, or even the indication of cystectomy for BCG-resistant patients. CONCLUSION: Updating the ccAFU recommendations should contribute to improving patient management, as well as the diagnosis and treatment of NMIBC.

French AFU Cancer Committee Guidelines - Update 2022-2024: Muscle-Invasive Bladder Cancer (MIBC).

OBJECTIVE: To update the CCAFU recommendations for the management of muscle invasive bladder carcinoma (MIBC). METHODS: A systematic review (Medline) of the literature from 2020 to 2022 was performed taking account of the diagnosis, treatment options and surveillance of NMIBC and MIBC, while evaluating the references with their levels of evidence. RESULTS: MIBC is diagnosed after the most complete tumour resection possible. MIBC grading is based on CTU along with chest CT. Multiparametric pelvic MRI could be an alternative. Cystectomy with extensive lymphadenectomy is the gold standard treatment for non-metastatic MIBC. It should be preceded by platinum-based neoadjuvant chemotherapy in patients in good general health with satisfactory renal function. Enterocystoplasty is proposed in men and women in the absence of contraindications and when the urethral resection is negative on extemporaneous examination. Otherwise, transileal cutaneous ureterostomy is the recommended method of urinary diversion. Inclusion of all patients in an ERAS (Enhanced Recovery After Surgery) protocol is recommended. For metastatic MIBC, first line treatment with platinum-based chemotherapy (GC or MVAC) is recommended, if general health (PS>1) and renal function (clearance>60mL/min) so allow (only 50% of the cases). Pembrolizumab immunotherapy has demonstrated an overall survival benefit in second-line treatment. CONCLUSION: Updating the ccAFU recommendations should contribute to improving patient management, as well as the diagnosis and decision-making concerning MIBC treatment.

French AFU Cancer Committee Guidelines - Update 2022-2024: Upper urinary tract urothelial cancer (UTUC).

INTRODUCTION: The aim was to propose an update of the French Urology Association Cancer Committee (ccAFU) Recommendations on the management of upper urinary tract urothelial carcinomas (UUT-UC). METHODS: A systematic Medline search was performed between 2020 and 2022, taking account of the diagnosis, treatment options and follow-up of UUT-UC, while evaluating the references with their levels of evidence. RESULTS: The diagnosis of this rare pathology is based on CTU acquisition during excretion and flexible ureterorenoscopy with histological biopsies. Radical nephroureterectomy (RNU) remains the gold standard for surgical treatment. Nevertheless conservative treatment can be discussed for low risk lesions: tumour of low-grade, with no infiltration on imaging, unifocal<2cm, eligible for full treatment therefore requiring close endoscopic surveillance by flexible ureteroscopy in compliant patients. After RNU, postoperative instillation of chemotherapy is recommended to reduce the risk of recurrence in the bladder. Adjuvant chemotherapy has shown clinical benefits compared to surveillance after RNU for tumours (pT2-T4 N0-3 M0). CONCLUSION: These updated recommendations should contribute to improving not only patients' level of care, but also the diagnosis and decision-making concerning treatment for UUT-UC.

Biochemical relapse predictive factors in patients with lymph node metastases during radical prostatectomy.

INTRODUCTION: There are no clear recommendations for the management of patients with lymph node invasion discovered during radical prostatectomy for prostate cancer (PCa). Adequate risk stratification could personalize post-surgical adjuvant treatment. Our objective was to identify predictive factors for biochemical relapse (BCR) in patients with lymph node (LN) invasion at the time of radical prostatectomy(RP). MATERIALS AND METHODS: Patients who underwent RP for high-risk PCa with LN invasion in two academic centres between 2008 and 2019 were included. Patients with metastatic disease or extrapelvic LN involvement were excluded. Following data were collected retrospectively: age, preoperative prostate-specific antigen level, Gleason score, clinical and pathological stage, number of metastatic LN and LN density. Outcome was BCR during follow-up. BCR-free survival was assessed by Kaplan-Meier method and its association with relevant variables was determined with log-rank test. RESULTS: Twenty-six patients were included. Median (IQR) age, PSA and follow-up were 64.5 years (55-78), 9.2ng/mL (4.4-20) and 16.1 months (6-27.5), respectively. Twenty patients (77%) had BCR after surgery, accounting for 24-month BCR-free survival of 65%. Patients with LN density > 15% had better survival rates than those with ≤ 15% (40% vs. 0%, respectively, at 24 months; P=0.06) without reaching significance. Cox proportional Hazards analysis could not evidence predictive factors of BCR free-survival. CONCLUSIONS: LN density seemed associated with BCR-free survival within patients with high-risk PCa and positive LN at RP. However, extraprostatic extension, number of positive LN and positive surgical margins were not independent risk factors for BCR. Larger prospective studies with centralized pathological reviews are needed. LEVEL OF PROOF: 3.

[Guidelines from the cancer (CC-AFU) and infection disease (CI-AFU) committees of the French Association of Urology for the management of adverse events and complications of BCG]. / Recommandations des Comités de cancérologie (CC-AFU) et d'infectiologie (CI-AFU) de l'Association française d'urologie pour la prise en charge effets indésirables et complications du BCG.

INTRODUCTION: Intravesical instillations of BCG are recommended for the treatment of high-risk non-muscle-invasive bladder cancer. However, their prolonged use remains limited by the associated potentially serious adverse effects or complications. The purpose of this article was to provide updated recommendations for the diagnosis and management of adverse events (AEs) or complications of intravesical BCG instillations. MATERIALS AND METHODS: Review of the literature in Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using the following MeSH keywords or a combination of these keywords: "bladder," "BCG," "complication," "toxicity," "adverse events," "prevention," and "treatment". RESULTS: AEs or complications of BCG included genitourinary and systemic symptoms. The most common complications (cystitis, moderate fever) should be treated symptomatically and may require adjustment to allow patients to have the most complete BCG treatment possible. Serious complications are rare but must be identified promptly because of the life-threatening nature of the disease. Their management is based on the combination of anti-tuberculosis treatments, anti-inflammatory drugs and the definitive discontinuation of BCG. CONCLUSION: The management of BCG AEs requires early identification, rational and effective treatment if necessary, and discussion of the continuation of treatment for each situation.

[Guidelines from the cancer committee of the French Association of Urology (CC-AFU) for adequate intravesical instillations of Mitomycin C, Epirubicin, and BCG for non-muscle invasive bladder cancer]. / Recommandations du Comité de cancérologie de l'Association Française d'Urologie (CC-AFU) pour la bonne pratique des instillations intravésicales de mitomycine C, d'épirubicine et de BCG pour le traitement des tumeurs de la vessie n'infiltrant pas le muscle (TVNIM).

INTRODUCTION: Intravesical instillations of mitomycin C, epirubicin and BCG are considered as the standard treatment for most patients diagnosed with non-muscle invasive bladder cancer. These guidelines aim to optimize the adjuvant intravesical treatment in order to increase the efficacy and lower the morbidity associated with its administration. METHODS: We conducted a daily practice survey, an online search of available national regulation recommendations and of published guidelines. A bibliography search in French and English using Medline® and Embase® with the keywords "BCG"; "mitomycin C"; "epirubicin"; "bladder"; "complication"; "toxicity"; "adverse reaction"; "prevention" and "treatment" was performed November 2021. RESULTS: Patient information should be given by the attending physician before the first intravesical instillation. A medical exam to look for specific contraindications is also mandatory to select adequate candidates. Intravesical instillations should be delivered in health-care centers where urologic endoscopic procedures are routinely performed. Attending urologist or specialized nurse should check for negative pretreatment urine test. Intravesical instillation can only be delivered after bladder catheter has been inserted in the bladder without any injury of the lower urinary tract. The pharmaceutical agent should be kept in the bladder for two hours. Finally, voiding within the 6hours following intravesical instillations should be done in the sitting position and the patient should drink at least 2 liters of water per day for 2 days. CONCLUSION: The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity.

[Prognostic value of PD-1/PD-L1 expression in upper tract urothelial carcinoma]. / Intérêt pronostique de l'expression de PD-1/PD-L1 dans les tumeurs de la voie excrétrice urinaire supérieure.

Current literature supports the efficacy of anti-PD-1 and anti-PD-L1 immune checkpoint inhibitors for the treatment of urothelial carcinomas. While the prognostic value of PD-1 and PD-L1 levels has been comprehensively analyzed for urothelial carcinoma of the bladder, less is known for upper tract urothelial carcinoma. In addition, available data on the prognostic value of PD-1 and/or PD-L1 level in the tumor and/or peritumoral microenvironment are heterogeneous and even sometimes contradictory. In this article, we compared the methodologies of the various available studies in order to highlight the factors that can explain these discordant results.

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

BACKGROUND: We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). METHODS: Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. RESULTS: Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). CONCLUSIONS: We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

[Local analgesia during flexible cystoscopy in male patients: A non-inferiority study comparing Xylocaine® gel to Instillagel® Lido]. / Anesthésie locale pour fibroscopie chez l'homme : étude de non-infériorité comparant le Xylocaine® gel à l'Instillagel® Lido.

INTRODUCTION: Local anesthesia using urethral gel has been proven to reduce discomfort of male patients during flexible cystoscopy. This study was a non-inferiority study between two lidocain-containing urethral gel (Instillagel® Lido and Xylocaine® gel). METHODS: A prospective single center study was conducted between June 2014 and November 2014. Male patients seen in the office and in whom a flexible cystoscopy was planned were included in the present study and received urethral instillation of either Xylocaine® gel or Instillagel® Lido at least 5minutes before flexible cystoscopy. No other anesthetic agent was used. Primary endpoint was pain during the procedure, assessed through visual analog scale (VAS) from 0 to 10. RESULTS: Four hundred and sixty-one men were included: 233 in the Instillagel® Lido group and 228 in the Xylocaine® gel group. Indications of flexible cystoscopy non-muscle invasive bladder cancer follow-up in 44 % of cases, hematuria work-up in 21 % of cases and lower urinary tract symptoms work-up in 35 %. Patients' age was comparable betwwen both groups: 64.5 years (±1.1) in the Instillagel® Lido group and 66.2 years (±1.1) in the Xylocaine® gel group (P=0.29). The mean VAS was 0.8 (±0.1) in the Instillagel® Lido group and 0.6 (±0.1) in the Xylocaine® gel group (P=0.10). The non-inferiority criterion was reached (P<0.001) as the average difference in VAS between the two groups was 0.2 with a confidence interval not comprising 1 (CI 97.5 %: -0.47; 0.07). CONCLUSION: In this prospective study, Instillagel® Lido was not inferior to Xylocaine® gel for local analgesia during flexible cystoscopy in male patients. LEVEL OF EVIDENCE: 4.

A systematic review and meta-analysis of oncological and renal function outcomes obtained after segmental ureterectomy versus radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVE: To perform a systematic review and meta-analysis of the comparative studies reporting oncological and renal function outcomes of segmental ureterectomy (SU) versus radical nephroureterectomy (RNU) for upper tract urothelial carcinomas (UTUC). MATERIALS AND METHODS: A literature search on Pubmed, Embase, and the Cochrane library was conducted according to the PRISMA guidelines, and a meta-analysis was performed to assess cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS), intravesical recurrence free survival (IVRFS) and surgery-related variations in estimated glomerular filtration rate (eGFR). RESULTS: A total of 11 retrospective studies with 3963 patients who underwent either SU (n = 983; 24.8%) or RNU (n = 2980; 75.2%) were included. Although patients treated with SU were more likely to be diagnosed with favorable pathological features, the meta-analysis of unadjusted data revealed no significant difference between both groups in terms of CSS (HR 0.90, p = 0.33) and OS (HR 0.98, p = 0.93). Accordingly, the meta-analysis of adjusted data confirmed equivalent CSS (HR = 0.90, p = 0.47) between SU and RNU. Similarly, no significant difference was found in terms of RFS (HR 1.06, p = 0.72) and IVRFS (HR 1.35, p = 0.39). However, a significant decreased risk of impaired renal function was observed after SU when compared to RNU (mean eGFR difference = 9.32 ml/1.73 m2, p = 0.007). CONCLUSION: Although adverse patient and tumor characteristics were not equally balanced between treatment arms, our systematic review and meta-analysis supports similar oncological outcomes between SU and RNU, with better preservation of renal function after SU. As such, SU should be preferably used as the first-line treatment for low-risk ureter tumors, while considered for selected cases of high-risk disease.

45 or 50 Gy, Which is the Optimal Radiotherapy Pelvic Dose in Locally Advanced Cervical Cancer in the Perspective of Reaching Magnetic Resonance Image-guided Adaptive Brachytherapy Planning Aims?

AIMS: In locally advanced cervical cancer, the dose delivered results from the sum of external beam radiotherapy and brachytherapy, and is limited by the surrounding organs at risk. The balance between both techniques influences the total dose delivered to the high-risk clinical target volume (HR-CTV). The aim of the present study was to compare the ability of reaching different planning aims after external beam radiotherapy pelvic doses of 45 Gy in 25 fractions or 50.4 Gy in 28 fractions, both considered as standard prescriptions. MATERIALS AND METHODS: The optimised plans of 120 patients treated with pelvic chemoradiation followed by magnetic resonance image-guided intracavitary brachytherapy were reviewed. The doses per pulse were calculated, and the number of pulses required to reach the planning aims, or a limiting dose constraint to organs at risk, was calculated. All doses were converted to 2-Gy equivalents. Three scenarios were applied consisting of different sets of planning aims: 85 and 60 Gy for the HR-CTV and the intermediate-risk CTV (IR-CTV) D90 (minimal dose received by 90% of the volume) in scenario 1, 90 and 60 Gy, respectively, for scenarios 2 and 3. For organs at risk, dose constraints were 90, 75 and 75 Gy to the bladder, rectum and sigmoid D2cm(3), respectively, in scenarios 1 and 2, and 80, 65 and 70 Gy in scenario 3. RESULTS: A similar HR-CTV D90 could have been reached in scenarios 1 and 2 according to both pelvic doses. In scenario 3, a higher mean HR-CTV could have been reached in the 45 Gy arm (83.5 ± 8.0 versus 82.4 ± 8.0, P < 0.0001). The mean D2cm(3) of organs at risk was systematically and significantly increased after a delivery of 50.4 Gy to the pelvis, from 0.9 to 2.89 Gy. The proportions of plans reaching planning aims were 85.8, 72.5 and 42.5% after 45 Gy and 85.5, 67.5 and 33.3% after 50.4 Gy according to scenarios 1, 2 and 3, respectively. According to scenario 3, 50.4 Gy, the reachable HR-CTV D90 was higher in 30% of the cases, by 2 Gy in two cases. Those cases were unpredictable and due to unfavourable organs at risk topography and poor response to external beam radiotherapy. CONCLUSION: The delivery of 45 Gy in 25 fractions to the pelvis before brachytherapy warrants a higher probability to reach brachytherapy planning aims, in comparison with 50.4 Gy in 28 fractions.

[French resident's performance on laparoscopic surgery box trainer: 7-year results of pelvitrainer contests]. / Performance des internes français sur simulateur de chirurgie laparoscopique : les résultats de 7 ans d'olympiades du pelvitrainer.

OBJECTIVES: The study objectives were to analyze the resident's laparoscopic surgery performance in order to build a self-assessment data set, to identify discriminatory exercises and to investigate the suturing time changes. METHODS: From 2007 to 2014, the French Association of Urologist in Training (AFUF) organized 7 pelvitrainer contests. Participant scores on 11 laparoscopic surgery exercises were evaluated. RESULTS: Sixty-six residents participated to these contests and performed 11 exercises each. Twenty-two (33.3 %) participants were beginners, 26 (39.4 %) intermediates et 18 (27.3 %) experienced. The participant scores were gathered into a data set including the average time per exercise. We found a time scoring improvement related to the resident experience for all exercises. A significant decline in time was noted for exercise 8 and 9 between beginners and intermediates (139s [±71]), (173.9s [±118.3]) and between beginners and experienced (80.6s [±26.7]), (94,1s [±42.7]) with a P<0.05. The correlation coefficient for the exercise 11 duration (vesico-uretral anastomosis) was 0.04 over a 7-year period (P=0.44). CONCLUSION: The study provided a data set on 11 laparoscopic surgery tasks which can be consulted by all residents as a reference in a self-assessment process. Two exercises (8 and 9) discriminated beginners from intermediates and experienced groups and could be used as a benchmark ahead of an operating room procedure. The vesico-uretral anastomosis duration (exercise 11) did not improve significantly between 2006 and 2014. LEVEL OF EVIDENCE: 4.