Recommandations pour l’utilisation de la toxine botulinique de type A (Botox®) dans l’hyperactivité vésicale réfractaire idiopathique

RésuméObjectifsDéfinir des recommandations pour l’utilisation pratique de la toxine botulinique de type A (BoNTA) dans l’hyperactivité vésicale réfractaire idiopathique (HAVRI).MéthodeÉlaboration de recommandations de bonne pratique par consensus formalisé, validées par un groupe de 13 experts puis par un groupe de lecture indépendant.RésultatsEn cas d’infection urinaire celle-ci doit être traitée et l’injection reportée. Avant l’injection, il est recommandé de s’assurer de la faisabilité et de l’acceptabilité de l’auto-sondage. L’injection peut être réalisée après une anesthésie locale urétro-vésicale (lidocaïne), éventuellement complétée par l’inhalation de protoxyde d’azote et parfois sous anesthésie générale. L’injection sera réalisée au bloc opératoire ou en salle d’endoscopie. La vessie ne doit pas être trop remplie (risque de perforation). Le traitement doit être appliqué en 10 à 20 injections de 0,5 à 1mL réparties de manière homogène dans la vessie en restant à distance des méats urétéraux. Il n’est pas recommandé de laisser en place une sonde vésicale sauf en cas d’hématurie importante. Le patient doit être surveillé jusqu’à la reprise mictionnelle. Une note d’information sur les effets indésirables éventuels doit lui être remise à sa sortie. Une consultation doit être prévue 3 mois après la première injection (calendrier mictionnel, débitmétrie, résidu post-mictionnel et examen cytobactériologique des urines). Un résidu >200mL et/ou symptomatique doit faire discuter des auto-sondages. Une nouvelle injection pourra être envisagée lorsque le bénéfice clinique de la précédente s’estompe (entre 6 et 9 mois).ConclusionsLe respect de ces recommandations devrait permettre une utilisation optimale de la BoNTA.Niveau de preuve3.SummaryObjectivesProvide guidelines for practical usage of botulinum toxin type A (BoNTA) for refractory idiopathic Overactive Bladder management.Patients and methodsGuidelines using formalized consensus guidelines method. These guidelines have been validated by a group of 13 experts quoting proposals, subsequently reviewed by an independent group of experts.ResultsIn the case of patients with urinary tract infection, it must be treated and injection postponed. Before proposing an injection, it is recommended to ensure the feasibility and acceptability of self-catheterisation by patient. The injection can be performed after local anesthesia of the bladder and urethra (lidocaine), supplemented where necessary by nitrous oxide inhalation and sometimes under general anesthesia. Injection is performed in the operating room or endoscopy suite. The bladder should not be too filled (increased risk of perforation). Treatment should be applied in 10 to 20 injections of 0.5 to 1mL homogeneously distributed in the bladder at a distance from the urethral orifices. It is not recommended to leave a urinary catheter in place except in cases of severe hematuria. The patient should be monitored until resumption of micturition. After the first injection, an appointment must be scheduled within 3 months (micturition diary, uroflowmetry, measurement of residual urine and urine culture). Performance of self-catheterisation should be questioned in the case of a symptomatic post-void residual and/or a residue>200mL. A new injection may be considered when the clinical benefit of the previous injection diminishes (between 6 and 9 months). A period of three months must elapse between each injection.ConclusionsImplementation of these guidelines may promote best practice usage of BoNTA with optimal risk/benefit ratio

Neoadjuvant immunotherapy for muscle-invasive bladder cancer

Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadju-vant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint in-hibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: “bladder cancer” OR “urothelial carcinoma”, AND “neoadjuvant immunotherapy” OR “preoperative im-munotherapy”. We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer—4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer

Immune checkpoint inhibition in upper tract urothelial carcinoma

Introduction: Immunotherapy is changing the way we think about and treat urothelial carcinoma (UC). The PD-1/PD-L1 pathway inhibition has shown robust efficacy, associated with an acceptable toxicity profile, in patients with locally advanced and metastatic unresectable disease, addressing a high decades-old unmet medical need. Material and methods: Using the Pubmed database, we conducted a literature review for English written published articles up to June 2020. The highest available evidence for the immunotherapy treatment of UC with ICIs were evaluated. The leading phase one, two and three clinical trials were considered for inclusion (n = 12). Patient’s data were extracted from studies depicting the UTUC subpopulation. Results: Two monoclonal antibodies targeting PD-1 (pembrolizumab and nivolumab) and three to its ligand PD-L1 (atezolizumab, avelumab, and durvalumab) have obtained US FDA and EMA approval for the second-line treatment of platinum-pretreated patients, between 2016 and 2019. Atezolizumab and Pembrolizumab are even currently approved in the first-line setting for cisplatin ineligible patients, with PD-L1- positive tumor. The neoadjuvant scenario in localized high-risk disease is still evolving, with the first data available to date limited to the muscle-invasive bladder carcinoma. The management of patients with upper tract urothelial carcinoma (UTUC: renal pelvis and ureters) is complicated by the lack of specific high-level evidence, due to the rarity of the disease. No published studies addressing immunotherapy in UTUC patients only are available. The largest clinical trials aimed at UC patients, regardless of the upper or lower location of the primary tumor, have enrolled a minority of patients with UTUC, providing the data on which our current knowledge is based. However, targeted scientific efforts are needed to improve our level of care. Conclusions: This review summarizes the main currently available evidence on the use of the PD-1/PD-L1 pathway inhibition with reference to patients presenting with UTUC

Lymph Node Dissection During Radical Nephro-Ureterectomy for Upper Tract Urothelial Carcinoma: A Review

Although lymphonodal dissection is well-accepted for muscle-invasive bladder cancer management, its role is still debated during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). The aim of this study was to summarize the current knowledge concerning the indication, anatomical template, prognostic, and therapeutic roles of lymph node dissection (LND) performed at the time of RNU. Quality control markers, such as the number of lymph nodes (LN) removed, lymph node density, and safety of the different surgical approaches, were assessed. We performed a narrative review using the PubMed and ClinicalTrials.gov databases. We identified and analyzed articles based on the practice and the role of lymph node dissection for non-metastatic UTUC. There are no clear guidelines regarding the indication of LND for UTUC, but aggressive tumors may beneficiate from lymphadenectomy since lymph node invasion is a clear independent poor prognostic factor, allowing for adjuvant treatments. It seems that an extended lymphadenectomy may provide therapeutic advantages as a higher number of nodes removed may be related to the removal of undetected LNs micrometastases and a subsequent improvement in recurrence rate and cancer-specific survival. Clear anatomical templates are thus needed based on the location and the laterality of the primary tumor