ABSTRACT
Introduction & Objectives: Patients with high risk non muscle invasive bladder cancer (NMIBC) who experience BCG failure have limited bladder preserving treatment options as radical cystectomy currently represents the standard therapeutical approach. Systematic immunotherapy (IO) has changed the landscape in advanced bladder cancer and is currently being investigated in NMIBC. Based on the hypothesis that intravesical administration will not be related with severe adverse events, we evaluated the role of intravesically administered durvalumab in NMIBC patients after BCG failure. Material(s) and Method(s): An open label, single-arm, multi-center, phase II clinical trial was conducted. A run-in phase had the objective to determine the maximum tolerated dose (MTD) of durvalumab and to exclude a detrimental effect on disease relapse by this strategy. Durvalumab was administered for a total of 6 instillations per patient at consecutive levels of 500, 750 and 1000 mg. Phase II has as primary end point the 1-year high-grade-relapse-free (HGRF)-rate. Secondary endpoints included toxicity, and high-grade progression-free rat at 1, 3 and 6 months after treatment. Result(s): Thirty patients were enrolled (run in phase: 9, phase II: 21). One patient withdrew consent prior to receiving study treatment, so 29 patients were included in efficacy and toxicity analyses. Mean age was 66.5 years. MTD of durvalumab was set at 1000 mg as no dose related toxicities (DLTs) occurred at any level studied. Three of 9 patients included in the run-in phase (33.3%) were tumor free one month after the last durvalumab instillation, therefore, the null hypothesis was rejected by the futility analysis. Western blot showed that durvalumab remained stable in urine during instillation. One patient died from Covid-19, 3 months after the last durvalumab administration. All patients concluded at least 1 year follow up. One-year HGRF rate was 34.6%. HGRF rates at 1, 3 and 6 months was 73%, 65.3% and 50% respectively. Five patients (17%) experienced a T2 or above disease relapse. Five out of the six patients who received 500mg or 750mg of durvalumab relapsed within 1 year. When efficacy analyses were restricted to patients receiving 1000mg of durvalumab, 1-year HGRF rate was 35%. Interestingly, 2 out of 2 patients with only CIS disease at baseline experienced a tumor complete response, which was durable and was maintained at least for a year. No severe adverse events were noted. The most common adverse event was Grade 1 hematuria. Conclusion(s): Intravesical IO using durvalumab was proved to be feasible with an excellent safety profile. Oncological results seem to be promising and comparable with other bladder preserving strategies in BCG failure with the advantage of a better safety profile. Further study of intravesical IO in high-risk patients with NMIBC after BCG failure is warranted.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.
ABSTRACT
Introduction & Objectives: On March 11, 2020, WHO declared Covid-19 as a pandemic placing a significant strain on the worldwide healthcare system. Although urology does not stand at the frontline of care for patients with Covid-19, every practicing urologist has been affected by the global outbreak. The objective of this review is to evaluate the impact of Covid-19 pandemic on urology residency training programs. Materials & Methods: We performed a literature review of the current evidence on urology residency training during the Covid-19 pandemic. Relevant databases (MEDLINE, Scopus, Cochrane Library) were searched (until June 2021) and the main study-inclusion criterion was the presence of residents’ or directors’ opinion on their residency training program during the Covid-19 crisis. Results: Literature search identified 72 articles. 14 studies comprising a total of more than 2500 residents were eligible for inclusion in the analysis. During the pandemic, learning activities carried out by urology residents suffered a forced modulation. There has been a decrease in operation volume especially in procedures in which residents were directly involved. Similarly, there was a decline in most of the academic activities worldwide. Furthermore, the negative impact on residents’ mental well-being and lifestyle is reported by many studies. On the other hand, the lockdown stressed the opportunity to review the current training system and to increase the implementation of tools such as telemedicine and smart-learning surgical skill training programs. Conclusions: Covid-19 pandemic has resulted in significant changes in urology residency programs worldwide, with a negative impact on matters such as surgical training and academic activities. Residents’ well-being and mental health is also risked. Hopefully, this unprecedented situation has generated new online learning modalities and technological innovations in the field of training in urology