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Background: The European Association of Urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus Calmette-Guérin (BCG) treatment remains controversial., Objective: To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG., Design, Setting, and Participants: A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted., Outcome Measurements and Statistical Analysis: A survival analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), and the cumulative incidence of cancer-specific mortality (CSM) after accounting for other causes of mortality as competing risk events and of the overall mortality (OM). Conditional survival probabilities for 0-4 yr without events were computed. Cox regression assessed the predictors of oncological outcomes., Results and Limitation: A total of 640 patients, with a median 47 (32-67) mo follow-up for event-free individuals, were analyzed. High-grade RFS and PFS at 5 yr were 53% (49-57%) and 78% (74-82%), respectively. The cumulative incidence of CSM and OM at 5 yr was 13% (10-16%) and 16% (13-19%), respectively. Conditional RFS, PFS, overall survival, and cancer-specific survival at 4 yr were 91%, 96%, 87%, and 94%, respectively. Cox regression identified tumor grade (hazard ratio [HR]: 1.54; 1.1-2) and size (HR: 1.3; 1.1-1.7) as RFS predictors. Tumor multiplicity predicted RFS (HR: 1.6; 1.3-2), PFS (HR: 2; 1.2-3.3), and CSM (HR: 2; 1.2-3.2), while age predicted OM (HR: 1.48; 1.1-2)., Conclusions: Patients with VHR NMIBC who receive adequate BCG therapy have a more favorable prognosis than predicted by EAU risk groups, especially among those with a sustained response, in whom continuing maintenance therapy emerges as a viable alternative to radical cystectomy., Patient Summary: Our research shows that a sustained response to bacillus Calmette-Guérin in patients can lead to favorable outcomes, serving as a viable alternative to cystectomy for select cases., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aim: This review article summarizes the current clinical practice guidelines around disease definitions and risk stratifications, and the treatment of non-muscle-invasive bladder cancer (NMIBC). Recently completed and ongoing clinical trials of novel and investigational therapies in Bacillus Calmette-Guérin (BCG)-naïve, BCG-recurrent, and BCG-unresponsive patient populations are also described, e.g., those involving immune checkpoint inhibitors, targeted therapies, other chemotherapy regimens, vaccines, and viral- or bacterial-based treatments. Finally, a brief overview of enhanced cystoscopy and drug delivery systems for the diagnosis and treatment of NMIBC is provided., Background: A global shortage of access to BCG is affecting the management of BCG-naïve and BCG-recurrent/unresponsive NMIBC; hence, there is an urgent need to assist patients and urologists to enhance the treatment of this disease., Methods: Searches of ClinicalTrials.gov, PubMed, and Google Scholar were conducted. Published guidance and conference proceedings from major congresses were reviewed., Conclusion: Treatment strategies for NMIBC are generally consistent across guidelines. Several novel therapies have demonstrated promising antitumor activity in clinical trials, including in high-risk or BCG-unresponsive disease. The detection, diagnosis, surveillance, and treatment of NMIBC have also been improved through enhanced disease detection., (Copyright © 2021 Pfizer Inc., the Author(s). Published by Elsevier Inc. All rights reserved.)

Since its introduction more than 40 years ago, adjuvant treatment with BCG (Bacillus Calmette-Guérin) for non-muscle invasive bladder cancer (NMIBC) continues to be the treatment recommended in the highrisk group, and one of the most successful immunotherapies for cancer treatment. However, up to 20% of patients will progress to muscle-invasive disease after BCG treatment. On the other hand, we are facing a shortage of BCG supply worldwide. Despite its extensive clinical use, there is no clear certainty of the mechanism of action of BCG, and controversy persists regarding to the most effective dose and strains, as well as their usefulness in combined treatments with other drugs and with devices that could facilitate their action on the bladder. This article historically reviews the impact that has had BCG in the treatment of NMIBC, the current guidelines in terms of doses, strains and treatments combination, and the future that will happen with the results of the ongoing clinical trials with systemic immunotherapy, vaccines and gene therapy.

Purpose of Review: The standard diagnosis of carcinoma in situ (CIS) of the bladder, based on white light cystoscopy and urine cytology, is limited because CIS can vary from normal-appearing mucosa to a lesion indistinguishable from an inflammatory process. Intravesical instillation of Bacillus Calmette-Guerin (BCG) remains first-line therapy; however, a significant proportion of cases persist or recur after BCG treatment. This review summarizes recent improvements in the detection and treatment of CIS., Recent Findings: The new optical technologies improve CIS detection, with a potential positive impact on oncological outcomes. The usefulness of MRI-photodynamic diagnosis fusion transurethral resection in CIS detection is unclear and further studies are needed. BCG instillation remains the first-line therapy in CIS patients and seems to improve recurrence and progression rates, especially with the use of maintenance. Intravesical device-assisted therapies could be effective in both BCG-naïve and BCG-unresponsive CIS patients, but further studies are ongoing to clarify their clinical benefit. A phase II clinical trial with pembrolizumab has shown the potential effectiveness of immune checkpoint inhibitors in BCG-unresponsive CIS patients and further trials are ongoing., Summary: New optical techniques increase the CIS detection rate. BCG instillation remains the first-line treatment. Immune checkpoint inhibitors could be a future alternative in BCG-naïve and BCG-unresponsive CIS patients.

Objective: To assess whether bacillus Calmette–Guérin (BCG) responsiveness after initiation of an adequate BCG treatment (at least five of six instillations of induction and at least two of three instillations of maintenance) impacts oncological outcomes in patients with carcinoma in situ (CIS) of the bladder treated with BCG immunotherapy. Patients and Methods: Data were available for 193 patients with bladder CIS with or without associated cTa/cT1 disease who received an adequate BCG treatment between 2008 and 2015. Bladder biopsies were taken at 6 months and patients were then stratified as either BCG responsive (negative biopsies) or BCG unresponsive (positive biopsies). Inverse probability weighting (IPW)‐adjusted Kaplan–Meier and IPW‐adjusted Cox regression were performed to compare progression‐free survival (PFS), radical cystectomy‐free survival (RCFS), overall survival OS, and cancer‐specific survival (CSS) in the two groups. Results and Limitations: Comparing the BCG‐responsive and BCG‐unresponsive groups, IPW‐adjusted Kaplan–Meier analysis revealed, respectively, a median (interquartile range) of PFS of 9 (5–15) vs 48.5 (28–77) months (P = 0.001), a RCFS of 11 (9–15) vs 49 (24–76) months (P < 0.001), and a CSS of 25 (13–60) vs 109 (78–307) months (P = 0.004). On IPW‐adjusted Cox regression analysis, BCG‐unresponsive patients had a worse PFS (hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.59–7.27), RCFS (HR 3.52, 95% CI 1.77–7), and CSS (HR 4.42, 95% CI 1.95–10.01). We found no significant differences for OS. Conclusion: Using an IPW method we found that lack of response after initiation of an adequate BCG treatment has prognostic implications beyond identification of complete response in patients with CIS. BCG‐unresponsive patients, satisfying the novel definition of BCG unresponsive, showed a poor PFS, RCFS, and CSS. In this setting, the patients should be counselled regarding RC as a first option or enrolled in a clinical trial if they refuse RC or are unfit for surgery. [ABSTRACT FROM AUTHOR]