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Detrimental effect of delayed or incomplete BCG protocols administration after trans-urethral tumor resection in patients with non-muscle-invasive bladder cancer: a systematic review.

Minerva urology and nephrology2026 Apr

Ettore DI Trapani, Arturo Lo Giudice, Elio Mazzone, Paolo Dell'oglio, Gabriele Sorce, Stefano Luzzago, Francesco A Mistretta, Giovanni LA Croce, Mattia Piccinelli, Dario DI Trapani, Marco Moschini, Antonio Galfano, Francesco Montorsi, Alberto Briganti, Firas Abdollah, Ottavio DE Cobelli, Gennaro Musi

Abstract

INTRODUCTION: Bacillus Calmette-Guérin (BCG) immunotherapy remains the standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC). While the European Association of Urology (EAU) guidelines recommend initiating BCG treatment no later than 4-6 weeks following transurethral resection of bladder tumors (TURBT), delays in BCG administration are not uncommon due to factors such as pathological assessment timelines, patient-related issues, healthcare system limitations, and drug shortages. This systematic review aims to evaluate the impact of delayed BCG therapy or unconventional schedules on oncological outcomes, trying to establish the best treatment option for these patients. EVIDENCE ACQUISITION: A comprehensive literature search was conducted across multiple databases (PubMed, Scopus, Web of Science) for studies published from January 2010 to the present. After screening 262 publications, relevant prospective and retrospective studies, systematic reviews, and meta-analyses were included. EVIDENCE SYNTHESIS: We retrieved 14 manuscripts evaluating different BCG schedule or doses. Only two papers specifically referred to the delay in the treatment of high risk NMIBC. The findings highlight that the delays in initiating the BCG therapy beyond 6 weeks are associated with worse recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS) rates. However, evidence on the progression to MIBC or metastatic disease remains inconclusive, with only a few studies suggesting a potential impact. Despite these delays, even reduced dose or shortened BCG regimens appear to offer some level of protection against disease progression. CONCLUSIONS: This review emphasizes the importance of adhering to standard BCG treatment schedules to minimize the risk of recurrence and suggests that, in cases of unavoidable delay, strict endoscopic follow-up is crucial and an optimal treatment in case of cancer relapse must be offered. Further prospective studies are needed to conclusively determine the long-term effects of delayed therapy.

Keywords

HumansUrinary Bladder NeoplasmsBCG VaccineAdjuvants, ImmunologicNeoplasm InvasivenessCystectomyAdministration, IntravesicalTime FactorsUrethraDrug Administration ScheduleNon-Muscle Invasive Bladder Neoplasms

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