Role of sequential intravesical gemcitabine plus docetaxel in refractory/recurrent non-muscle invasive urinary bladder cancer following intravesical BCG: an updated systematic review

Bacillus Calmette–Guérin (BCG) immunotherapy is the cornerstone of adjuvant management for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). However, 30–40% of patients exhibit BCG-unresponsive disease, for which radical cystectomy remains the standard but is often declined due to morbidity and quality-of-life implications. Sequential intravesical gemcitabine plus docetaxel (Gem/Doce) has emerged as a pragmatic bladder-preserving alternative, but evidence remains heterogeneous. To systematically evaluate oncological outcomes and safety of sequential intravesical Gem/Doce in patients with BCG-refractory or recurrent NMIBC. A comprehensive search of PubMed, Science Direct, Medline, Embase, and Scopus (January 2009–October 2025) identified studies reporting Gem/Doce outcomes in BCG-unresponsive NMIBC. Eligible studies were original clinical studies reported in English. Risk of bias was assessed using design-specific Joanna Briggs Institute critical appraisal tools. Given the clinical and outcome heterogeneity across studies, findings were synthesized narratively and no quantitative meta-analysis was performed. This review was registered with PROSPERO (CRD42024609822) and followed PRISMA guidelines. Of 521 retrieved articles, 12 met the inclusion criteria encompassing 1,248 patients. One-year recurrence-free survival (RFS) ranged 50–65% (high-grade RFS 60–65%), with two-year RFS 34–46% (high-grade RFS 30–52%). Five-year progression-free survival exceeded 80%, and bladder-preservation and cancer-specific survival approached 75% and 91%, respectively. Discontinuation for toxicity was < 5%, with predominantly Grade 1–2 urinary symptoms. Comparative analyses showed Gem/Doce achieved outcomes similar to repeat BCG, with potential improvements in progression-free and cystectomy-free survival. Sequential intravesical gemcitabine plus docetaxel seems to offer reproducible oncologic control and excellent tolerability in BCG-unresponsive NMIBC, supporting its role as an accessible salvage regimen when cystectomy is deferred. Nevertheless, evidence remains largely retrospective and short-term. Future prospective, large multicentre randomised trials with longer follow-up are essential to confirm durability, comparative effectiveness and its position within contemporary bladder-preserving algorithms.