Background: Non–muscle-invasive bladder cancer (NMIBC) accounts for the majority of newly diagnosed bladder cancer cases and is characterized by high rates of recurrence and progression. Intravesical Bacillus Calmette–Guérin (BCG) remains the standard of care for high-risk disease; however, treatment intolerance, failure, and global supply shortages have prompted investigation of alternative intravesical therapies. Objective: To summarize and critically appraise the existing clinical evidence evaluating sequential intravesical gemcitabine and docetaxel (Gem/Doce) in NMIBC, across different clinical contexts. Methods: We performed a narrative review of published clinical studies assessing sequential intravesical Gem/Doce in patients with BCG-unresponsive, BCG-exposed, and selected treatment-naïve NMIBC. Reported oncologic outcomes, including recurrence-free survival, progression, cystectomy rates, and treatment-related adverse events, were reviewed. Emerging exploratory approaches, including biomarker-based risk stratification, were also described. Results: Across multiple retrospective and prospective studies, Gem/Doce has demonstrates favorable recurrence-free survival, and acceptable safety profiles, particularly in patients with BCG-unresponsive or previously treated high-risk NMIBC. Reported rates of progression and cystectomy are generally low, and treatment discontinuation due to toxicity is uncommon. Exploratory studies have evaluated AI-assisted histologic biomarkers as potential tools for risk stratification and hypothesis-generating treatment selection; however, these approaches remain investigational and require prospective validation. Conclusion: Current evidence suggests that sequential intravesical Gem/Doce is a well-tolerated bladder-sparing option with encouraging oncologic outcomes, particularly in patients with recurrent or BCG-unresponsive NMIBC. While early data have explored its use in treatment-naïve settings, definitive conclusions regarding its role as first-line therapy require validation in prospective randomized trials. Keywords: urinary bladder neoplasms, gemcitabine, docetaxel, refractory, treatment failure, naïve, untreated
Ghavshough et al. (Thu,) studied this question.