First-Line Sequential Gemcitabine and Docetaxel Treatment for High-Risk Non-Muscle Invasive Bladder Cancer - Expert Commentary

The administration of bacillus Calmette-Guérin (BCG) as an adjuvant is recommended in the context of high-risk non-muscle invasive bladder cancer (NMIBC) after complete transurethral resection of bladder tumor (TURBT). However, there have been production shortages of BCG. Moreover, efficacy is suboptimal and clinical tolerance of BCG has been problematic.

Accordingly, there have been various efforts to identify alternative intravesical therapies for high-risk NMIBC in the context of first-line or salvage treatment. Sequential intravesical gemcitabine and docetaxel have been reported to be efficacious and well-tolerated in NMIBC patients who did not respond to BCG treatment. McElree et al. investigated clinical outcomes in patients with high-risk NMIBC who were BCG-naïve and received gemcitabine and docetaxel as first-line therapy.

They investigated a cohort of 107 high-risk NMIBC patients. The median follow-up among patients was 15 months, and 17.8% of patients experienced bladder cancer recurrence during this period. At 6, 12, and 24 months, 89%, 85%, and 82% of patients exhibited relapse-free survival, respectively. Overall survival was 84% at 24 months. None of the patients in the study cohort developed metastatic disease or died of NMIBC during the study period. During treatment, 56% of patients had at least one adverse event, and 3.7% did not complete the treatment course due to intolerance (hematuria, nocturia). Out of the 92 adverse events, 31 were grade 1, 60 were grade 2, and 1 was grade 3. The most commonly reported side effect was urinary frequency or urgency. Other common side effects included hematuria and dysuria.

Overall, the survival rates among patients treated with gemcitabine and docetaxel were comparable to those in patients treated with BCG. The results of this study are highly promising, particularly the absence of progressive disease among patients who were considered high-risk. Furthermore, the combination treatment was very well-tolerated, and most patients completed the full treatment course. Nevertheless, the authors reported selection bias and confounding factors due to the retrospective design of the study. One key limitation is the lack of a control group to which outcomes were compared.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine


  1. McElree IM, Steinberg RL, Martin AC, et al. Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer. J Urol. 2022;208(3):589-599. doi:10.1097/JU.0000000000002740

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