Comparative effectiveness of intravesical gemcitabine vs. sequential gemcitabine and docetaxel for high-risk nonmuscle-invasive bladder cancer.

BACKGROUND

Sequential intravesical gemcitabine and docetaxel (Gem/Doce) are increasingly used for nonmuscle-invasive bladder cancer (NMIBC), especially in the setting of Bacillus Calmette-Guérin (BCG) shortage or failure. However, the contribution of docetaxel to gemcitabine remains unquantified. We compared the effectiveness of gemcitabine alone vs. Gem/Doce in high-risk NMIBC.

METHODS

We conducted a retrospective study of 296 patients treated with gemcitabine (n = 173) or Gem/Doce (n = 123) at 3 Mayo Clinic sites between 2018 and 2023. The primary outcome was high-grade recurrence-free survival (HGRFS). Secondary outcomes included recurrence-free, progression-free, cystectomy-free, cancer-specific, and overall survival and adverse events. Analyses included Kaplan-Meier and Cox regression with 2-stage residual inclusion to adjust for confounding.

RESULTS

Median HGRFS was similar between groups (gemcitabine: 22.6 months; Gem/Doce: 19.5 months [P = 0.25]). Among patients with BCG-unresponsive carcinoma in situ (n = 49), median HGRFS was comparable (gemcitabine: 12.2 months; Gem/Doce: 7.6 months [P = 0.12]). No significant differences were observed for secondary outcomes. In the 2-stage residual inclusion analysis, Gem/Doce was not associated with improved HGRFS (hazard ratio [HR], 1.09; 95% CI, 0.65-1.82; P = 0.80), including among patients with BCG-unresponsive disease (HR, 2.24; 95% CI, 0.96-5.24 [P = .06]). Low-grade adverse events were common (gemcitabine: 63%; Gem/Doce: 55% [P = 0.19]), but grade ≥3 adverse events were rare (2.3% vs. 2.4%). Limitations included imbalances in maintenance utilization (gemcitabine: 19%; Gem/Doce: 40%), baseline characteristics, gemcitabine dosing, and follow-up duration between cohorts.

CONCLUSIONS

In this multicenter study, Gem/Doce was not associated with improved outcomes compared with gemcitabine alone. Prospective trials are needed to quantify the specific contribution of docetaxel in NMIBC.