Introduction:

Effective treatment of very-high-risk (VHR) non-muscle invasive bladder cancer (NMIBC), as defined by the European Association of Urology (EAU), remains challenging due to its high risk of progression. Given suboptimal efficacy of Bacillus Calmette-Guérin (BCG), the EAU guidelines recommend early radical cystectomy (RC) for patients with VHR NMIBC. However, effective bladder-sparing alternatives are needed to mitigate the morbidity and risk of overtreatment associated with RC. Our study aims to compare the oncological outcomes of patients with VHR NMIBC treated with sequential intravesical gemcitabine and docetaxel (Gem/Doce) or BCG.

Methods:

A retrospective analysis was conducted to compare the oncological outcomes of 129 treatment-naïve patients with VHR NMIBC. VHR NMIBC was defined according to criteria summarized in Figure 1. Among these patients, 65 received intravesical Gem/Doce and 64 received BCG therapy. The comparison was performed using Cox regression. Patients received either sequential intravesical Gem 1 g and Doce, 37.5 mg, or 1 vial of BCG. Induction treatments were administered once per week for 6 weeks. Maintenance regimens were initiated if the patient was disease-free at the first follow-up visit.

Results:

Median follow-up for survival was 48 months (IQR, 26-74 months) in the BCG group and 23 months (IQR, 15-36 months) in the Gem/Doce group. Recurrence-free survival (RFS) at 12 and 24 months was 63% and 54% for the BCG group compared to 79% and 73% for the Gem/Doce group, respectively (Figure 2a). Progression-free survival (PFS) at 24 months was 88% for the BCG group and 97% for the Gem/Doce group (Figure 2b). Cystectomy free-survival at 24 months was 90% in the BCG group and 97% in the Gem/Doce group. Gem/Doce demonstrated a reduced risk of tumor recurrence compared to BCG (hazard ratio: 0.55; 95% confidence interval: 0.30-0.99; p = 0.05). Additionally, patients in the Gem/Doce group were less likely to discontinue therapy (3.1% vs. 14.1%; p = 0.03).

Conclusion:

In this study, select patients with “favorable” VHR NMIBC (without histologic variants, lymphovascular invasion (LVI), and carcinoma in situ (CIS) of the prostatic urethra)—can be efficiently treated with BCG or Gem/Doce. Furthermore, compared to patients treated with BCG, those who received Gem/Doce showed improved tolerance and a higher RFS. Large-scale, prospective trials are needed to confirm our results.

Funding: N/A