Introduction:

Bacillus Calmette-Guerin (BCG) is currently recommended as adjuvant treatment following complete transurethral resection of bladder tumor for high-risk non-muscle invasive bladder cancer (NMIBC) and has been shown to be superior to single-agent chemotherapy regimens. Initially utilized due to ongoing BCG shortages, intravesical gemcitabine and docetaxel (Gem/Doce) has been increasingly utilized at our institution as first-line therapy. We aimed to compare, over an overlapping time period, the oncologic outcomes of patients with high-risk treatment-naïve NMIBC treated with Gem/Doce versus BCG as a first-line adjuvant therapy.

Methods:

We retrospectively identified 312 patients with high-risk treatment naïve NMIBC treated at our institution between January 2011 through December 2021; 174 treated with BCG and 138 treated with Gem/Doce. After complete TURBT, patients received a 6 weekly induction regimen of either sequential intravesical gemcitabine (1 gram) and docetaxel (37.5 mg) or 1 vial of BCG (with or without 50 million units of IFNα-2b). Maintenance regimens were initiated if disease free at first follow-up. Outcomes included recurrence-free survival (RFS), high-grade recurrence-free survival (HG-RFS), cystectomy-free survival (CFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Survival probabilities were estimated and plotted using the Kaplan-Meier method. Cox regression models were used to evaluate the effect of patient, disease, and treatment characteristics on outcomes. Adverse events were reported using CTCAE v5.

Results:

Median follow-up for patients receiving BCG and Gem/Doce was 49 and 23 months, respectively. Pre-treatment stage was similar between patients receiving BCG and Gem/Doce (p=0.46). Other baseline characteristics including gender, smoking status, tumor size, and multifocality were similar between groups (all p>0.05). RFS estimates at 6, 12, and 24 months were 72%, 67%, and 62% in the BCG group and 90%, 83%, and 78% in the Gem/Doce group, respectively (Figure 1). On multivariable Cox regression analyses controlling for age, gender, treatment year, and presence of CIS, Gem/Doce treatment was associated with superior RFS (HR 0.56, p=0.02) and HG-RFS (HR 0.57, p=0.04) compared to BCG (Table 1). PFS was 97% at 2-years for Gem/Doce versus 92% for BCG (p=0.02); however, CFS and CSS were not statistically different (both p=0.06). Induction with BCG was associated with greater treatment discontinuation rates than induction with Gem/Doce (9.2% versus 2.9%, p=0.02). 

Conclusion:

Gem/Doce is a reasonable alternative treatment for high-risk NMIBC in the setting of the BCG shortage. These data provide benchmark outcomes to support ongoing prospective single-arm and randomized studies of these agents, to further clarify the role of Gem/Doce as a first-line treatment.

Funding: This work was supported in part by the John & Carol Walter Family Foundation, the Cancer Center Support Grant, and by the Carver College of Medicine.