Introduction:

Bacillus Calmette-Guerin (BCG) is currently recommended as first-line treatment following complete transurethral resection of bladder tumor (TURBT) for high-risk non-muscle invasive bladder cancer (NMIBC) and high-risk substrata of intermediate-risk disease. Particularly during BCG shortage, intravesical gemcitabine and docetaxel (Gem/Doce) is a promising alternative therapy in this setting, with prospective evaluation underway. However, due to the recent utilization of Gem/Doce, optimal pathways to treat recurrent disease are undefined. In particular, the efficacy of subsequent BCG for recurrent NMIBC after first-line Gem/Doce is unknown. Herein, we aimed to characterize the efficacy of BCG in the treatment of recurrence after Gem/Doce for NMIBC.

Methods:

We retrospectively identified 19 patients with NMIBC treated at our institution between January 2018 through April 2024 with BCG after Gem/Doce failure. After complete TURBT, patients received a 6 weekly induction regimen of 1 vial of BCG (with or without 50 million units of IFNα-2b and/or interleukin 2). Maintenance therapy was initiated if disease free at first follow-up. Outcomes assessed included recurrence-free survival (RFS), high-grade recurrence-free survival (HG-RFS). Survival probabilities were estimated and plotted using the Kaplan-Meier method. RFS and HG-RFS were defined as time from the start of BCG induction to recurrence or HG recurrence, respectively. Recurrence was defined as tumor relapse in the bladder or prostatic urethra in males.

Results:

Median follow-up was 27 months. Of the 19 patients included in the study, median age was 67 and 21% of patients were female. All patients were treatment-naïve prior to Gem/Doce induction (19 HG, 3 LG). The median time to Gem/Doce failure was 8 months. Pathology prior to BCG treatment included TaHG in 6, CIS in 6, TaLG in 4 (1 with focal component of HG disease), and T1HG in 3. RFS estimates at 12 and 24 months were 44% and 36%, respectively (Figure 1). HG-RFS in the cohort of patients with HG disease prior to Gem/Doce was 53% at 1 year (Figure 2). Two patients ultimately elected for cystectomy with pathology of pT2N0 and pT1N0. One patient developed metastatic urothelial carcinoma despite a lack of muscle invasive disease. One patient was unable to finish a full BCG induction due to side effects.

Conclusion:

In a cohort of patients with recurrent NMIBC, intravesical BCG was a reasonable treatment option following Gem/Doce failure. Larger studies are needed. 

Funding: The John & Carol Walter Family Foundation