Introduction: Intravesical gemcitabine-docetaxel (Gem/Doce) has emerged as an efficacious and well-tolerated therapy for NMIBC. However, effective rescue therapies are needed for subsequent recurrences, particularly when cystectomy is refused or precluded. Current FDA-approved agents for BCG failures all show <20% 1 year response. We report our experience with sequential intravesical valrubicin and docetaxel (Val/Doce) as a rescue therapy for NMIBC.
Methods: We retrospectively identified all patients with recurrent NMIBC who were treated with Val/Doce between April 2013 and June 2021. Patients were treated with weekly sequential intravesical instillations of 800 mg valrubicin and 37.5 mg docetaxel for 6 weeks. Monthly maintenance of 2 years was initiated if disease free at first follow up. Analysis was stratified by low grade (LG) and high grade (HG) disease. The primary outcomes were recurrence-free survival (RFS) and HG RFS. Progression was defined as development of muscle invasive or metastatic disease or cystectomy. Survival was assessed using the Kaplan-Meier method, indexed from start of Val/Doce induction. Surveillance was performed according to AUA guidelines.
Results: Seventy-five patients with median follow-up of 21 (IQR: 13-37) months were included in the analysis. Previous intravesical failures included Gem/Doce (95%), BCG (72%), and both BCG and Gem/Doce (68%). Twelve patients with recurrent LG disease showed a 73% 2-year RFS with no HG recurrences (Table 1). Sixty-three patients had recurrent HG disease with a median of 2 prior induction courses. The 1 and 2-year HG RFS were 56% and 38%, respectively. Forty-two (56%) patients had CIS present. RFS was similar for those with and without CIS (p=0.63). Progression occurred in 12 (16%) patients. Ten patients (16%) underwent cystectomy and 2 (3%) died of metastatic bladder cancer. Overall, cancer-specific, and cystectomy-free survival were 88%, 96%, and 85% at 24 months, respectively. Common side effects were bladder spasms (24%), urinary frequency (13%), and dysuria (11%). Three patients could not tolerate a full induction course.
Conclusions: In a heavily pre-treated population, Val/Doce showed promising efficacy as a rescue treatment for patients with recurrent NMIBC. Further prospective evaluation of Val/Doce is needed.
Source of Funding: This work was supported by the John & Carol Walter Family Foundation and the Carver College of Medicine.
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