Sequential Endoluminal Doxorubicin and Gemcitabine Alternating Weekly with Sequential Mitomycin and Docetaxel for Recurrent Non-Muscle Invasive Urothelial Carcinoma.

Simple Summary: After failing multiple treatments for non-muscle invasive bladder cancer (NMIBC), patients with this disease face the prospect of radical bladder removal. However, many patients will wish to pursue additional bladder-sparing therapies or lack candidacy for such an invasive procedure. We aimed to report on a tertiary intravesical regimen of sequential doxorubicin and gemcitabine alternating weekly with docetaxel and mitomycin (Quad Chemo) for patients with high-risk NMIBC failing multiple previous treatments. We found in a population of 29 patients with 39 treated units (bladder and/or upper urinary tracts), 80% of the units were disease-free at 3 months and 43% were disease-free at 2 years following Quad Chemo treatment. However, disease progression was a concern with an estimated 43% of patients experiencing disease progression at 5 years. Lastly, side effects were not uncommon with 19 (66%) patients reporting any side effect and 7 (24%) ultimately stopping Quad Chemo due to side effects. Background: After first-line treatment failure, patients with non-muscle invasive urothelial carcinoma (NMIUC) are recommended to undergo radical cystectomy. However, those unable to pursue radical surgery or desiring bladder preservation require effective salvage therapies. Multi-agent treatment regimens are particularly useful for targeting the complex resistance mechanisms of recurrent UC. Herein, we report a regimen of sequential doxorubicin and gemcitabine alternating weekly with sequential docetaxel and mitomycin (Quad Chemo) for patients with recurrent high-risk NMIUC. Materials and Methods: We retrospectively identified all patients sequentially treated with 50 mg of doxorubicin followed by 1000 mg of gemcitabine alternating weekly with sequential 37.5 mg of docetaxel followed by 40 mg mitomycin-C between 2007–2024. Induction consisted of 8 weekly treatments, and, if disease-free, patients were initiated on monthly maintenance treatments for 2 years. Results: In total, 29 patients (39 treated units; 26 lower urinary tract, 13 upper urinary tract) with high-grade NMIUC were included in the final analysis. The cohort had high-risk features with a median of three prior induction therapies and with 38 (97%) units presented with either biopsy-proven CIS or presumed CIS in the context of high-grade urine cytology in the absence of tumorous lesions. There were 26 recurrences during follow-up, 17 in the lower tract and 9 in the upper tract. Among all of the treated units, the complete response rate was 80%, and 1- and 2-year recurrence-free survival was 60% and 43%, respectively. In total, 10 patients experienced disease progression yielding a 5-year progression-free survival of 57%. Five patients ultimately died due to bladder cancer yielding a 5-year cancer-specific survival of 83%. A total of 19 (66%) patients reported side effects during treatment, and 7 (24%) stopped treatment secondary to side effects. Conclusions: In a high-risk heavily pre-treated cohort, Quad Chemo rescued a significant portion of patients with recurrent NMIUC from disease relapse. However, progression events were considerable in the long term. Further prospective evaluation of this treatment regimen is warranted. [ABSTRACT FROM AUTHOR]