Extended Outcomes of Intravesical Valrubicin and Docetaxel as a Secondary Salvage Treatment for Recalcitrant High-risk Non-muscle-invasive Bladder Cancer.

BACKGROUND AND OBJECTIVE: After multiple treatment failures, clinical practice guidelines recommend that patients with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) undergo radical cystectomy (RC). However, since many patients will be either unfit or averse to radical surgery, additional bladder-sparing therapies are needed. Herein, we report the efficacy of sequential intravesical valrubicin and docetaxel (Val/Doce) as a salvage therapy for patients with recurrent HR-NMIBC.

METHODS: We retrospectively identified all patients with recurrent HR-NMIBC treated with Val/Doce between 2013 and 2024 at the University of Iowa. The primary outcome was high-grade recurrence-free survival (HG-RFS). Adverse events were reported using Common Terminology Criteria for Adverse Events version 5. Patients received weekly sequential intravesical instillations of 800 mg valrubicin and 37.5 mg docetaxel for 6 wk. Monthly maintenance of 2 yr was initiated if the patients were disease free at the first follow-up.

KEY FINDINGS AND LIMITATIONS: The final cohort included 139 patients with a median (interquartile range) follow-up of 25 (10-51) mo. Patients had a median of two prior treatments: 92 (66%) had prior bacillus Calmette-Guérin and 133 (96%) had prior a Gem/Doce treatment. Tumor pathology immediately prior to Val/Doce induction included 53 carcinoma in situ (CIS), 19 T1HG, six T1HG + CIS, 37 TaHG, 21 TaHG + CIS, and three TaLG + CIS cases. Additionally, 27 patients had urothelial carcinoma present in the prostatic urethra/ducts (PUC), and 38 had any history of PUC. The HG-RFS rates at 1, 2, and 3 yr were 58%, 45%, and 41%, respectively. The progression-free survival rates at 1, 3, and 5 yr were 95%, 84%, and 70%, respectively. The cancer-specific survival rate was 91% at 5 yr. Upon a univariate analysis, there were no factors associated with an increased risk of recurrence. However, PUC prior to Val/Doce induction was associated with an increased risk of progression (p = 0.02). Adverse events occurred in 73 patients (53%), including one grade 3 event.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Val/Doce was safe and efficacious in patients with recurrent HR-NMIBC. The capacity to delay progression and avoid RC in a significant proportion of patients highlights its potential as a valuable treatment option in this challenging clinical context and warrants prospective evaluation.