Extended Outcomes of Intravesical Valrubicin and Docetaxel as Secondary Salvage Treatment for Recalcitrant High-risk Non-muscle-invasive Bladder Cancer - Expert Commentary
This retrospective cohort study analyzed 139 patients with recurrent HR-NMIBC treated with Val/Doce at the University of Iowa between 2013 and 2024. Patients received weekly sequential intravesical instillations of 800 mg valrubicin followed by 37.5 mg docetaxel for six weeks, with monthly maintenance therapy for up to two years if disease-free at first surveillance. The primary outcome was high-grade recurrence-free survival (HG-RFS), with adverse events reported using the Common Terminology Criteria for Adverse Events version 5.
The final cohort had a median age of 75 years (interquartile range 69-81), with 23 (17%) female patients. Median follow-up was 25 months (10-51). Patients were heavily pretreated with a median of two prior treatments: 133 (96%) had prior gemcitabine/docetaxel treatment and 92 (66%) had prior BCG, with 40 (44%) meeting BCG-unresponsive criteria. At first surveillance, 88 (63%) patients demonstrated complete response. The HG-RFS rates were 58% (95% CI 49-66%), 45% (35-54%), and 41% (31-51%) at 1, 2, and 3 years, respectively (p values for confidence intervals not provided). Progression-free survival rates were 95% (89-97%), 84% (74-90%), and 70% (51-83%) at 1, 3, and 5 years, respectively. Cancer-specific survival was 91% (80-96%) at 5 years. During follow-up, 18 patients underwent radical cystectomy, resulting in cystectomy-free survival of 77% (63-86%) at 5 years.
Adverse events occurred in 73 patients (53%), with 94 total events: 45 grade 1, 48 grade 2, and one grade 3. The most common adverse events were bladder spasms in 30 patients (22%), urinary tract infections in 13 patients (9%), and hematuria in 12 patients (9%). The single grade 3 event was sepsis secondary to urinary tract infection requiring hospitalization. Only two patients discontinued treatment due to adverse events. Univariate analysis revealed no factors significantly associated with increased recurrence risk (p = 0.81 for prior BCG, p = 0.28 for pretreatment CIS, p = 0.46 for T1 disease, p = 0.43 for prostatic urethral carcinoma). However, prostatic urethral carcinoma prior to Val/Doce induction was associated with increased progression risk (p = 0.02).
This study demonstrates that Val/Doce provides safe and efficacious salvage therapy for recurrent HR-NMIBC, with nearly two-thirds achieving complete response and 41% remaining recurrence-free at three years. The treatment showed excellent tolerability with minimal severe toxicity. However, patients with prostatic urethral involvement had significantly higher progression rates, warranting careful counseling regarding bladder-sparing versus radical surgical options. Study limitations include its retrospective design, potential selection bias, and single-institution experience.
Written by: Bishoy M. Faltas, MD, Chief Research Officer, Englander Institute for Precision Medicine, Gellert Family - John P. Leonard, MD, Research Scholar, Associate Professor of Medicine, Cell and Developmental Biology, Weill Cornell Medicine, New York- Presbyterian Hospital, NY
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