Data support combination intravesical chemotherapy for high-risk NMIBC

Sequential intravesical valrubicin and docetaxel (val/doce) demonstrated safety and efficacy as salvage therapy for patients with recurrent high-risk non–muscle invasive bladder cancer (NMIBC), according to data from a retrospective study published in European Urology Focus.¹

Ian M. McElree, MD

“We found that sequential intravesical valrubicin and docetaxel (or Val/Doce) was safe, well-tolerated, and provided meaningful bladder-preservation outcomes for a particularly high-risk population, the majority failing at least 2 prior therapies,” said lead author Ian M. McElree, MD, in correspondence with Urology Times®. “This study adds to the growing body of evidence supporting combination intravesical chemotherapy as a feasible option even after prior treatment failure. Nearly half of patients remained disease-free at 2 years, which is remarkable in this setting.”

For the study, the investigators retrospectively identified 139 patients with recurrent high-risk NMIBC who received treatment with val/doce between 2013 and 2024 at the University of Iowa. The median age of patients was 75 years (IQR, 69 to 81). Participants had a median of 2 prior lines of therapy; prior ttreatment included BCG in 66% of patients and gemcitabine/docetaxel in 96% of patients.

The primary end point was high-grade recurrence-free survival (HG-RFS).

At a median follow-up of 25 months (IQR, 10 to 51), 70 patients experienced a HG recurrence. Thus, the estimated HG-RFS rates were 58% at 1 year, 45% at 2 years, and 41% at 3 years. No factors were found to be associated with an increased risk of recurrence, including prior BCG (P = .81), pretreatment carcinoma in situ (P = .28), T1 disease (P = .46), nor urothelial carcinoma present in the prostatic urethra/ducts (PUC; P = .43).

Further, 22 patients experience disease progression. The estimated progression-free survival rates were 95% at 1 year, 84% at 3 years, and 70% at 5 years. PUC prior to val/doce induction, which was present in 27 patients, was found to be associated with an increased risk of progression (P = .02). No other factors were significantly associated with disease progression.

At 5 years, the estimated overall survival and cancer-specific survival rates were 68% and 91%, respectively.

In total, 73 patients (53%) experienced an adverse event (AE) during treatment. This translated to 94 AEs, which included 45 that were grade 1, 48 that were grade 2, and 1 that was grade 3. According to the authors, “The grade 3 AE was sepsis secondary to urinary tract infection requiring hospitalization and intravenous antibiotics.”

Overall, the most common AEs included bladder spasms (22%), urinary tract infection (9%), and hematuria (9%). AEs led to treatment discontinuation in 2 patients.

“As the treatment landscape becomes increasingly crowded with expensive agents, there’s real value in exploring intravesical approaches that are safe and readily available,” concluded McElree, who is an incoming resident at Vanderbilt University Medical Center in Nashville, Tennessee, and recent medical school graduate from the University of Iowa. “Moving forward, we’re focused on optimizing treatment sequencing—understanding when and how to use regimens like val/doce most effectively, and how to better match patients to salvage options based on tumor and patient-specific biomarkers.”

He added, “At the University of Iowa, we offer a range of bladder-sparing treatments through what we call the ‘Iowa Bladder-Sparing Algorithm’. This structured pathway includes options like val/doce and others, and we look forward to sharing outcomes from this broader cohort soon.”

REFERENCE

1. McElree IM, Steinberg RL, Hougen HY, et al. Extended Outcomes of Intravesical Valrubicin and Docetaxel as a Secondary Salvage Treatment for Recalcitrant High-risk Non-muscle-invasive Bladder Cancer. Eur Urol Focus. 2025:S2405-4569(25)00152-X. doi:10.1016/j.euf.2025.05.022