Bladder-Sparing Breakthroughs: Novel FDA-Approved Treatment Options for NMIBC

EP: 1.Current Standards of Care and Shifting Strategies in NMIBC

EP: 2.NMIBC Treatment Decisions in the Age of BCG Shortages

EP: 3.Expert Discussion on BCG-Unresponsive NMIBC

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EP: 4.Bladder-Sparing Breakthroughs: Novel FDA-Approved Treatment Options for NMIBC

EP: 5.Weighing the Risks and Benefits of Bladder-Sparing Agents vs Cystectomy

EP: 6.What’s Next for NMIBC: The Immunotherapy and Gene Therapy Pipeline

EP: 7.Topline Data From the BOND-003 Trial in NMIBC

EP: 8.Immunotherapy in NMIBC: Key Results Safety Profile From BOND-003 Trial

The treatment landscape for high-risk, BCG-unresponsive non–muscle-invasive bladder cancer has expanded significantly, with 3 FDA-approved bladder-sparing therapies now available: pembrolizumab, nadofaragene firadenovec (Adstiladrin), and nogapendekin alfa-inbakicept (Anktiva). Pembrolizumab, a PD-1 inhibitor, was the first approved agent in this space. While systemically used in various cancers, its modest 19% 1-year response rate limits its use to patients who cannot undergo cystectomy or tolerate intravesical therapies. Despite its limited efficacy, it remains an option due to ease of administration—an intravenous infusion every 3 weeks.

Nadofaragene is the first FDA-approved intravesical gene therapy and has gained popularity due to its tolerability and convenient quarterly dosing. With a 1-year response rate of approximately 24%, and long-term bladder preservation in some patients extending to 5 years, it is frequently used as a first- or second-line salvage therapy. Nogapendekin, the newest agent, is an IL-15 superagonist used in combination with BCG. It offers the highest reported 1-year complete response rate at approximately 45%. However, its use is complicated by ongoing BCG shortages, although a recently approved recombinant BCG may help alleviate this issue.

In addition to FDA-approved treatments, many clinicians continue to use gemcitabine-docetaxel (gem-doce) off-label due to its strong retrospective efficacy, low cost, and tolerable adverse effect profile. While not yet supported by prospective trial data, it is often preferred as first-line therapy due to accessibility and affordability. Still, logistical and financial barriers—such as the need for chemotherapy-certified staff and formulation infrastructure—limit its widespread adoption. Despite differences in trial design across therapies, having multiple treatment options enables more personalized approaches, and prospective validation studies on regimens like gem-doce are eagerly anticipated.