Mark D. Tyson, II, MD, MPH

Panelists discuss current FDA-approved treatments for BCG-unresponsive carcinoma in situ, noting varying response rates among pembrolizumab, nadofaragene, and BCG combined with IL-15 superagonist, while highlighting promising investigational combination immunotherapies like oncolytic viruses and checkpoint inhibitors that may improve outcomes in this challenging patient population.

Panelists discuss emerging data comparing bladder-sparing therapies to radical cystectomy in BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), highlighting the nuanced trade-offs in oncologic outcomes and quality of life, and emphasizing the need for shared decision-making as prospective studies like CISTO refine patient selection for personalized treatment strategies.

Panelists discuss how recent advancements in NMIBC treatment, including the approval of nadofaragene firadenovec, pembrolizumab, and intravesical therapies like TAR-200, have reshaped care for BCG-unresponsive patients, with promising developments and ongoing trials at AUA 2025 paving the way for more personalized and effective treatment strategies in the future.

Panelists discuss how leveraging resources such as patient assistance programs, insurance navigators, clinical trial databases, advocacy groups, and oncology support services can help overcome access barriers, ensuring that NMIBC patients receive timely access to novel treatments like nadofaragene firadenovec and pembrolizumab.

Panelists discuss how overcoming challenges such as cost, insurance coverage, regulatory hurdles, patient selection, and the need for education is crucial for improving access to novel therapies like nadofaragene firadenovec and pembrolizumab, ultimately enhancing outcomes for NMIBC patients.

Panelists discuss the expanding treatment options for BCG-unresponsive high-risk non–muscle-invasive bladder cancer, highlighting the benefits and limitations of FDA-approved therapies like pembrolizumab, nadofaragene, and nogapendekin, alongside off-label use of gemcitabine-docetaxel, as clinicians strive to balance efficacy, accessibility, and individualized care amid ongoing resource challenges.

Panelists discuss the evolving definition of BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), emphasizing its critical role in identifying patients who fail adequate BCG therapy, guiding next-line treatment decisions, and determining eligibility for clinical trials exploring novel therapeutic options.

Panelists discuss how recent trials, including KEYNOTE-057, QUILT-3.032, and CORE-001, highlight the promising efficacy, durability, and manageable safety profiles of novel treatments like pembrolizumab, nogapendekin alfa inbakicept, and nadofaragene firadenovec, while also exploring the potential of combination therapies and novel intravesical options like TAR-200 and UGN-102 for improving outcomes in non–muscle-invasive bladder cancer (NMIBC).

Panelists discuss how the ongoing ABLE-32 and ABLE-41 trials are exploring the efficacy and safety of nadofaragene firadenovec in different NMIBC patient populations, with ABLE-32 focusing on intermediate-risk patients and ABLE-41 examining real-world effectiveness and safety.

Panelists discuss how the ongoing BCG shortage has forced clinicians to adapt treatment strategies for non–muscle-invasive bladder cancer (NMIBC), balancing resource constraints with patient outcomes through dose adjustments, chemotherapy substitution, and earlier cystectomy, while emphasizing the importance of maintaining trial eligibility and adhering as closely as possible to evidence-based protocols.

Panelists discuss evolving strategies for managing non–muscle-invasive bladder cancer (NMIBC), highlighting how risk stratification, resource limitations, and emerging therapies like gemcitabine-docetaxel are shaping treatment decisions, while emphasizing the urgent need for predictive tools and biomarkers to guide personalized care.

Panelists discuss how real-world data from a recent Mayo Clinic study confirms the promising efficacy and favorable safety profile of nadofaragene firadenovec in BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), highlighting high cystectomy-free and overall survival rates, with longer follow-up needed to assess response durability.

Panelists discuss how nogapendekin alfa, an intravesical immunotherapy that stimulates a localized immune response, combined with BCG therapy, provides a novel dual approach for treating BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), targeting both local and systemic immune responses.

Panelists discuss how pembrolizumab, a PD-1 inhibitor, offers a systemic immunotherapy option for high-risk, BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) by enhancing the immune system’s ability to target cancer cells, with intravenous administration and careful monitoring for immune-related adverse effects.

Panelists discuss how recently FDA-approved therapies, including nadofaragene firadenovec, gemcitabine, and docetaxel, offer alternative treatment options for BCG-unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC), each with distinct mechanisms and administration methods.

Panelists discuss how maintenance BCG therapy and vigilant surveillance are essential for sustaining disease control in NMIBC patients, with treatment schedules and monitoring tailored to individual risk and tolerance.

Panelists discuss how timely identification of BCG-unresponsive NMIBC through defined response criteria enables dynamic risk stratification and guides critical decisions about escalating care to alternative treatments.

Panelists discuss how specific tumor characteristics, such as papillary architecture and presence of carcinoma in situ, guide risk-adapted treatment decisions in non–muscle-invasive bladder cancer.

Panelists discuss how precise risk stratification in non–muscle-invasive bladder cancer enables physicians to tailor treatment and surveillance strategies based on individual patient risk profiles.

A panelist discusses how urologists considering newer treatment modalities for BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) should be encouraged by positive clinical trial data while ensuring proper training, patient selection, and establishment of treatment protocols in their practice.

A panelist discusses how the ability to administer newer non–muscle-invasive bladder cancer (NMIBC) treatments in local urology practices rather than specialized oncology centers reduces patient burden and travel requirements while suggesting that increased education and support could help more health care providers adopt these treatment options.

A panelist discusses how less frequent treatment administration schedules and simpler delivery requirements of newer gene therapies reduce clinic resource burden by minimizing staff time, equipment usage, and biosafety requirements, allowing for more efficient allocation of health care resources.

A panelist discusses how treatment decisions for BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) involve careful consideration of patient preferences, long-term cost-effectiveness, and available financial assistance programs, balancing the higher upfront costs of newer therapies with their potential economic benefits from reduced recurrence rates and treatment frequency.

A panelist discusses how targeted gene therapy has revolutionized BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) treatment through agents like nadofaragene firadenovec, which shows promising complete response rates at 3 months, though long-term follow-up remains crucial for assessing durability of response and comparing real-world outcomes with clinical trial data.

A panelist discusses how BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) has evolved from having limited treatment options beyond radical cystectomy to now having several therapeutic alternatives including intravesical chemotherapy and immunotherapy, though each current option comes with its own efficacy limitations and adverse effect profiles that must be carefully weighed against patient factors.

"In terms of results, complete response rate at any time point for the cohort was 74.5%," says Mark D. Tyson, II, MD, MPH.