Sam S. Chang, MD, MBA

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 how to approach treatment for a younger (49-year-old) male veteran with bladder cancer, focusing on the rising rates among veterans, challenges with recurrent disease despite BCG therapy, various second- and third-line treatment options, including gemcitabine-docetaxel combination therapy and the importance of thorough monitoring for disease progression.

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 to manage the treatment of a 68-year-old woman with painless intermittent hematuria and positive cytology for high-grade urothelial cancer, addressing gender differences in diagnosis timing, the importance of repeat transurethral resection (TURBT) procedures, BCG therapy options, and considerations for radical cystectomy with pelvic organ preservation when BCG fails.

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 they approach a typical bladder cancer case of a 79-year-old man with hematuria, including initial diagnostic procedures, the importance of proper tumor measurement during resection, BCG therapy protocols, and management options for BCG-unresponsive disease with a focus on nadofaragene firadenovec (Adstiladrin).

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 non–muscle-invasive bladder cancer (NMIBC) is staged, graded, and treated according to risk stratification, with detailed explanations of low-, intermediate-, and high-risk categories and corresponding treatment pathways.

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.

The CR rate was 71% in patients with BCG-unresponsive NMIBC with CIS with or without papillary disease.

In this final episode, panelists conclude with reflections on the significant progress made in treating NMIBC over the past decade, particularly in the last 5 years. Looking ahead to 2024, experts in urology express excitement about investigational treatments (ie, cretostimogene grenadenorepvec and UGN 102), the potential for personalized medicine, emphasizing the need to understand molecular characteristics of the disease for better treatment customization. The session also highlights the importance of balancing quality of life with effective treatment strategies, and the prospect of utilizing emerging therapies early in the disease process.

This video segment explores various investigational strategies, including the use of agents like UGN 102, and recent clinical trials for intermediate-risk NMIBC. The conversation highlights the importance of balancing side effects with efficacy and the shift towards non-surgical management in treating intermediate-risk NMIBC and in the BCG-naive population.

This video episode discusses various new therapies and strategies for treating patients with high-risk BCG-unresponsive NMIBC. It includes a review of nadofaragene firadenovec-vncg, its FDA approval, dosing schedule, and patient response rates. The conversation also explores the practical aspects of treatment, such as the balance between efficacy and treatment frequency, and the potential sequencing of therapies in clinical practice.

This video segment provides insights into various innovative trials and agents being explored for high-risk BCG-unresponsive NMIBC. The discussion covers a range of approaches including oncolytic immunotherapy, gene therapy, systemic IO agents, antibody-drug conjugates, and cytokine therapies. It emphasizes the need for personalized dosing regimens based on individual immune responses and highlights the significance of longer-term efficacy evaluations beyond initial three-month response rates.

This episode provides an in-depth discussion on Cretostimogene Grenadenorepvec (CG), an investigational agent for high-risk BCG-unresponsive NMIBC, including the mechanism of action, its efficacy and safety data from clinical trial trials like CORE01 and BOND-003 (NCT04452591), and the rationale behind combining CG with anti-PD-1/PD-L1 antibodies. Experts also provide their insights on future directions in clinical development and application of CG in various NMIBC treatment scenarios, such as a monotherapy and in combination with IO, including its potential use in intermediate-risk disease.

This episode explores the potential of emerging therapies in providing effective treatment alternatives for challenging NMIBC cases. Current clinical trials and investigational treatments for high-risk, BCG-unresponsive NMIBC are highlighted, including the use of N-803, an IL-15 superagonist, in combination with BCG, and discusses TAR-200, an intravesical drug delivery system, which releases gemcitabine directly into the bladder over time.

Sam S. Chang MD, MBA leads a discussion of various treatment approaches for a hypothetical case of a 74-year-old female patient with T1 bladder cancer and associated CIS, exploring the necessity of repeat resections. The conversation emphasizes the importance of personalized treatment plans, considering BCG therapy, clinical trials involving immunotherapy, and the possibility of cystectomy, while also addressing the complexities and risks associated with high-grade bladder cancer in elderly patients.

This episode focuses on the complex management of recurrent low-grade bladder tumors and highlights the limitations and challenges of current treatments, including intravesical chemotherapy and BCG, and underscores the need for better therapies and clinical trials in this area.

The various treatment approaches for NMIBC in the context of a BCG shortage, with a focus on initial cases, are shared. Urologists discuss their strategies for treating a hypothetical patient with a 3 cm bladder tumor, weighing options like perioperative chemotherapy, the importance of thorough resection, and adapting treatment protocols based on tumor characteristics and the ongoing BCG shortage.

The impact of the BCG shortage on the treatment of bladder cancer, exploring various strategies adopted by urologists to optimize patient care. The conversation highlights the importance of risk stratification in deciding treatment protocols, considering factors like tumor size, location, multifocality, and histology, as well as patient age and overall health.

Experts discuss grading, staging, and risk stratification of Non-Muscle Invasive Bladder Cancer (NMIBC). Panelists highlight differentiation between the risks of recurrence and progression, emphasizing the importance of categorizing patients into low, intermediate, and high-risk groups based on various factors, including tumor size, grade, and history of recurrence. The importance of continuous prospective observation of patients with NMIBC is emphasized.

Experts in urology discuss the importance of evaluation to accurately identify the stage and grade of NMIBC, which plays a crucial role in determining the risk category focusing on the distinction between low and high-grade tumors and the significance for each patient with NMIBC​​.