Mark D. Tyson, MD, MPH

"The implication for real-world decision-making is that this drug appears to hold up to what was seen in the trial," says Mark D. Tyson II, MD, MPH.

Panelists discuss how it would be preferred that BCG monotherapy not remain the first-line treatment for intermediate-risk and high-risk disease within the next 10 years. It is encouraged that the future of first-line treatment be a noninfectious agent that would be easier to develop and include more data.

Panelists discuss how PD-L1 inhibitors such as durvalumab and sasanlimab represent a promising frontier in non–muscle-invasive bladder cancer (NMIBC) treatment. These immunotherapies work by unleashing the body’s immune response against cancer cells, potentially offering new options for patients whose disease doesn’t respond to conventional therapies such as BCG. Their ongoing phase 3 trials could establish immunotherapy as a valuable addition to the NMIBC treatment landscape.

Panelists discuss how both TAR-200 and UGN-102/103 represent innovative approaches to intravesical drug delivery for bladder conditions. TAR-200 uses a novel silicone-based system designed for controlled gemcitabine release, potentially offering extended drug exposure compared with conventional instillations. UGN-102 and UGN-103 employ a proprietary RTGel technology that transforms from liquid to gel form at body temperature, allowing for longer retention of mitomycin (UGN-102) and high-dose botulinum toxin (UGN-103), respectively, in the bladder.

Panelists discuss how cretostimogene grenadenorepvec is an intravesical oncolytic virus therapy targeting BCG-unresponsive bladder cancer through selective replication in tumor cells and immune stimulation via granulocyte-macrophage colony-stimulating factor expression.

Panelists discuss how for patients with BCG-unresponsive bladder cancer, treatment selection depends on key factors including tumor characteristics (carcinoma in situ vs papillary), patient fitness, and preferences. Standard options include radical cystectomy (the gold standard) or bladder-preserving approaches such as pembrolizumab, intravesical chemotherapy, or clinical trials. The decision requires careful individualization based on risk stratification, comorbidities, and shared decision-making.

Panelists discuss how FDA approvals have expanded options for BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), with pembrolizumab, nogapendekin alfa inbakicept-pmln, and nadofaragene firadenovec-vncg offering new immunotherapy and gene therapy approaches.

Panelists discuss how BCG-unresponsive bladder cancer is defined by disease persistence/recurrence within 6 to 12 months of adequate BCG therapy. Treatment options include cystectomy, intravesical chemotherapy, immunotherapy, or clinical trials.

Panelists discuss how low-risk non–muscle-invasive bladder cancer (NMIBC) requires transurethral resection of bladder tumor (TURBT) with surveillance. Intermediate-risk disease needs adjuvant intravesical chemotherapy. High-risk cases receive BCG induction/maintenance therapy after TURBT, with close monitoring.

Panelists discuss their views on using cretostimogene as monotherapy versus combination therapy, the importance for urologists to stay updated on advances for managing BCG-unresponsive NMIBC, and the potential impact of combining cretostimogene with pembrolizumab on addressing unmet needs in NMIBC care.

Panelists discuss whether the trial results support investigating cretostimogene with other checkpoint inhibitors and provide insights into notable ongoing trials exploring cretostimogene for intermediate- or high-risk NMIBC, such as BOND-003 and PIVOT-006.

Panelists discuss how the combination therapy of cretostimogene plus pembrolizumab offers a promising new approach for managing BCG-unresponsive non-muscle-invasive bladder cancer, highlighting its potential benefits and the implications of its FDA Breakthrough Therapy Designation for clinical practice.

Key opinion leaders examine the comparative safety profiles and response durations of combination therapy versus monotherapy in the treatment of BCG-unresponsive carcinoma in situ with or without papillary disease.

Experts discuss the results of the CORE-001 Trial.

Experts compare Cretostimogene and BCG Administration Methods

Experts discuss the patient quantity and qualifications for the CORE-001 trial.

Experts give an overview of the ASCO 2024 data.

Experts discuss available therapies beyond BCG.

Experts discuss the rate of recurrence following first-line BCG therapy.

Trinity Bivalacqua, MD, PhD and Mark Tyson, MD, MPH discuss the current shortage of BCG therapy and how that has impacted clinical practice management.

After briefly introducing themselves, Trinity Bivalacqua, MD, PhD and Mark Tyson, MD, MPH discuss approximately how many newly diagnosed bladder cancer patients have non-muscle invasive bladder cancer, or NMIBC.

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.