NMIBC

High-Risk/BCG Naïve: Treatment of Choice

by Michael A. O'Donnell, MD, FACS | Feb 2025

Michael A. O’Donnell, MD, discusses BCG’s role as the standard treatment for non-muscle invasive bladder cancer (NMIBC).

Therapy for High Risk NMIBC

by Colin P. N. Dinney, MD | Aug 2024

Colin P.N. Dinney, MD, defines the criteria that categorize patients as high-risk, such as tumor grade, size, and recurrence history. He underscores the importance of early and accurate diagnosis using advanced imaging techniques and molecular markers, which play a crucial role in guiding treatment decisions.

He focuses on Bacillus Calmette-Guérin (BCG) therapy, the gold standard for high-risk NMIBC. Dr. Dinney reviews BCG’s mechanisms of action, administration protocols, and factors influencing its efficacy. He also addresses the challenges posed by BCG shortages and the emergence of BCG-unresponsive disease, highlighting the need for alternative therapeutic strategies.

Further, Dr. Dinney discusses the potential of immune checkpoint inhibitors, targeted therapies, and gene therapy in the context of high-risk NMIBC. He presents data from recent clinical trials that demonstrate the promising results of these innovative approaches in achieving durable responses and reducing recurrence rates.

Bladder Cancer: Optimizing Detection and Minimally-Invasive Management

by Alejandro R. Rodriguez, MD | May 2024

Alejandro R. Rodriguez, MD, discusses detection and minimally invasive management of bladder cancer. Dr. Rodriguez begins by noting that bladder cancer is the 10th most-commonly diagnosed cancer worldwide, and presents the American Urological Association (AUA) risk stratification that provides the basis for non-muscle-invasive bladder cancer (NMIBC) management.

Dr. Rodriguez notes that the most frequent treatment for NMIBC is Transurethral Resection of Bladder Tumor (TURBT.) While he contends that conventional TURBT is the best tool for clinical staging of NMIBC, he enumerates the risks and drawbacks of the procedure.

Dr. Rodriguez then describes narrow-band imaging (NBI) as an additional modality, and presents data showing that TURBT performed in NBI modality reduces NMIBC recurrence risk. Further, NBI with white light cystoscopy TURBT may lower recurrence risk with little-to-no effect on risks of adverse events.

Finally, Dr. Rodriguez turns to the role of TUR in muscle-invasive bladder cancer (MIBC), with a focus on clinical staging, histology and grade, and bladder preservation options. He notes that trimodality therapy is the primary option for patients with MIBC that seek bladder preservation as an alternative to radical cystectomy.

NMIBC Post-FDA Approval of New Drugs

by Guilherme Godoy, MD, MS | Jan 2024

Guilherme Godoy, MD, MS, explores recently FDA-approved treatments for NMIBC high-risk patients, with a focus on alternatives for BCG-unresponsive patients. He examines studies comparing the effectiveness of drug-based and gene-based therapies for the treatment of NMIBC against BCG, including:

Pembrolizumab
GemDOCE
Adstiladrin (Nadofaragene Firadenovec-vngc)

Clinical Trials for BCG-Naive and BCG-Unresponsive NMIBC

by Amirali Salmasi, MD | Jul 2023

Amirali Salmasi, MD, delves into a comprehensive discussion on risk stratification and treatment options for BCG-naive and BCG-unresponsive bladder cancer. In his enlightening presentation, Dr. Salmasi provides a thorough examination of the diverse risk groups, elucidating the distinctions between low risk, intermediate risk, and high risk based on tumor grade and size. Moreover, he delves into the crucial aspects of adequate BCG treatment and outlines the criteria for BCG unresponsiveness, enhancing our understanding of these critical factors.

Furthermore, Dr. Salmasi takes us on an exploratory journey through the realm of treatment approaches for bladder cancer. He shares insights on the exciting possibilities offered by sequential chemo, hyperthermia, immunotherapy, and targeted therapy, elaborating on their respective mechanisms and potential benefits. To bolster his insights, Dr. Salmasi highlights key studies and trials conducted, underscoring the promising outcomes that have been observed.

Bladder Cancer Risk Stratification: Moving from the Old to the New

by Joshua J. Meeks, MD, PhD | Mar 2023

Joshua J. Meeks, MD, PhD, discusses risk stratification and treatment options for patients with non-muscle-invasive bladder cancer (NMIBC).

Controversies in NMIBC: Guidelines and Beyond

by Sam S. Chang, MD, MBA | Mar 2023

Sam S. Chang, MD, MBA, discusses NMIBC guidelines, best practices, and controversies related to risk-stratification, surveillance, and treatment strategies.

Enhanced Techniques of NMIBC Detection

by Mark Tyson II, MD, MPH | Dec 2022

Dr. Mark D. Tyson, II, MD, MPH, moderates this session by discussing the critical need for precise detection techniques in managing NMIBC.

wRVUs: Do They Really Measure the Workload and Complexity of What We Do?

by Raj S. Pruthi, MD, MHA, FACS | Aug 2022

Raj S. Pruthi, MD, MHA, FACS, Professor in the Department of Urology at the University of California San Francisco, discusses how work Relative Value Units (wRVUs) correlate with the work urologists perform.

Non-Muscle Invasive Bladder Cancer: Guidelines-Based Approach

by Raj S. Pruthi, MD, MHA, FACS | May 2022

Raj S. Pruthi, MD, MHA, FACS, Professor in the Department of Urology at the University of California, San Francisco, reviews the American Urological Association (AUA)-Society of Urologic Oncology (SUO) guidelines on diagnosing and treating non-muscle invasive bladder cancer (NMIBC). He begins with some statistics, relating that in 2017, there were approximately 79,000 new cases of bladder cancer, 16,800 deaths, and greater than 500,000 survivors. Dr. Pruthi observes that bladder cancer is a disease of older individuals, and he predicts that the population of bladder cancer patients will increase as the population ages. He then highlights key facts about NMIBC, explaining that most patients recur, some progress, and the ability to predict recurrence and progression is based on patient-specific disease characteristics. Dr. Pruthi introduces the 2016 AUA/SUO guidelines, noting that the panel featured a patient advocate. He goes over the guidelines point by point, starting with diagnosis. Dr. Pruthi underscores the importance of performing a complete visual transurethral resection of bladder tumor (TURBT) at initial diagnosis, explaining that incomplete TURBT is a contributing factor to early recurrences. He notes that risk calculators for NMIBC are limited by lack of applicability to current populations, and also that no study has evaluated the effectiveness of urinary biomarkers to decrease mortality or improve outcomes compared with standard diagnostic methods. When discussing guidelines around treatment, Dr. Pruthi emphasizes the importance of re-resecting T1 disease since understaging occurs in about 30% of cases and patients with residual T1 (after presumed complete resection) have up to an 80% chance of progression. He also discusses guidelines around BCG administration and BCG relapse. Dr. Pruthi then looks at cystectomy, arguing that waiting until progression to muscle invasion may prove fatal. He concludes by discussing guidelines around follow up.

Updating the Definitions, Endpoints, and Clinical Trial Designs for Bladder Cancer

by Amirali Salmasi, MD | Apr 2022

Amirali Salmasi, MD, Assistant Professor of Urology at the University of California, San Diego, reviews risk stratification guidelines for non-muscle invasive bladder cancer (NMIBC) from the American Urological Association (AUA) and European Association of Urology (EAU); pointing out that the AUA classifies solitary high-grade (HG) Ta lesions ≤3cm classified as intermediate risk (IR-Ta) while the EAU recommends all HG tumors be classified as high-risk. Dr. Salmasi then presents data suggesting that, indeed, all HG Ta lesions should be considered high risk, supporting the EAU risk stratification model. He then reviews recommendations from the International Bladder Cancer Group, including definitions, end points, and clinical trial designs for NMIBC for both BCG-naive and BCG-unresponsive patients. For BCG-naive patients, Dr. Salmasi defines the clinically significant outcome of an absolute difference of 10 percent in the percentage of patients with recurrence at two years. For BCG-unresponsive patients with carcinoma in situ (CIS), a clinically meaningful magnitude of effect is an initial complete response rate of 50 percent at six months and a durable response rate of 30 percent at 12 months and 25 percent at 18 months; for those with papillary disease, it is a recurrence-free rate of 30 percent at 12 months and 25 percent at 18 months. Dr. Salmasi then shares information refining neoadjuvant therapy clinical trial design for muscle-invasive bladder cancer (MIBC) before cystectomy, citing level-one evidence that says neoadjuvant chemotherapy (NAC) should be offered to any “fit” patient before radical cystectomy (RC). He discusses eligibility and staging before discussing treatment options, posing questions about appropriate control arms for neoadjuvant trials as well as what number of neoadjuvant therapy cycles might be ideal, acknowledging that the best combination of treatment options remains uncertain. Dr. Salmasi discusses primary endpoints for neoadjuvant trials before shifting to a discussion on the future of trial design. He outlines some potential improvements to trial design, including sample size re-estimation; adaptive enrichment; seamless design; multi-arm, multistage (MAMS) trials; and biomarker-based adaptive study. Dr. Salmasi then outlines the benefits and limitations of MAMS trials and describes the characteristics of umbrella trials and basket trials. He discusses the BISCAY flowchart and the trial’s limitations and discusses the future of biomarker-based trial design in bladder cancer, citing two successful, meaningful biomarker-adaptive trials (PROOF 302 and IMvigor 011). Dr. Salmasi concludes by outlining future directions in the field, including ongoing trials for treatments for BCG-unresponsive NMIBC as well as neoadjuvant therapy for MIBC, where he asserts that work must be done to find the biomarkers of response, the need for improvements in molecular subtyping and treatment selection, and the need to identify optimal treatment. Finally, he asserts that improved patient outcomes would stem from an improved patient selection for radical cystectomy versus chemoradiation; there is also a need to continue to design adaptive trials to personalize treatment for those with metastatic urothelial cancer.

When is Radical Cystectomy Indicated for NMIBC?

by Guilherme Godoy, MD, MS | Mar 2022

Guilherme Godoy, MD, MPH, Assistant Professor of Urology at Baylor College of Medicine, in Houston, Texas, discusses the role of cystectomy in non-muscle invasive bladder cancer (NMIBC). He begins by describing the management options for NMIBC, including transurethral resection of the bladder tumor (TURBT), intravesical treatment, systemic therapy, and radical cystectomy. Dr. Godoy then explains the importance of re-TURBT, stating that it is one of the most critical steps in management for reducing understaging and improving intravesical therapy response in patients. He summarizes the indicators for cystectomy, including failure to resect, adverse pathology, and treatment failures. Dr. Godoy reviews data from a large single-institution retrospective study showing a significant difference in recurrence-free survival, cancer-specific survival, and overall survival in favor of the primary muscle invasion at presentation group vs. the progressive MIBC group. He then discusses data from a systematic review and meta-analysis of 14 studies on oncological outcomes of primary and secondary MIBC, finding worse outcomes overall for secondary muscle invasive cystectomy. Dr. Godoy looks at the European and AUA risk stratification tables, focusing on how both support aggressive management of high risk disease. He shows data from a study of the impact of variant histology on outcomes with intravesical immunotherapy, finding 40% progression-free survival compared to 17.5% in conventional bladder cancer. He states that all of this data supports cystectomy as an important and integral tool in the management of NMIBC due to its excellent oncological outcomes and potential benefit of abbreviated management and follow-up for aggressive NMIBC despite its morbidity, though the treatment may not be appropriate for everyone.