Joshua J. Meeks, MD, PhD, discusses effectively implementing recent therapeutic advances across the disease continuum of bladder cancer.

Dr Meeks on Harnessing Innovation in Bladder Cancer

Joshua J. Meeks, MD, PhD, the Edward M. Schaeffer, MD, PhD, Professor of Urology and an 

associate professor of Urology and Biochemistry and Molecular Genetics at Northwestern University Feinberg School of Medicine, discusses key takeaways from a session that he participated in during the 

2024 American Urological Association Annual Meeting

 regarding effectively implementing recent therapeutic advances across the disease continuum of bladder cancer.

Meeks begins by noting that innovation had made it an especially exciting time in the bladder cancer treatment landscape, especially in terms of the treatment of patients with non­–muscle-invasive bladder cancer (NMIBC) due to the rapidly increasing number of therapeutic options. Bacillus Calmette-Guerin (BCG) worked well for patients for a time, but due to the shortage of the agent that occurred in 2020 investigators were forced to develop new technologies and therapeutics for the treatment of patients with NMIBC, Meeks explains.

During the plenary session of the meeting, investigators presented findings from multiple phase 2 studies examining therapies in NMIBC that produced overall response rates (ORRs) ranging from approximately 60% to 80%, which represented a significant improvement over previously available treatments that conferred ORRs of approximately 15% to 30%, Meeks says. In the past, if an agent produced an ORR of approximately 30% it was likely to be reviewed by the FDA and now with response rates exceeding twice that figure, it’s an exciting time for patients and clinicians alike, Meeks notes.

Now that treatment options have expanded from 1 to more than 5, clinicians have the opportunity to work with patients and other members of the care team to determine what the best option is for a patient and offer personalized care, Meeks says. Factors that should be weighed when selecting the best treatment option include economics and travel burden, and there are additional therapeutics on the horizon that could expand choices for patients even further, Meeks concludes.

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Joshua J. Meeks, MD, PhD, assistant professor of urology, Northwestern University Feinberg School of Medicine, discusses the importance of 

 is not a biomarker, although it is present in over 70% of muscle-invasive tumors, says Meeks. The same frequency is found in patients with T1 tumors. 

 plays an integral role in bladder cancer. As was reflected in genetic models in mice, it was discovered that a patient is going to lose 

 and Rb1 expression in almost all of these tumors.

As the field progresses, subtypes will become more prominent, explains Meeks. Currently, the 5 subtypes are luminal papillary, true luminal, luminal-infiltrated, basal, and neuronal. As physicians uncover more about these tumors, subtyping will become more important to the prognostication and prediction of certain therapies—both chemotherapy and immunotherapy, he concludes.

Joshua J. Meeks, MD, PhD, assistant professor of urology, Northwestern University Feinberg School of Medicine, discusses the importance of p53 and Rb1 in bladder cancer.

Dr. Meeks on the Importance of p53 and Rb1 in Bladder Cancer

Joshua J. Meeks, MD, PhD, assistant professor of urology, Northwestern University Feinberg School of Medicine, discusses the mutations associated with T1 progression in bladder cancer.

Patients with T1 progression are difficult to treat, explains Meeks. Patients are beginning to understand that T1 tumors are complex and are rarely treated effectively with Bacillus Calmette-Guérin (BCG). These are very aggressive cancers that may potentially become muscle-invasive bladder cancers. In all-comers, one-third of these patients will not be alive at 3 years, and 15% will succumb to bladder cancer, notes Meeks. Therefore, many physicians are asking if there is any way, from a molecular perspective, to determine the “bad actor.”

Physicians compared these patient’s mutation profiles. Though they were not able to isolate a particular mutation, Meeks explains that tumor mutational burden (TMB) matters. Those who received BCG and responded had a higher TMB than nonresponders. That parallels the immunotherapy data showing that patients with higher TMB tend to respond, states Meeks. At progression, TMB was lost. Therefore, physicians believe that is an escape mechanism that the cancer is using.

Joshua J. Meeks, MD, PhD

Articles

Dr Meeks on Harnessing Innovation in Bladder Cancer

Dr. Meeks on the Importance of p53 and Rb1 in Bladder Cancer

Dr. Meeks on Mutations Associated With T1 Progression in Bladder Cancer