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

Joshua J. Meeks, MD, PhD
Published: Monday, Nov 05, 2018



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, 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.

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TitleExpiration DateCME Credits
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
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