Background

Bladder cancer is one of the most common cancers in the United States. In 2015, about 75,000 new cases were diagnosed. Most people are diagnosed when the cancer is still at an early stage, and surgery to remove the tumor is often enough to cure them. However, about one out of every four patients is diagnosed with a more serious form called muscle-invasive bladder cancer (MIBC). This means the cancer has spread into the bladder wall and is harder to treat. 

The standard treatment for MIBC has usually been chemotherapy followed by surgery to remove the entire bladder. Another option, called combined modality therapy (CMT), uses chemotherapy and radiation instead of bladder removal. CMT gives patients a chance to keep their bladder while still aiming for the same chance of cure. 

What This Research Proposes to Address

Recent scientific advances allow researchers to study the DNA of cancer cells in detail. These studies have shown that bladder cancers can be divided into groups based on their genetic “makeup.” These groups behave differently, but so far, this information hasn’t been used to guide treatment because more proof is needed. 

In this project, researchers used new genetic tools to study a large group of patients with MIBC who were treated with CMT. They looked closely at the tumor DNA and compared it with detailed medical records, such as how well the tumors responded to treatment and how the patients did over time. 

Why This Research Is Important

By connecting the genetic changes in tumors with how patients responded to treatment, the researchers hoped to identify patterns. These patterns, called biomarkers, could help doctors predict which patients are most likely to benefit from CMT and who might need other approaches. 

If successful, this work will give doctors better tools to personalize treatment for people with MIBC. Instead of relying only on standard methods, doctors could use genetic information to choose the most effective therapy for each patient. This would improve outcomes and may also help more patients keep their bladder while still beating cancer. 

Final Report Summary

Researchers now know a lot more about the genetic makeup of muscle-invasive bladder cancer (MIBC), but it has been hard to turn that knowledge into better treatments for patients. Most genetic studies so far have focused on people who had their bladder removed as part of treatment. This means we don’t know as much about how tumor genetics affect people who try a bladder-sparing approach called combined modality therapy (CMT), which uses both chemotherapy and radiation. 

In this project, scientists studied the DNA and activity of tumors from a large group of patients with MIBC who were treated with CMT. They compared tumor genetics with how well patients responded to treatment and how they did over time. 

Their research suggests that not all MIBC tumors respond to CMT in the same way. Different molecular subtypes of bladder cancer appear to react differently to this treatment, and these differences are not the same as what has been seen in patients who had bladder removal. This work could help doctors better match patients to the right treatment and improve chances of success while preserving the bladder. 

Mouw K. W. (2017). DNA Repair Pathway Alterations in Bladder Cancer. Cancers, 9(4), 28. https://doi.org/10.3390/cancers9040028

Giacalone, N. J., Shipley, W. U., Clayman, R. H., Niemierko, A., Drumm, M., Heney, N. M., Michaelson, M. D., Lee, R. J., Saylor, P. J., Wszolek, M. F., Feldman, A. S., Dahl, D. M., Zietman, A. L., & Efstathiou, J. A. (2017). Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience. European urology, 71(6), 952–960. https://doi.org/10.1016/j.eururo.2016.12.020

Mouw, K. W., Goldberg, M. S., Konstantinopoulos, P. A., & D’Andrea, A. D. (2017). DNA Damage and Repair Biomarkers of Immunotherapy Response. Cancer discovery, 7(7), 675–693. https://doi.org/10.1158/2159-8290.CD-17-022

None Reported as of August 2025

NA