Some people respond well to neoadjuvant chemotherapy, but others don’t

Some people who have muscle-invasive bladder cancer do better if they receive cisplatin-based neoadjuvant chemotherapy before radical cystectomy, surgery to remove the bladder. The problem: the chemotherapy works very well in some people, and not so well in others. “Clinical trials have shown that patients who respond to chemotherapy before radical cystectomy are more likely to be cured,” says Trinity Bivalacqua, M.D., Ph.D., the R. Christian B. Evensen Professor of Urology and Director of Urologic Oncology. “But other people may do better with alternative treatments such as immunotherapy, so we need to be able to predict which patients will benefit from neoadjuvant chemotherapy.”

They may have found a way to point patients toward the treatment that will help them most: Recently, Bivalacqua and pathologist Alex Baras, M.D., Ph.D., analyzed biopsy tissue from Johns Hopkins patients with muscle-invasive bladder tissue. They found that a measurement called “tumor infiltrating (TIL) density” was strongly correlated with an important immune system factor, a “checkpoint inhibitor” called PD-L1. “Intriguingly, our findings suggest that the immune system plays an important role in how the bladder responds to chemotherapy.” T-cells are great warriors in the immune system that attack cells the body perceives as the enemy. “We found a strong link between the ratio of T-cells (CD8) to Regulatory T cells TIL densities and the response to chemotherapy.” This work, published in Oncoimmunology, represents the first report in bladder cancer showing that this ratio can predict who will respond well to neoadjuvant chemotherapy; combined with other genetic information about a patient’s particular tumor, this information “will help us guide patients to the treatments that will work best for them.”