Bladder Cancer: Genomics May Predict Benefit from Neoadjuvant Chemotherapy

ORLANDO – At the 2017 Genitourinary Cancers Symposium, David J. McConkey, MD, PhD, director of Johns Hopkins Greenberg Bladder Cancer Institute in Baltimore, Maryland, described how genomics can affect the clinical management of patients with bladder cancer.¹

In this keynote lecture, Dr McConkey discussed the studies that identified molecular subtypes of bladder cancer. The Cancer Genomic Atlas (TCGA) study, for example, identified clusters I, II, III, and IV, or luminal I, luminal II, basal I, and basal II muscle-invasive bladder cancers.

“There are some diagnostic challenges to identifying the histopathological variants of bladder cancers and this is where we think genomics can play a role,” Dr McConkey explained. “Distinct biological properties probably warrant different therapies. We suspect that by using both RNA and DNA sequencing, we can help make more accurate diagnoses.”

With the use of neoadjuvant chemotherapy, approximately 40% of tumors are downstaged to pT2 or better. Downstaging to pT0 or pT2 or better is associated with excellent clinical outcomes. Dr McConkey discussed the recent work that indicates that DNA damage repair (DDR) mutations and disease subtype are associated with clinical benefit from neoadjuvant chemotherapy in bladder cancers.

A study that Dr McConkey and colleagues conducted showed that patients with basal cancers treated with neoadjuvant chemotherapy achieved better outcomes than those who received no chemotherapy.

“I’m very excited about this research,” said Dr McConkey. “I think that the clinical trials evaluating the relationship between DDR mutations and outcomes with neoadjuvant chemotherapy are really going to have transformative impact on our field with regard to bladder preservation.”

Reference

1. McConkey DJ. Emerging impact of genomics on the clinical management of bladder cancer. Lecture presented at: 2017 Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.