For patients with high-risk upper tract urothelial carcinoma (UTUC), a course of neoadjuvant chemotherapy before surgery can be very helpful: In fact, two recent clinical trials, including one led by medical oncologist Jean Hoffman-Censits, M.D., have shown that as many as 19 percent of patients achieve a pathologic complete response (no cancer found by the pathologist after surgery) in the primary tumor. However, more than 60 percent of patients do have some residual disease after neoadjuvant chemotherapy. What are the implications of residual disease after neoadjuvant chemotherapy? Brady resident Sean Fletcher, M.D., recently led a study to find out. In an analysis of nearly 2,000 patients who underwent radical nephroureterectomy for high-grade UTUC, those who had residual invasive (“non-responding”) disease after chemotherapy were found to have relatively poor survival outcomes.

“The extent of residual disease after chemotherapy is linked to how patients will fare,” notes urologist Nirmish Singla, M.D., senior author of the study, which was published in European Urology Oncology. “We need better ways of predicting who will respond to cisplatin-based chemotherapy so we can selectively offer it to those who will benefit from it. We also need to expand our clinical trial offerings to those who are less likely to respond to cisplatin.”

Immunotherapy may help

Looking for a better approach for patients who don’t respond to neoadjuvant chemotherapy, Hoffman-Censits is leading a multicenter, phase III clinical trial. Patients with high-risk, localized UTUC will be randomly assigned either to receive neoadjuvant chemotherapy alone or neoadjuvant chemotherapy combined with immunotherapy before surgery. Hoffman-Censits and Singla co-direct the UTUC Program and multidisciplinary clinic at Johns Hopkins.