Updates to Bladder Cancer Treatment Guidelines Offer Hope

After more than 30 years of relative stability, the treatment landscape for urothelial cancer has seen updates in recent years that provide hope for patients with the disease, according to news presented at the 2019 National Comprehensive Cancer Network (NCCN) Annual Conference.

At the conference, Thomas W. Flaig, M.D., spoke with CURE®’s sister publication, OncLive®, to discuss the latest therapeutic updates to be incorporated into the NCCN guidelines, including the addition of five new checkpoint inhibitors and new recommendations for patients with muscle-invasive bladder cancer.

“The biggest change in data in the bladder cancer guidelines occurred last year with the advent of checkpoint inhibitors,” said Flaig, professor and associate dean for clinical research, Genitourinary Cancer Program, Division of Medical Oncology, University of Colorado.

The integration of these drugs — including Keytruda (pembrolizumab) — expands the treatment spectrum for patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy.

“We finally have our foot in the door,” said Flaig. “We would be hard pressed to say what the developments were before that. Really, we would have said that we moved chemotherapies into different combinations, so this is a new class of highly effective drugs.”

Additionally, the updated NCCN recommendations include the use of cisplatin-based combination chemotherapy in patients with muscle-invasive bladder cancer, as well as chemotherapy plus radiation therapy.

Another major change was seen in 2017 in the disease’s staging guidelines, Flaig explained. “Based on the data we have for staging, based on the lymph node-only disease, those patients previously categorized as stage 4 disease could have a better prognosis, and in most cases, have a more aggressive therapy approach,” he said.

Given these updates, Flaig said that it is an optimistic time in bladder cancer. “For those of us who have been focused on this disease for a long time, we have been a bit discouraged by the lack of therapeutic progress over time,” he said. “(But) I’ve personally had several patients on checkpoint inhibitors with metastatic disease, which is essentially an incurable disease, and we are now reaching 1- and 2-year landmarks. It is certainly very heartening.”

The key, Flaig said, will be in examining the combination of checkpoint inhibitors to increase response rate in patients. Currently, when treated with one checkpoint inhibitor, response rates are in the 20% to 25% range, he explained. “What patients and the providers clearly want is durable responses that are well tolerated,” Flaig said. “We are seeing that now with checkpoint inhibitors, but the clinical trials that are underway right now are looking at combining checkpoint inhibitors, such as PD-1/PD-L1 inhibitors with CTLA-4 inhibitors or checkpoint inhibitors with chemotherapy. Those trials are underway, and many of us hope that they can give us a high response rate with similar durability over time.”