Genomic Profiling May Translate to Personalized Treatment for Bladder Cancer Subtypes

Researchers at Baylor College of Medicine found that treating advanced bladder cancer is not a one-size-fits-all solution when they discovered 11 patients with a neuronal subtype of the disease responded to immunotherapy.

"We were able to show that mutation signatures, molecular subtypes, load of new cancer-associated molecules and known clinical and pathological factors have a very clear influence on overall patient survival. But, how can we apply this knowledge into clinical practice?” Dr. Seth Paul Lerner, who is the director of urologic oncology and of the Multidisciplinary Bladder Cancer Program at Baylor College of Medicine, said in a press release.

"Bladder cancer causes an estimated 160,000 deaths worldwide per year and we are behind other cancer fields in terms of the clinical applications of its molecular data and biology," he added. "However, we can begin to see how we can use this information in the future to provide the best treatment for each patient."

As part of the Cancer Genome Atlas Research Network group, the researchers reported the different survival outcomes of five expression-based cancer subtypes — one being the neuronal subtype, which has a very distinct expression profile and is associated with poor survival and less favorable outcomes. According to the National Cancer Institute, the neuronal subtype may behave similarly to neuroendocrine neoplasms (that arise from cells of the endocrine and nervous systems) of other tissue sites and may respond to etoposide-cisplatin therapy — but not always.

"One of the challenges that we have when taking care of patients with bladder cancer is that from one patient to the next, the prognosis, the stage and the response to different kinds of treatment differ," said Lerner, who is also a professor of urology and the Beth and Dave Swalm Chair in Urologic Oncology. "The diverse cancer characteristics pose a challenge when selecting the best treatment for each patient."

The researchers developed a computational tool, or a single-patient classifier, for bladder cancer RNA expression, “that effectively enables physicians to assign a bladder cancer subtype to an individual patient's cancer using that patient's genomic data," explained first author Dr. Jaegil Kim, who was at the Broad Institute at the time he was working on this project and currently is a senior principal scientist at Tesaro.

They then applied the tool to findings from the phase 2 IMvigor210 trial — designed to investigate the clinical activity of Tecentriq (atezolizumab) in metastatic urothelial cancer.

Of the 11 patients identified with a neuronal subtype, the researchers found a 100% response rate in eight confirmed cases — including two complete responses and six partial responses – and a 72% overall response rate – including three patients with an unconfirmed response.

"This translated to a very high survival probability which is unprecedented in advanced bladder cancer," Lerner said. "Although this is a small group of patients, it is very exciting to see that our basic research can be directly translated to the clinical setting allowing us to determine which subtype of bladder cancer has a better chance to respond well to a specific treatment."