Present, future bladder cancer tests
Molecular testing in bladder cancer is limited at this time, according to Dr. Lotan.
“Most people use urine cytology. Some people use UroVysion, which is a FISH [fluorescence in situ hybridization] assay for patients who have atypical cytology. It is a genetic marker looking for chromosomal abnormalities in cells in the urine. It probably should be used selectively, if at all,” he said. Additional diagnostic urine tests for recurrent bladder cancer are BTA STAT, BTA TRAK, and NMP22.
Another available group of tests is the CxBladder (Pacific Edge), which combines biomarker genes with known bladder cancer risk factors to help rule out cancer in patients with hematuria. (Also see, “Bladder cancer biomarker test accurately adjudicates atypical cytology.")
“It is currently used by some people to help with surveillance or detection in patients with hematuria. There are several studies that show it has improved sensitivity over cytology. There are still some issues with how exactly to incorporate these markers clinically, and there’s some concern over risk of false-positive results,” said Dr. Lotan, who was among the researchers to study CxBladder.
Dr. Lotan estimates there are 20 to 30 markers in development for bladder cancer detection or surveillance that have yet to be validated. This includes the UroSEEK test, developed by Johns Hopkins researchers, which detects DNA mutations identified with urothelial cancers in urine samples.
Dr. Lotan continues to study the Decipher Bladder test, a genetic test aimed at classifying muscle-invasive bladder cancer’s molecular subtype. This test may help determine which patients might benefit from neoadjuvant chemotherapy before radical cystectomy or accurate staging of the disease.
“There is still some validation that needs to be done before the Decipher test should be used routinely,” Dr. Lotan said.
In fact, there are multiple trials using biomarkers looking to predict which patients would and would not likely response to chemotherapy, according to Dr. Lotan.
“There is significant interest in trials that are trying to identify patients who are highly likely to respond with the hope that they may be enrolled and spare their bladder,” he said. “There is also interest in identifying which patients might have micrometastatic disease after the bladder is removed so they may get adjuvant therapy.”
Understand before you educate
Dr. Lotan said it’s important for urologists and other providers to validate clinical benefits before using any genetic testing.
“It’s important to know what the goals of the test are and how it would change management of the patient. For many markers, it’s not yet clear how they would change management. While they provide additional information over clinical information alone, sometimes that information doesn’t tell you exactly what to do and in many cases it can lead to anxiety and added costs,” he said.
Pursuing more targeted treatment for bladder cancer is one of many areas of study to optimize bladder cancer treatment, according to Dr. Plimack.
“I think we’re looking at every angle we can,” she said. “We’ve looked at immunotherapy and harnessing the immune system. There is cellular therapy on the horizon for urothelial cancer, with engineered T-cell therapy. There is standard targeted therapy like erdafitinib. There’s targeted chemotherapy with enfortumab vedotin, an antibody drug conjugate where the antibody is tagged to the target on the tumor cell but the conjugate is a chemo drug. And we’re still refining how we give regular chemotherapy and whether to give it in combination versus separately.”
Dr. Siefker-Radtke has consulting and advisory ties with Janssen, Merck, NCCN, Bristol-Myers Squibb, AstraZeneca, BioClin Therapeutics (Rainier Therapeutics), Bavarian Nordic, Seattle Genetics, Nektar, Genentech, Inovio Pharmaceuticals, and EMD Serono. She receives research funding from NIH, Michael and Sherry Sutton Fund for Urothelial Cancer, Janssen, Takeda, Bristol-Myers Squibb, BioClin Therapeutics, Nektar and Merck. Dr. Lotan reports that in the last 2 years he has: consulted, advised, and/or conducted research for Abbott, Pacific Edge, FKD Therapies Oy, BioCanCell, Decipher Biosciences, Cepheid, AstraZeneca, Merck, MDxHealth, Photocure, Ferring, and CAPS Medical; served on the data safety monitoring board for Urogen and Synergo; and held a leadership position with Vessi Medical. Dr. Konety is a clinical trial investigator for Merck, Pacific Edge, Photocure, FKD Therapies Oy, and Bristol-Myers Squibb. He has consulted for Ferring, Photocure, and Nucleix. Dr. Plimack is a scientific advisor for Bristol-Myers Squibb, Flatiron, Genentech, Merck, Seattle Genetics; does data safety monitoring for AstraZeneca and Pfizer; and receives grants for clinical research from Astellas, Bristol-Myers Squibb, Genentech, Merck, Peloton, Pfizer, and AstraZeneca.