A panel of leading oncologists recently engaged in a critical discussion about the role of molecular testing and circulating tumor DNA (ctDNA) in managing muscle-invasive bladder cancer, revealing both the potential and current limitations of these emerging technologies.
Dr. Sumanta K. Pal led the discussion, exploring how clinicians currently utilize molecular testing in their practice. Most participants indicated they do not routinely order next-generation sequencing (NGS) or PD-L1 testing for all muscle-invasive bladder cancer patients, instead basing these decisions on specific clinical circumstances.
Current State of ctDNA Testing
The conversation highlighted particular interest in the Signatera ctDNA test, which analyzes genetic features from baseline tumor tissue to monitor for residual disease in blood samples. Dr. William E. Lee shared that he primarily uses Signatera to detect recurrence earlier than conventional scanning, though the clinical utility of this approach remains debated.
"The most powerful role is going to be if it has a predictive role for immunotherapy," Dr. Pal emphasized. He noted that while ctDNA testing might occasionally detect disease before imaging, such cases are "few and far between."
Emerging Clinical Trials
Several important clinical trials are investigating the clinical utility of ctDNA testing. The European IMvigor011 trial is examining ctDNA characteristics to guide immunotherapy decisions, potentially identifying patients who would benefit most from adjuvant treatment.
Additionally, an upcoming Alliance for Clinical Trials in Oncology study will evaluate adjuvant nivolumab allocation based on ctDNA status, with ctDNA-positive patients being randomized to receive either nivolumab alone or in combination with relatlimab.
Clinical Implementation Challenges
Dr. Spencer Shao raised a crucial question about whether earlier detection through ctDNA actually improves patient outcomes - a fundamental issue that remains unresolved. Dr. Pal acknowledged this limitation, stating, "I don't think we know that, from defining that early recurrence, we're ultimately leading to a superior outcome for the patient long term."
The experts agreed that while ctDNA testing shows promise, its most valuable application may be in helping clinicians make decisions about escalating or de-escalating therapy, rather than as a replacement for conventional imaging. Until more definitive evidence emerges, many practitioners prefer to use ctDNA testing primarily in the context of clinical trials.
Future Directions
The field is evolving rapidly, with new bespoke assays in development that may examine hundreds of genetic alterations. However, experts caution that increased sensitivity might lead to detection of non-meaningful minimal residual disease, highlighting the need for careful validation of these technologies.
As the oncology community awaits results from ongoing trials, the consensus appears to be that while ctDNA testing holds promise, its routine clinical implementation requires more substantial evidence demonstrating improved patient outcomes.
