Good enough?

The annual American Society of Clinical Oncology (ASCO) meeting typically showcases paradigm-changing clinical advances and the 2023 ASCO meeting was no exception. Presentations on overall survival (OS) in early-stage EGFR-mutated lung cancer patients treated with adjuvant Osmeritinib (ADAURA trial) and progression free survival (PFS) in grade 2 IDH1/2-mutated glioma patients with recurrent/residual disease treated with the IDH inhibitor Vorasidenib (INDIGO trial) were particularly impressive. They highlight the importance of personalized approaches to cancer treatment. 

Also presented at ASCO 2023 were numerous advances in testing technologies and molecular diagnostics. The field continues to push the boundaries of what is considered possible. Liquid biopsy-based approaches to tumor genetic analysis continue to mature and tests that would have been considered unthinkable a few years ago are routine today. These are amazing advances indeed. But one application of liquid biopsy technology caught my eye for what it didn’t show. 

A study by a consortium of investigators and institutions in the UK used a commercially available early cancer detection liquid biopsy laboratory developed test (LDT) to evaluate over 6000 individuals without a cancer diagnosis referred for new symptoms suspicious for cancer. The ability of the test to detect a cancer signal was compared to a standard diagnostic workup comprising routine modalities such as imaging and endoscopy performed on the same patients. On the surface, the results were intriguing and demonstrated a negative predictive value (NPV) of 97.6%. But a deeper look showed that a significant percentage of patients who were positive for a cancer signal by the liquid biopsy test, around 24%, did not have any clinical evidence of cancer found during their routine clinical workup. This raises some thorny questions.

Are these truly false positive results? Will these individuals go on to develop cancer in the near-future due to sub-detectable (via imaging/endoscopy) occult tumors? How should they be clinically surveilled? Is the anxiety inevitably experienced by those in this situation worth the clinical benefit (if any)? Is this level of performance adding anything to clinical management? And this was in a symptomatic patient population. Would the false positive rate be higher in an asymptomatic population? 

This clinical conundrum, namely the significance of an apparent false positive result from an early cancer detection screening test, highlights the types of novel scenarios that arise as new testing technologies advance. Future studies will likely yield significant insight here and overall the findings are promising. But we should all remember the most important question – Is this good enough for patients? 

Written by Todd W. Kelley, MD, Executive Director of Medical Affairs

About Biofidelity

Founded in 2019, Biofidelity is a rapidly growing private company of scientists, engineers, physicians, and commercial experts dedicated to making genomics globally accessible. Our goal is to enable millions of lives to be transformed through access to vital information needed for accurate targeting and monitoring of cancer treatment. We are achieving this by developing innovative technologies that unleash the potential of genomics by removing the noise from genomic data, providing only the information needed to enable swift decision-making.

Learn more about Biofidelity at https://biofidelity.com