Resolving Discordant Results and Retesting Strategies in Lung Cancer

This segment focuses on one of the most challenging and clinically important aspects of precision oncology in lung cancer, which is how to manage situations when tissue based and liquid biopsy results do not align. Dr Husain and Dr Singhal explain that discordance between testing platforms is not uncommon and can occur for several reasons, including tumor heterogeneity, differences in sampling sites, and changes in tumor biology over time under treatment pressure. A tissue biopsy may capture one part of a tumor, while ctDNA reflects DNA shed from multiple tumor sites, which can lead to differences in what mutations are detected.

The panel discusses how clinicians approach these discrepancies in practice. Rather than relying on a single result, they emphasize the importance of integrating molecular findings with radiographic imaging, clinical symptoms, and the patient’s treatment history. When results conflict, repeat liquid biopsy may be used to track evolving molecular changes over time, while rebiopsy is considered when feasible and when the results are likely to change management. The experts highlight that longitudinal ctDNA monitoring can be especially helpful in revealing emerging resistance mechanisms that were not present or not detectable at the time of initial testing.

The discussion also covers how clinicians decide between repeating a blood test, performing another tissue biopsy, or relying on imaging to assess progression. Factors such as patient condition, tumor accessibility, and the urgency of making a treatment decision all play a role. This segment reinforces that genomic testing in lung cancer is an ongoing process rather than a one time event, and that thoughtful interpretation of evolving molecular data is essential for selecting the most appropriate next line of therapy.