A blood test using whole-genome sequencing (WGS) can predict lung cancer recurrence in patients with stage IA disease, potentially identifying residual cancer more than a year before it becomes visible on imaging, according to research published in The Journal of Molecular Diagnostics.
The findings suggest that circulating tumor DNA (ctDNA) analysis could improve postoperative surveillance and help identify patients who may benefit from additional treatment.
Although surgery is often curative for patients with stage IA lung adenocarcinoma, recurrence remains a concern. Current follow-up relies primarily on imaging, which may not detect disease until tumors have grown sufficiently to become visible.
Researchers at NYU Langone Health and C2i Genomics investigated whether WGS could detect molecular evidence of residual disease following surgery.
The retrospective study included 42 patients with stage IA lung adenocarcinoma, with 331 blood samples analyzed over the course of treatment and follow-up.
The researchers sequenced DNA from each patient's original tumor and matched normal tissue to establish an individual genetic fingerprint. They then used an artificial intelligence–supported algorithm to search for matching patterns in ctDNA extracted from blood samples collected during follow-up.
The approach predicted recurrence with 75 percent sensitivity and 83 percent specificity. Among 12 patients who experienced recurrence, nine had detectable ctDNA. In six of these patients, a positive ctDNA test predicted recurrence with a median lead time of 16.7 months before clinical or imaging confirmation.
Lead researcher MatijaSnuderl said, “Minimal residual disease testing via liquid biopsy represents a fundamental shift in post-operative care. It gives pathologists a powerful tool to diagnose disease before it appears on imaging and equips clinicians with actionable insights to personalize surveillance and intervention strategies for every individual patient.”
WGS also helped distinguish recurrent disease from a second primary lung tumor, a clinically important distinction that can be difficult to establish through conventional pathology alone.
Unlike targeted sequencing approaches, WGS examines mutations across the entire genome without requiring individually designed detection probes. This broader coverage may be particularly valuable in early-stage cancers, where circulating tumor DNA concentrations are extremely low.
However, the small, retrospective study requires prospective validation. Researchers also highlighted challenges involving sample collection, testing costs, and the use of routinely processed pathology specimens.
Further studies must establish how molecular monitoring should be integrated with imaging and whether earlier detection translates into improved patient outcomes.
Newsletters
Receive the latest pathologist news, personalities, education, and career development – weekly to your inbox.
