Despite advances in early-stage lung cancer treatment, a significant number of patients experience disease recurrence after surgery or initial therapy.

A novel study has now demonstrated that a blood test (liquid biopsy) can reliably detect lingering lung cancer traces even in the earliest clinical stages, long before a tumour is large enough to show up on a scan.

This real-time genetic monitoring detailed in an article appearing in The Journal of Molecular Diagnostics, published by Elsevier, accurately predicts relapse risk, opening a critical window for timely, personalised therapeutic interventions.

Non–small-cell lung cancer (NSCLC) is the most common type of lung cancer and remains the major cause of cancer-related death.

Small tumours in patients with early-stage NSCLC (I to II) are usually surgically removed, and survival rates are reasonably high.

However, even in stage I, disease recurrence rates range between 5% and 19%, and imaging follow-up remains standard of care.

“As oncology shifts towards personalised risk-adapted care, liquid biopsies are emerging as a critical tool to bridge the gap between treatment completion and clinical recurrence,” explains lead investigator Matija Snuderl, MD, Department of Pathology, NYU Langone Health and Grossman School of Medicine, and Laura and Isaac Perlmutter Cancer Centre, New York, NY.

“In our study, we monitored patients with lung cancer across treatment stages using serial blood draws to track circulating tumour DNA (ctDNA) levels. By analysing tumour-specific signatures of ctDNA shed by tumour cells into the bloodstream, we evaluated how effectively liquid biopsy predicts relapse compared to standard imaging.”

The most significant finding was that a positive test result for tumour DNA served as a highly sensitive biomarker for minimal residual disease, detecting microscopic recurrence months before scans showed physical tumours, while a clear (negative) test strongly correlated with sustained remission.

“As a surgeon, I follow my patients very closely, and I want to know as soon as possible if the cancer has come back. Unfortunately, even the earliest stage patients risk recurrence,” notes co-lead investigator Harvey I.Pass, MD, Department of Cardiothoracic Surgery, NYU Langone Health, New York, NY.

“Our study’s findings highlight just how sensitive and specific liquid biopsy can be when integrated into routine post-treatment monitoring, even in the earliest stages of lung cancer. This is of critical importance for deciding on post-operative treatments.”

Dr. Snuderl adds, “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 personalise surveillance and intervention strategies for every individual patient."

The study highlights the implications of these blood tests for every stage of the patient journey:

• Clinicians can identify high- or low-risk patients far earlier.
• Test results help guide targeted treatment for patients with detectable residual disease, while potentially sparing those with clear test results from the burden of unnecessary overtreatment and toxicity.
• These liquid biopsies offer actionable clarity, reducing the anxiety of waiting between periodic imaging scans by replacing uncertainty with clear biological data.
• Early detection of relapse allows treatment to restart when the disease burden is extremely low, substantially improving long-term outcomes and survival prognosis.

The WGS liquid biopsy technology used in this study was developed by co-investigator Asaf Zviran, PhD, C2i Genomics Inc., New York, NY, who concludes, “The true promise of residual disease monitoring has always been to identify patients at high risk of recurrence early enough to enable curative intervention—before the cancer has an opportunity to spread, evolve, and diversify.”

Article: Predicting Recurrence of Stage IA Lung Adenocarcinoma Using Circulating Tumor Cell—Free DNA Whole-Genome Mutational Signatures

Source: Elsevier