The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
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Black, J.R.M., Bartha, G. et al. Nature Medicine. 31: 70-76. (2025).
doi: 10.1038/s41591-024-03216-y.
Summary of the findings
Summary of the findingsTumour-node-metastasis (TNM) staging is an imperfect mechanism for stratifying patients with non-small cell lung cancer (NSCLC). Ultimately, this means that a subset of patients who will ultimately go onto relapse are not offered potentially curative adjuvant therapy, whilst unnecessary therapy is given to other patients who have in effect been cured by surgery. We used an ultra-sensitive circulating tumour DNA (ctDNA) detection assay to understand the degree to which pre-operative ctDNA detection might further stratify patients for clinical outcome. We studied ctDNA within 171 patients with early-stage NSCLC from the TRACERx study using a whole-genome sequencing-based tumour-informed assay that leveraged a median of 1,800 personalised variants per patient. This assay was capable of detections at between 1 and 3 parts per million (ppm) of ctDNA, and confirmed that pre-operative ctDNA detection in lung adenocarcinomas was strongly predictive of poor clinical outcome. Importantly, this effect was observed when analysis was restricted to tumours harbouring ctDNA at levels lower than could be reliably detected by the previous most sensitive assay studied in TRACERx. There, patients with ctDNA detected at below 80 ppm had worse progression-free and overall survival when compared to those in whom it was not detected.
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These findings suggest ctDNA detection assays might have an important future role when applied more widely to stratify patients for escalation or de-escalation of post-operative treatment. There is a need for prospective studies to study whether this technology, integrated into routine clinical care, can improve outcomes for patients identified for escalation of treatment as a result of ctDNA detection. In addition, further studies, including work currently being done in TRACERx, should seek establish the utility of post-operative monitoring and peri-treatment ctDNA kinetics using ultra-senstive approaches in understanding clinical outcomes and the dynamics of relapse.
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