What does this research mean for the field?

Ultrasensitive tumor-informed ctDNA MRD detection strongly predicts recurrence-free survival and identifies patients at high risk for metastatic relapse following resection of early-stage non-small cell lung cancer. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The aim is to evaluate the prognostic value of ultrasensitive ctDNA MRD detection for identifying metastatic relapse after resection of early-stage NSCLC.

May 29, 2026

Ultrasensitive tumor-informed ctDNA MRD detection to identify metastatic relapse and as predictor of recurrence-free survival following resection of early-stage NSCLC.

Key Points

The aim is to evaluate the prognostic value of ultrasensitive ctDNA MRD detection for identifying metastatic relapse after resection of early-stage NSCLC.
Patients with clinical stage I NSCLC were enrolled after curative resection.
Whole-genome sequencing generated personalized assays tracking somatic variants for MRD detection.
Plasma samples were analyzed at various time points, blinded to outcomes.
MRD detection prior to and after surgery was significantly associated with recurrence-free survival (HR 5.6, p=0.002).
97% of MRD-negative patients at 12 months were recurrence-free compared to 15% of MRD-positive patients (HR 48.3, p<0.0001).
MRD clearance post-adjuvant therapy was linked to improved recurrence-free survival (p=0.019).

Abstract

3060 Background: After curative-intent resection of non-small cell lung cancer (NSCLC), patients remain at risk for metastatic relapse and development of second primary malignancies. Circulating tumor DNA (ctDNA) molecular residual disease (MRD) detection has prognostic value, but sensitivity in early-stage disease has been limited. We evaluated an ultrasensitive tumor-informed whole-genome sequencing (WGS) assay that leverages phased variants (PVs) for longitudinal MRD detection in a cohort from the ctDNA Lung DETECT study (NCT05254782). Methods: Patients with clinical stage I NSCLC treated with upfront surgery were enrolled at Princess Margaret Cancer Centre/University Health Network. Resected tumor tissue underwent WGS to generate personalized tumor-informed assays tracking up to 5000 somatic variants, including prioritized PVs prioritized (CLARITY, Foresight Diagnostics). Plasma samples (pre-operative, 3-6 weeks post-operative landmark, 6 months, 12 months, and at recurrence) were analyzed retrospectively with labs blinded to outcomes. Endpoints were MRD detection, recurrence free survival (RFS), MRD clearance patterns. Results: Of 128 clinical stage I patients with banked samples, 121 (95%) had sufficient tumor for WGS. Pathologic stage distribution AJCC 8th Ed. was stage 0/I/II/III/IV (n=1/86/22/1). Among 121 patients, 16 (13%) experienced distant recurrence and 15 (12%) developed second primary malignancies: lung, breast, ovarian, prostate and sarcoma. MRD detection at pre-operative (HR 5.6, p=0.002) and post-operative landmark (HR 4.2, p=0.002) was significantly associated with RFS. MRD+ at 12 months post-resection demonstrated stronger prognostic value, as 97% (91/94) MRD-negative patients remained recurrence free compared to 15% (2/13) MRD+ patients (HR 48.3, p2 years after the last assessed sample. Conclusions: Ultrasensitive tumor-informed ctDNA MRD detection identifies patients at high risk for metastatic relapse following NSCLC resection, including pathologic Stage I, and may provide substantial lead time over conventional imaging. Clearance of post-surgical MRD with adjuvant therapy may inform post-resection surveillance and future studies of adjuvant therapy. Clinical trial information: NCT05254782 .

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