New Findings on Tumor‑Informed ctDNA in Locally Advanced Rectal Cancer

In a multicenter retrospective analysis of 220 patients with stage II-III locally advanced rectal cancer, investigators observed that tumor-informative ctDNA status measured after neoadjuvant therapy (NAT) and again after resection tracked with recurrence outcomes in real-world practice.

ctDNA positivity at these post-treatment timepoints aligned with higher subsequent relapse risk, while ctDNA negativity aligned with more favorable observed courses.

Patients were grouped by management approach—NAT followed by surgery versus NAT followed by NOM—and ctDNA status was assessed in the relevant post-treatment windows, including serial sampling in the NOM setting. In the NOM cohort with post-NAT ctDNA available (n=64), 14 patients were ctDNA-positive; 13/14 had relapsed by the data cutoff, and the remaining 1/14 relapsed 8 months later (14/14 overall). Among the 50 ctDNA-negative patients, 5/50 experienced local recurrence. Post-NAT ctDNA positivity was also associated with inferior TME-free survival in a time-dependent analysis (HR 4.62, 95% CI 1.67–12.74; p=0.003). Among ctDNA-positive NOM patients who relapsed, the authors describe the pattern as predominantly local regrowth/local recurrence (92.9% local-only), with one case that included lung involvement alongside local relapse.

In surgically managed patients, ctDNA was evaluated during the post‑operative MRD window (defined as 2–12 weeks after surgery), and the authors report a marked separation in observed relapse rates (88.3% in ctDNA-positive vs 11.5% in ctDNA-negative; p<0.001). Investigators also report that postoperative ctDNA positivity was associated with substantially inferior disease-free survival in their analyses, consistent with ctDNA detection serving as a recurrence-associated marker in this cohort.

Key Takeaways:

• Within the NOM subgroup, post-NAT ctDNA positivity was associated with higher local regrowth/recurrence risk and worse TME-free survival than ctDNA negativity in this dataset.
• In the surgical subgroup, ctDNA positivity during the early postoperative assessment period was associated with substantially higher recurrence and inferior survival outcomes than ctDNA negativity.