Rectal Cancer After TNT: BJS Open | October 2026

What Did the Study Find?

This meta-analysis included 6 studies involving 597 patients with locally advanced rectal cancer undergoing total neoadjuvant therapy (TNT), evaluating whether circulating tumour DNA (ctDNA) could predict complete clinical response (cCR) and local tumour regrowth.

• Post-TNT ctDNA negativity was strongly associated with cCR (OR 8.01; 95% CI 1.43–44.90).
• However, ctDNA negativity did not reliably predict sustained cCR (OR 3.46; 95% CI 0.03–394.64), with substantial uncertainty.
• Persistent ctDNA positivity was associated with worse disease-free, distant recurrence-free and progression-free survival.
• ctDNA demonstrated high specificity and positive predictive value for residual disease, making a positive result clinically concerning.
• Crucially, sensitivity for residual local disease and regrowth was low.
• A substantial proportion of patients with residual rectal tumours remained ctDNA-negative at restaging.

Why Does It Matter?

The increasing adoption of watch-and-wait organ preservation after TNT makes accurate identification of complete response essential.

Although ctDNA offers valuable information about molecular residual disease and systemic recurrence risk, small residual rectal tumours may shed insufficient DNA into the circulation to be detected.

Consequently, a negative liquid biopsy cannot safely establish that the primary tumour has disappeared.

GastroAGI Takeaway

In rectal cancer, ctDNA positivity is a warning signal—but ctDNA negativity is not a green light for organ preservation.

The study supports ctDNA as a complementary biomarker for systemic oncological risk, not a replacement for the established response-assessment triad:

High-resolution pelvic MRI + endoscopy + digital rectal examination.

Patients should not be selected for watch-and-wait management solely because ctDNA is undetectable.