Prognostic and Predictive Role of Circulating Tumor DNA in Locally Advanced Rectal Cancer Managed With Total
Faizan Bashir1, Qurat-Ul-Aine Bhat1, Jayden Allegakoen2
1School of Medicine Shiraz University of Medical Sciences Shiraz Iran.
Health Science Reports
|July 29, 2026
Summary
Clearance of circulating tumor DNA (ctDNA) after total neoadjuvant therapy (TNT) in rectal cancer may predict treatment response. However, ctDNA sensitivity is limited for guiding non-operative management.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Circulating tumor DNA (ctDNA) is a key biomarker for tumor burden and minimal residual disease.
- Total neoadjuvant therapy (TNT) is increasingly used for organ-preserving strategies in locally advanced rectal cancer (LARC).
- Reliable markers of treatment response are crucial for LARC management.
Purpose of the Study:
- To evaluate the prognostic and predictive value of ctDNA in patients with LARC undergoing TNT.
- To assess ctDNA's utility in predicting treatment response and recurrence risk.
Main Methods:
- Systematic review of studies evaluating ctDNA during or after TNT in LARC.
- PRISMA guidelines were followed for study selection.
- Searches were conducted across major scientific databases.
Main Results:
- Baseline ctDNA was nearly universal but not discriminatory.
- Post-TNT ctDNA negativity correlated with complete response.
- Persistent ctDNA predicted residual disease and inferior survival.
- Post-TNT ctDNA showed high specificity but low sensitivity for residual disease.
Conclusions:
- ctDNA clearance post-TNT may indicate treatment response and lower recurrence risk.
- Current data are limited by small, heterogeneous cohorts and variable assays.
- ctDNA's sensitivity is insufficient for standalone use in non-operative management selection.