ctDNA as a predictor of outcome after curative resection for locally advanced rectal cancer: systematic review and meta-analysis

Ahmed Nassar ^1,2, Noha E Aly ², Zhaohui Jin ³

⁰University of Aberdeen, Aberdeen, Scotland, UK.

Colorectal Disease : the Official Journal of the Association of Coloproctology of Great Britain and Ireland +

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May 28, 2024

View abstract on PubMed

Summary

Circulating tumor DNA (ctDNA) levels after neoadjuvant treatment predict distant metastasis and relapse in locally advanced rectal cancer (LARC). ctDNA status did not predict pathological complete response (pCR).

Area Of Science

Oncology
Molecular Diagnostics
Rectal Cancer Research

Background

Locally advanced rectal cancer (LARC) management involves neoadjuvant treatment followed by surgical resection.
Monitoring treatment response and predicting prognosis are crucial for optimizing patient outcomes.
Circulating tumor DNA (ctDNA) is an emerging biomarker for cancer detection and monitoring.

Purpose Of The Study

To evaluate the predictive value of ctDNA measurements at various time points for treatment response and prognosis in LARC patients.
To assess if ctDNA can identify patients at higher risk of distant metastasis and disease relapse after neoadjuvant therapy and surgery.

Main Methods

A systematic review and meta-analysis of randomized controlled trials and observational studies.
Search of major databases (MEDLINE, Embase, Cochrane) for studies published from 1946 to January 2024.
Inclusion of studies comparing outcomes between ctDNA-positive and ctDNA-negative LARC patients undergoing neoadjuvant treatment.

Main Results

Analysis of data from 1022 patients revealed that ctDNA positivity preoperatively and postoperatively significantly increased the risk of distant metastasis (5.03x and 6.17x, respectively).
ctDNA status did not show a significant association with achieving pathological complete response (pCR).
Patients with positive ctDNA preoperatively and postoperatively had a substantially higher risk of overall disease relapse (13.55x and 12.14x, respectively).

Conclusions

ctDNA measurement holds potential for guiding treatment and follow-up strategies in LARC.
ctDNA can identify high-risk patients prone to disease relapse, enabling personalized surveillance and therapeutic approaches.
Further prospective studies are recommended to standardize ctDNA analysis and application in clinical practice.

Keywords:

advanced circulating DNA ctDNA rectal cancer