# Circulating tumour DNA (ctDNA) as a predictor of progression-free and overall survival in non-resectable pancreatic cancer: a systematic review and meta-analysis

## TL;DR

This study reviews evidence showing that circulating tumor DNA (ctDNA) can predict survival outcomes in patients with non-resectable pancreatic cancer, but more standardized methods are needed for clinical use.

## Contribution

The study provides a meta-analysis showing strong prognostic value of ctDNA in non-resectable pancreatic cancer, highlighting the need for standardized thresholds.

## Key findings

- High baseline ctDNA levels are linked to shorter overall and progression-free survival.
- Unfavorable ctDNA changes during treatment are associated with worse survival outcomes.
- Many studies had high risk of bias due to methodological inconsistencies.

## Abstract

This systematic review and meta-analysis synthesised current evidence on circulating tumour DNA (ctDNA) for predicting clinical outcomes in patients with non-resectable pancreatic ductal adenocarcinoma (PDAC).

PubMed, Embase, and Cochrane databases were searched up to 31/01/2025. Eligible studies reported prognostic value of ctDNA in patients with non-resectable PDAC. Meta-analyses evaluated associations between baseline ctDNA and changes in ctDNA during treatment (ctDNA kinetics) and survival outcomes. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool.

Sixty-four studies involving 5652 patients with non-resectable PDAC were included, with 24 studies contributing to meta-analyses. High baseline ctDNA level implied shorter overall survival (OS; HR = 2.3, 95 % CI 1.9–2.8; n = 1883) and progression-free survival (PFS; HR = 2.1, 95 % CI 1.8–2.4; n = 1196). Unfavourable ctDNA kinetics were associated with shorter OS (HR = 3.1, 95 % CI 2.3–4.3; n = 269) and PFS (HR = 4.3, 95 % CI 2.6–7.2; n = 244). Thirty-three studies had high risk of bias in at least one QUIPS domain.

Baseline ctDNA and ctDNA kinetics demonstrate strong prognostic value in non-resectable PDAC. However, clinical translation is limited by methodological heterogeneity, notably the use of study-specific, non-validated thresholds. Standardised, externally validated thresholds for interpreting ctDNA changes are needed to support clinical implementation.

CRD42023438774.