Prognostic impact of circulating tumor DNA in pancreatic ductal adenocarcinoma: A meta-analysis.

e16430 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy and the third leading cause of cancer-related death in the US, with poor prognosis across stages. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker. This systematic review and meta-analysis evaluates the prognostic impact of baseline (pre-treatment) ctDNA status on progression-free survival (PFS) and overall survival (OS) in PDAC. Methods: We systematically searched major databases for studies assessing baseline ctDNA status before treatment in PDAC patients. PFS was reported in eight studies, OS in 14 (seven overlapping). Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses stratified by disease stage (localized/resectable vs. advanced/metastatic). Heterogeneity was assessed via I² statistic. Results: A total of 1,050 PDAC patients (median age 69.9 years, range 34–87.3) were included: 482 with resectable/localized disease, 568 with advanced/metastatic. Undetectable baseline ctDNA was reported in 520 patients. Pooled median PFS/HRs showed detectable ctDNA associated with significantly worse PFS across eight studies (HR 2.11, 95% CI 1.72–2.60; low heterogeneity). Subgroup analysis confirmed similar impact in resectable (HR 2.11, 95% CI 1.72–2.60) and advanced disease (HR 2.11, 95% CI 1.64–2.72). Detectable baseline ctDNA was also associated with inferior OS across 14 studies (pooled HR 2.23, 95% CI 1.80–2.77; I² = 0%). Subgroup analyses demonstrated consistent poorer OS in resectable disease (HR 2.36, 95% CI 1.37–4.08; I² = 0%) and advanced disease (HR 2.23, 95% CI 1.72–2.89; I² = 20.8%). Conclusions: Baseline ctDNA positivity is strongly associated with inferior PFS and OS in PDAC, independent of disease stage, with low heterogeneity across studies. These findings underscore ctDNA as a robust, stage-agnostic prognostic biomarker and support its integration into clinical practice for improved risk stratification, treatment personalization, and potential guidance of adjuvant/neoadjuvant strategies. Prospective validation and standardization of ctDNA assays are warranted.