Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies, with limited therapeutic options and poor prognosis. Dynamic contrast-enhanced imaging provides valuable non-invasive information on tumor biology, and rim enhancement (RE) on computed tomography (CT) or magnetic resonance imaging (MRI) has emerged as a potential biomarker of aggressive disease. To clarify its clinical significance, a systematic review and meta-analysis of studies published up to May 31st, 2025, in Medline, Scopus, Web of Science, and the Cochrane Library was conducted. Twelve studies (10 retrospective, 2 prospective) including 2207 patients were analyzed. The pooled prevalence of RE was 36.3%, with a good inter-observer agreement (κ = 0.808). RE was consistently associated with reduced resectability (odds ratio [OR] 3.35, 95% confidence interval [CI] 2.19-5.12, p < 0.001), poorer histological differentiation (OR 4.23, 95% CI 1.05-17.07, p = 0.043), and increased frequency of SMAD4 (OR 1.78, 95% CI 1.22-2.60, p = 0.003) and KRAS mutations (OR 2.55, 95% CI 1.37-4.75, p = 0.003). Patients with RE also experienced shorter progression-free, disease-free, and overall survival after both surgical and non-surgical treatments (all p < 0.001). These findings indicate that RE is a reproducible imaging marker of aggressive tumor biology in PDAC, reflecting unfavorable pathological and molecular features and serving as a predictor of resectability and survival.