Abstract
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, with approximately 50% of patients experiencing recurrence within 1-year post-surgery. Very early recurrence (VER), defined as recurrence within 12 weeks, is an emerging concept. AIM: To investigate clinicopathological characteristics and predictive factors for VER in patients with PDAC. METHODS: A retrospective cohort study was conducted on 553 patients who underwent pancreatic surgery for PDAC at a single high-volume center between February 2019 and December 2024. Patients with VER (group 1, n = 28) were compared to those without (group 2, n = 251) after excluding 24 patients with inadequate surgical resection. Clinicopathological characteristics were compared using univariate and multivariate analyses, supplemented by random forest modeling to identify nonlinear patterns (P < 0.05). RESULTS: Group 1 patients were younger (65 ± 16.85 years vs 68 ± 9.58 years; P < 0.001) and had higher 6-month mortality (32.44% vs 14.77%; P = 0.032). Poorly differentiated tumors (G3) were the strongest predictor of VER (odds ratio = 2.43, 95% confidence interval: 0.88-5.34; P < 0.001, random forest feature importance: 0.35). Pancreatic head tumors (P = 0.031) and elevated red cell distribution width (P = 0.03) were associated with VER in univariate analysis. Sensitivity analysis confirmed imaging timing (4-8 weeks vs 8-12 weeks) did not significantly alter recurrence classification (P = 0.12). CONCLUSION: Poorly differentiated tumors are a key predictor of VER, linked to higher mortality. Machine learning enhances predictive accuracy, and molecular studies are needed to elucidate VER mechanisms. Tailored surveillance and multi-institutional validation are recommended.