753 Background: Circulating tumor DNA (ctDNA)–based minimal residual disease (MRD) testing has emerged as a powerful prognostic tool in solid tumors and may inform postoperative management. We evaluated the prognostic significance of ctDNA MRD monitoring in patients with pancreatic cancer (PC) undergoing curative resection followed by adjuvant FOLFIRINOX. Methods: Between Oct 2023 and Feb 2025, patients with resected PC receiving adjuvant FOLFIRINOX were prospectively enrolled from 11 hospitals in Korea. Whole blood (20 mL) was collected at up to seven postoperative time points 4 (P1), 12 (P12), 24 (P24), 40 (P40), 56 (P56), 72 (P72), and 88 (P88) weeks and analyzed with a tumor-informed assay (CancerDetect, IMBdx). MRD positivity was defined as detection of ≥2 mutations. Results: Eighty-six of 92 enrolled patients were included (median age 68, range 42–82; 49% male). Pathologic stages were I (39.5%), II (46.5%), III (12.8%), and IV (1.1%). Postoperative MRD positivity at P1 was 31.3%, increasing with stage (15.2% I, 34.8% II, 54.5% III–IV; P for trend = 0.003). At a median follow-up of 13.0 months, 20 patients (23.3%) had recurred. While stage, T, and N classifications were not associated with disease-free survival (DFS), MRD positivity at P1 predicted inferior DFS HR 5.31; 95% CI 2.1-13.4; P <0.001; 1-year DFS 56.0% vs. 92.8%. Stage-stratified analysis showed prognostic significance for stage I (HR 8.90, P <0.001; 1-year DFS 40.0% vs. 92.9%) and stage II (HR 6.87, P = 0.02; 1-year DFS 64.3% vs. 95.6%), but not for stage III/IV (HR 2.02, P = 0.45). Longitudinally, MRD persisters had the worst outcomes (HR 21.17, P<0.001; 1-year DFS 25.0%), followed by positive converters (HR 4.30, P = 0.045; 1-year DFS 85.7%) and negative converters (HR 3.87, P = 0.033; 1-year DFS 73.7%), compared with negative persisters (1-year DFS 94.2%). Conclusions: Postoperative ctDNA MRD detection strongly predicted recurrence in resected PC treated with adjuvant FOLFIRINOX. Longitudinal MRD dynamics correlated with treatment response and recurrence risk, supporting the clinical utility of MRD to inform postoperative surveillance and therapeutic strategies.
Hong et al. (Sat,) studied this question.