138P Perioperative ctDNA and exosomal microRNA profiling in resectable perihilar cholangiocarcinoma: A comparative liquid biopsy study

Background: Surgery is the only potentially curative treatment for resectable perihilar cholangiocarcinoma; however, recurrence rates remain high and prognosis is poor.Although adjuvant systemic chemotherapy is routinely administered, reliable biomarkers to guide perioperative treatment decisions are lacking.Liquid biopsy approaches may enable dynamic assessment of molecular residual disease and help optimize treatment strategies.Methods: Between February 2022 and March 2025, 18 patients with resectable perihilar cholangiocarcinoma were prospectively enrolled.Plasma samples were collected preoperatively, postoperatively before adjuvant chemotherapy, and during adjuvant treatment.Circulating tumor DNA (ctDNA) was quantified using droplet digital polymerase chain reaction (ddPCR).Exosomes were isolated using a standardized workflow, and exosomal microRNA profiles were analysed by microRNA sequencing.KRAS, BRAF and IDH genes were screened, and mutation burden was calculated for each patient.Liquid biopsy parameters were correlated with diseasefree survival (DFS).Results: KRAS codon 12 mutations represented the most frequent genetic alteration.Analysis of ctDNA dynamics demonstrated that patients who remained serially ctDNA-negative had significantly longer DFS compared with patients with persistent ctDNA positivity (hazard ratio [HR] 6.7; p < 0.001) or those who converted to ctDNA positivity during adjuvant therapy (HR 5.8; p < 0.001).In contrast, exosomal microRNA profiles showed limited prognostic discrimination.Higher preoperative ctDNA mutation burden was associated with inferior outcomes under adjuvant therapy.During follow-up, four patients died. Conclusions:In resectable perihilar cholangiocarcinoma, perioperative ctDNA dynamics outperform exosomal microRNAs in risk stratification during adjuvant chemotherapy.Preoperative and longitudinal ctDNA assessment may support personalized perioperative treatment strategies, including identification of patients who may benefit from alternative approaches such as neoadjuvant therapy.