Effectiveness of circulating tumor cells and circulating tumor DNA in peritoneal lavage fluid for predicting metachronous peritoneal metastasis of gastric cancer.

BACKGROUND

Peritoneal metastasis is a leading cause of death in gastric cancer (GC) patients, highlighting the need for early diagnosis and high-risk population identification. While circulating tumor DNA(ctDNA) and circulating tumor cells (CTC) have been widely studied in blood, their role in peritoneal lavage fluid (PLF) remains unexplored.

METHODS

Patients with stage III GC were enrolled, and preoperative/postoperative PLF was collected in this study. ctDNA in PLF supernatant was analyzed via next-generation sequencing (NGS), while CTC in the pellet were detected using Epithelial Cell Adhesion Molecule (EpCAM), Folate Receptor (FR), and Cytokeratin (CK) immunofluorescence.

RESULTS

ctDNA-positive patients had higher peritoneal metastasis risk (preoperative HR: 4.82, 95% CI 1.03-22.54, p = 0.04; postoperative HR: 4.83, 95% CI 1.03-22.54, p = 0.04). CTC-positive patients also showed higher risk (preoperative HR: 6.76, 95% CI 0.92-49.74, p = 0.003; postoperative HR: 7.41, 95% CI 1.67-32.87, p = 0.02). Postoperative ctDNA had higher predictive efficacy for peritoneal metastasis compared to preoperative ctDNA, with AUC values of 0.93 and 0.86. Combined ctDNA/CTC positivity identified the highest recurrence risk (preoperative HR: 8.07, 95% CI 0.96-67.51, p = 0.0012; postoperative HR: 18.14, 95% CI 3.27-100.70, p = 0.0002).

CONCLUSIONS

The combination of postoperative ctDNA and CTC in PLF offered the highest accuracy (85%) and risk stratification in predicting peritoneal metastasis (30.30% vs. 66.67%, p = 0.0063). This method may guide the postoperative prophylactic intraperitoneal chemotherapy.