Peritoneal lavage fluid minimal residual cancer cells detection for early prediction of peritoneal metastasis in gastric cancer: A multi‐cohort validation study

Abstract Peritoneal metastasis (PM) remains a major cause of mortality in gastric cancer, yet current diagnostic methods lack sensitivity for early detection. This study aimed to validate the clinical value of minimal residual cancer cells detection in peritoneal lavage fluid (PLF) for predicting and monitoring PM. This study extended follow‐up analysis of a previously reported exploratory cohort ( n = 104) and validated findings in a new validation cohort ( n = 76). Using personalized mutation profiling, we detected cancer cell fraction (CCF) in pre‐resection PLF, post‐resection PLF, and circulating tumor DNA (ctDNA) in matched blood samples. Additionally, we monitored CCF and ctDNA dynamics in five patients receiving intraperitoneal chemotherapy (IPC). In the combined cohort ( n = 180), pre‐resection PLF CCF status showed 98% sensitivity and 80% specificity for PM prediction, while post‐resection PLF demonstrated 82% sensitivity and 90% specificity. Combining pre‐ and post‐resection PLF analysis achieved 100% sensitivity with 80% specificity. Compared to PLF cytology and plasma ctDNA, PLF CCF status emerged as the strongest independent predictor of PM (HR = 177.78, 95% CI: 23.14–22,968.19, p <.0001). In IPC‐treated patients, PLF CCF correlated with peritoneal tumor burden reduction and survival outcomes, highlighting its potential for monitoring therapeutic response. This study establishes PLF CCF detection as a robust and clinically valuable method for early prediction of PM and risk stratification in gastric cancer. In addition, PLF CCF monitoring holds potential for identifying patients who may benefit from prophylactic IPC before clear evidence of PM emerges, as well as for evaluating the efficacy of IPC treatment.