The peritoneum is a common site for metastasis in gastroesophageal cancers (GOC). Peritoneal metastasis leads to upstaging, altering the treatment pathway. Currently, peritoneal lavage cytology (PLC) is the gold standard for detection of peritoneal micro-metastasis. However, PLC has variable sensitivity in GOC, detecting 10% - 80% of micro-metastases. This study aimed to develop and compare a tumour-informed platform for detection of peritoneal tumour DNA (ptDNA) against PLC in peritoneal lavage fluid from patients with GOC. Peritoneal lavage fluid was collected intraoperatively from 42 GOC patients. PLC and clinically detectible peritoneal metastases were confirmed by histopathology. Whole-genome sequencing of tumour tissue and buffy coat was performed to identify somatic variants for individual patients, with subsequent tracking of up to 96 personalised variants in the peritoneal lavage fluid. Positive ptDNA was found in 13 out of 33 PLC negative cases. ptDNA was detectable in 100% of cases with macroscopic peritoneal disease that were PLC positive. In two cases of PLC positivity with no macroscopic peritoneal disease, ptDNA was also detected. Notably, in 2 patients that had macroscopic peritoneal disease and were PLC negative, ptDNA was detected, suggesting a higher sensitivity of ptDNA compared to PLC. This pilot study demonstrated the feasibility of a tumour-informed ptDNA detection platform with increased sensitivity compared to PLC in GOC. To further validate the clinical utility of ptDNA we are proceeding to a larger multi-centre prospective cohort study.