Circulating tumour DNA in oligometastatic oesophago-gastric cancers: applications, challenges, and future directions

Oesophago-gastric cancer (OGC) is associated with a poor prognosis, with most patients presenting with or ultimately developing metastatic disease. Oligometastatic disease (OMD) represents an intermediate disease state characterised by a limited metastatic burden and, in selected patients, a more indolent clinical course. Increasing evidence suggests that carefully selected patients with OMD may benefit from local metastasis-directed therapies combined with systemic treatment. The OligoMetastatic Esophagogastric Cancer (OMEC) consortium has recently proposed a standardised consensus definition of OMD in OGC. However, this definition is primarily imaging-based, and conventional imaging may lack sensitivity for occult systemic disease and does not fully capture underlying tumour biology. Circulating tumour DNA (ctDNA) is a promising biomarker in OGC, with demonstrated value across locally advanced and metastatic settings. In the oligometastatic setting, ctDNA may provide a biological complement to imaging-based classification, enabling detection of molecular residual or occult systemic disease, improved prognostic stratification, and identification of patients most likely to benefit from local therapy. In this review, we summarise current evidence for the management of OMD in OGC and the evolving role of ctDNA in this disease. We discuss how ctDNA could refine prognostic stratification, therapeutic decision-making, and response assessment in oligometastatic OGC. Finally, we highlight key biological and methodological challenges and outline future directions, including the integration of ctDNA into OMD trial design to improve patient selection and response assessment.