Effects of surgery on cancer metastasis: biological mechanisms and perioperative implications

Abstract

Cancer metastasis remains the leading cause of cancer-related mortality, and the perioperative period has emerged as a critical window during which metastatic progression may be influenced. While surgical resection remains central to curative cancer treatment, accumulating preclinical, translational, and clinical evidence suggests that surgery-associated tissue injury, inflammation, neuroendocrine stress responses, immune perturbation, and host physiological factors can modulate metastatic dynamics in context-dependent ways. This review integrates experimental and clinical literature to examine the biological mechanisms through which surgery may influence metastatic progression, with emphasis on perioperative inflammatory responses, immune suppression, circulating tumor cells (CTCs), epithelial-mesenchymal transition (EMT), tumor dormancy, neutrophil extracellular traps (NETs), circulating tumor cell clusters, and emerging interactions involving the gut microbiome and tumor microenvironment. We additionally examine how perioperative physiological status, prehabilitation, and multidisciplinary optimization strategies may influence perioperative resilience and postoperative recovery. We further discuss emerging approaches aimed at mitigating surgery-associated metastatic vulnerability, including perioperative systemic therapies, immunomodulation, neoadjuvant and perioperative immunotherapy, minimally invasive surgical approaches, and tumor microenvironment targeted interventions. A clearer understanding of perioperative biological perturbations may inform the development of integrated perioperative oncology strategies to reduce metastatic risk and improve long-term oncologic outcomes.