Perioperative local anesthetics as modulators of tumor progression and metastasis

Cancer surgery remains a cornerstone of treatment for solid malignancies; however, perioperative factors increasingly emerge as critical modulators of tumor recurrence and metastasis. Accumulating evidence suggests that anesthesia techniques and analgesic strategies can profoundly influence tumor biology, immune competence, and long-term oncologic outcomes. In particular, opioids-while indispensable for perioperative analgesia-have been associated with enhanced tumor progression through direct stimulation of oncogenic signaling pathways and suppression of antitumor immunity. In contrast, regional anesthesia and local anesthetics have gained attention for their opioid-sparing properties and potential antitumor effects. Beyond effective analgesia, local anesthetics exert multifaceted actions on tumor progression by inhibiting voltage-gated sodium channels, attenuating inflammatory signaling, suppressing EGFR-driven oncogenic pathways, restraining mesenchymal stem cell-mediated tumor support, and preserving or enhancing antitumor immune responses. This review summarizes current preclinical and clinical evidence elucidating the mechanisms by which local anesthetics and regional anesthesia modulate tumor growth, metastasis, and immune surveillance. Understanding these perioperative interactions provides a compelling rationale for integrating anesthetic strategies into comprehensive oncologic care aimed at improving long-term cancer outcomes.