Regional Anesthesia and the Perioperative Inflammatory Window in Cancer Surgery: From Surgical Stress to Immunometabolic Reprogramming.

The impact of anesthetic technique on long-term oncologic outcomes remains controversial. While early observational data suggested that regional anesthesia might reduce cancer recurrence, large randomized trials have failed to demonstrate consistent survival benefits. This apparent contradiction may not reflect biological neutrality, but rather a mismatch between trial design and the inflammatory biology of the perioperative period. Surgical resection provokes an acute and intense inflammatory surge characterized by sympathetic activation, cytokine release, neutrophil extracellular trap formation, endothelial activation, and transient suppression of cellular immunity. During this perioperative inflammatory window, circulating tumor cells encounter a biologically permissive microenvironment that may facilitate immune evasion, adhesion, and early metastatic niche establishment. The magnitude of this inflammatory response varies across patients and may represent a critical, yet under-recognized, determinant of tumor-host dynamics. Anesthetic and analgesic strategies influence this inflammatory cascade. By attenuating nociceptive signaling and sympathetic activation, regional anesthesia may modulate perioperative immune and immunometabolic pathways. However, it should not be framed as an anti-cancer therapy per se, but rather as a potential regulator of the transient inflammatory milieu that shapes early oncologic biology. We propose that prior neutral trials may reflect methodological misalignment, including heterogeneous tumor populations, absence of inflammatory stratification, and reliance on distant survival endpoints without mechanistic correlates. Future investigations should integrate perioperative immune phenotyping, inflammatory biomarkers, and tumor subtype stratification to determine whether modulation of acute surgical inflammation meaningfully alters early tumor-host interactions. Reconceptualizing the perioperative period as a biologically active inflammatory interface may refine the anesthesiologist's role within perioperative oncology and open new avenues for precision-based perioperative modulation.