Time to define the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in T4 colon cancer

T4 colon adenocarcinoma, defined by tumour penetration of the visceral peritoneum or invasion of adjacent structures, carries a 15%-30% risk of peritoneal metastases (PM) despite curative resection and adjuvant systemic chemotherapy. Hyperthermic intraperitoneal chemotherapy (HIPEC) offers a biologically rational strategy to eradicate occult intraperitoneal tumour cells by exposing the peritoneal cavity to heated cytotoxic agents with enhanced penetration and synergistic thermal cytotoxicity. Although widely used with cytoreductive surgery for established PM, its prophylactic or adjuvant role in non-metastatic T4 disease remains uncertain. Randomized evidence is conflicting and divergent outcomes may be explained by a mechanistic triad encompassing: (1) timing of intraperitoneal drug exposure relative to early tumour implantation and adhesion formation; (2) pharmacological, thermal, and dosing characteristics of the HIPEC regimen, including its most often single administration; and (3) underlying biological heterogeneity within T4 tumours. Thus, HIPEC for T4 colon cancer remains promising in selected patients, and it may be established as routine if ongoing studies rigorously define timing, agent selection and biomarker-driven patient stratification.