From local eradication to immune priming: Paradigm shift of hyperthermic intraperitoneal chemotherapy in gastric cancer therapy

Table 1 Summary of key evidence on hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer

Ref.	Population and design	DFS outcome	OS outcome	Key findings and interpretation
Pivotal recent evidence
Lian et al[9], 2026	The pT4 stage, non-metastatic. Retrospective cohort study	Significantly improved (higher 3-year DFS rate)	Favorable trend (not significant)	Provides key evidence that postoperative HIPEC reduces peritoneal recurrence and improves DFS, forming the basis for re-evaluating its role as an immune primer
Supportive evidence: Retrospective studies
Reutovich et al[10], 2019	Serosa-invasive (pT4), non-metastatic. Retrospective study	Significantly improved	Improved	Demonstrates that HIPEC reduces peritoneal recurrence and improves survival in a high-risk cohort, supporting precision application
Liu et al[6], 2023	Locally advanced GC. Propensity score-matched analysis	Significantly improved (HR = 0.592; P = 0.042)	Trend toward improvement	Confirms that prophylactic HIPEC reduces peritoneal recurrence risk and improves DFS in clinical T4 patients
Supportive evidence: Meta-analysis
Granieri et al[4], 2021	GC (mixed stages). Meta-analysis of RCTs	Significant benefit	Potential benefit/requires confirmation	Pooled data supports a consistent DFS advantage. OS benefit appears contingent on patient selection (e.g., high-risk features)
Evidence illustrating the “central paradox”
Fan et al[7], 2021	Locally advanced GC (M0). Phase II RCT	Improved (primary endpoint met)	No significant difference	Epitomizes the central paradox: A clear, protocol-defined DFS benefit did not translate into an OS advantage, highlighting complexities in endpoint interpretation and subsequent therapies
Gong et al[17], 2024	Locally advanced GC. Retrospective (propensity score matching) study	Significantly improved (HR = 0.569; P = 0.013)	No significant difference	Reinforces the paradox pattern: Significant reduction in isolated peritoneal metastasis and DFS improvement, yet no OS benefit, underscoring the need for combination strategies (e.g., with immunotherapy)

It synthesizes the primary clinical evidence regarding hyperthermic intraperitoneal chemotherapy for locally advanced gastric cancer, highlighting the consistent pattern of improved disease-free survival and reduced peritoneal recurrence, particularly in high-risk populations (e.g., pathological T4 stage). The contrasting overall survival outcomes between supportive retrospective studies and randomized trials epitomize the “central paradox” in the field, which forms the rationale for re-evaluating hyperthermic intraperitoneal chemotherapy’s mechanism beyond local cytotoxicity and toward systemic immune modulation. DFS: Disease-free survival; GC: Gastric cancer; HIPEC: Hyperthermic intraperitoneal chemotherapy; HR: Hazard ratio; OS: Overall survival; pT4: Pathological T4; RCT: Randomized controlled trial.