The Role of HIPEC in Isolated Cytology-Positive Gastric Cancer: Nodal Metastasis Dominates Prognosis, HIPEC Remains Unproven

Background The therapeutic role of hyperthermic intraperitoneal chemotherapy (HIPEC) in isolated cytology-positive (Cy + ) gastric cancer without peritoneal metastases (Peritoneal Cancer Index score 0) remains investigational. This study evaluated survival outcomes, prognostic factors, and exploratory HIPEC efficacy in Cy + patients treated with modern multimodal therapy. Methods We retrospectively analyzed 558 patients with gastric adenocarcinoma who received neoadjuvant chemotherapy followed by radical gastrectomy (2017–2023). Propensity score matching (1:5) balanced 47 Cy + and 511 cytology-negative (Cy − ) patients for pathologic stage, treatment response, and adjuvant completion. Inverse probability of treatment weighting validated matched results. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Results Cy + patients had inferior outcomes (median OS 24.7 vs. 57.2 months; hazard ratio [HR] 2.09; p <0.001; DFS 14.7 vs. 41.4 months; HR 1.62; p =0.012), which persisted after matching and inverse probability of treatment weighting. Within the Cy + cohort, nodal metastasis was the strongest prognostic factor, tripling recurrence risk (DFS HR 3.06; p =0.018). Among 23 Cy + patients undergoing HIPEC, 2-year DFS was 41.4 versus 29.5% ( p =0.398) and OS was 55.6 versus 42.4% ( p =0.903) compared with non-HIPEC cases. HIPEC increased operative time and hospital stay but showed comparable morbidity and no 90-day mortality. Conclusion Cytology positivity independently predicted poor survival after curative gastrectomy, but nodal status was the dominant prognostic determinant. HIPEC was well tolerated but conferred no significant survival advantage, underscoring its investigational role pending prospective validation.