Prognostic stratification in gastric cancer with peritoneal metastasis: tumor biology and diagnostic modality as a surrogate for disease burden

Gastric adenocarcinoma with peritoneal metastasis (PM) has a poor prognosis, yet clinical outcomes vary significantly. This study aimed to identify independent prognostic determinants of PM-specific survival (PM-OS), focusing on tumor biology and disease burden surrogate. We retrospectively analyzed 166 patients with gastric adenocarcinoma and PM treated at a single center between 2015 and 2024. Prognostic factors were evaluated using multivariable Cox proportional hazards models. To mitigate immortal time bias and confounding by indication, receipt of systemic therapy was excluded from the primary multivariable model. The median PM-OS was 8.2 months (95% CI, 6.63–9.79). Patients diagnosed via surgical exploration (radiologically occult) achieved a significantly longer median PM-OS compared to those diagnosed radiologically (13.6 vs. 7.4 months; p = 0.003). In multivariable analysis, HER2 positivity (HR0.312, 95% CI 0.164–0.593; p < 0.001) and surgical diagnosis (HR 0.555, 95% CI 0.338–0.913; p = 0.020), interpreted as a surrogate for radiologically occult/low tumor burden, were identified as independent predictors of improved survival. Additionally, an optimized CA 19 − 9 cutoff (> 175.4 U/mL), unlike the standard threshold, significantly stratified survival. Traditional factors, including signet-ring cell histology and age, did not retain independent significance.In sensitivity analysis including systemic therapy, treatment was strongly associated with survival and the prognostic significance of HER2 and diagnostic context remained. Survival in gastric PM is fundamentally driven by HER2 status and the extent of PM. Surgical detection identifies a subgroup with limited, occult disease who achieve superior outcomes compared to those with radiologically overt metastases. Furthermore, the magnitude of biomarker elevation, rather than mere positivity, serves as a critical stratifier. These findings support a paradigm shift towards burden-based risk stratification to guide treatment intensity and clinical trial eligibility.