Nodal burden modifies the prognostic significance of perineural invasion in stage I-III gastric cancer
In brief
Perineural invasion increases death risk 38% in low-node gastric cancer
In a study of 12,898 stage I-III gastric cancer patients, perineural invasion raised overall-survival hazard by about 38% in those with no or few positive nodes (N0-N1) but the effect faded in patients with extensive nodal disease (N2-N3). The finding was strongest in tumors prone to peritoneal spread, suggesting that PNI could guide more aggressive peritoneal surveillance in early-node patients.
- Journal
- Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Q1)
- Published
- 26 July 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Qi Wang, Hongxue Meng, Shizheng Xiong, Xiaoyan Zhang, Midie Xu
- PMID
- 42503154
- DOI
- 10.1007/s10120-026-01784-1
Why clinicians should know about it
- Picked for Gastroenterology (paper of the day, 27 July 2026): Prognostic factor analysis in gastric cancer surgery
- Picked for Pathology and Forensic Medicine (paper of the day, 27 July 2026).
Abstract
BACKGROUND: Perineural invasion (PNI) is an established adverse prognostic factor in gastric cancer, but whether its prognostic effect varies with nodal burden and first metastatic site remains unclear. METHODS: We retrospectively analyzed 12,898 patients with stage I-III gastric cancer who underwent curative-intent R0 gastrectomy at Fudan University Shanghai Cancer Center between 2000 and 2022. Multivariable Cox models with a pre-specified PNI-by-positive-node interaction estimated associations with overall survival (OS) and progression-free survival (PFS). First distant metastatic site was evaluated using Fine-Gray and Firth logistic site-contrast models. The PNI-nodal-burden association was assessed in an independent pathology cohort and the ACRG cohort. RESULTS: Each additional positive lymph node attenuated the PNI-associated hazard ratio for OS (interaction HR, 0.976) and PFS (interaction HR, 0.977; both interaction P < 0.001). PNI was independently associated with poorer OS (HR, 1.38; 95% CI 1.20-1.59) and PFS (HR, 1.32; 95% CI 1.15-1.51) in N0-N1 disease, but the associations were attenuated in N2-N3 disease (OS: HR, 1.12; 95% CI 1.00-1.24; PFS: HR, 1.09; 95% CI 0.99-1.21). Among N0-N1 patients with pT3-pT4 disease and liver-only or peritoneal-only first metastasis, PNI was associated with peritoneal rather than hepatic dissemination (OR, 3.87; 95% CI 1.54-10.63). CONCLUSIONS: The prognostic association of PNI was modified by nodal burden and was most evident in N0-N1 gastric cancer. These site-specific findings support prospective evaluation of PNI-informed, peritoneum-directed surveillance.
Abstract as published, via PubMed.
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