Multicenter Study of Clinical-Pathological Correlation in cT2N0 Gastric Cancer and Its Prognostic Implications

Gastric cancer remains one of the leading causes of cancer-related mortality worldwide, ranking fifth in incidence and fourth as a cause of cancer-related death, according to the latest data from the World Health Organization (WHO). Currently, treatment selection for resectable disease is based on the clinical TNM classification according to the 8th edition of the American Joint Committee on Cancer (AJCC), which allows for differentiation between early-stage tumors eligible for resection as the first (primary) treatment and locally advanced disease, in which perioperative treatment has been shown to improve survival.

However, there is a subgroup of patients for whom this approach has significant limitations: those diagnosed with cT2N0 gastric cancer.

The cT2N0 stage represents a transition point between early-stage and locally advanced disease, where the indication for primary surgery or perioperative treatment is controversial. Population-based studies have shown that the concordance between clinical and pathological staging in gastric cancer is suboptimal, with error rates approaching 40%.

This phenomenon is particularly pronounced in the cT2N0 subgroup, where agreement can drop as low as 34.7%, making it the group with the poorest diagnostic accuracy.

In this context, endoscopic ultrasound (EUS) has traditionally been considered the most accurate tool for preoperative locoregional staging of gastric cancer, especially in the assessment of tumor depth (T). EUS allows for detailed visualization of the different layers of the gastric wall, making it the gold standard for assessing tumor invasion. However, current evidence shows more heterogeneous results than previously assumed, with an overall accuracy for T staging of approximately 64.2% .

Importantly, the accuracy of EUS is particularly limited in intermediate stages such as T2, where discrimination between invasion of the muscularis propria and the subserosa can be technically complex, and where published rates of understaging (≈22.9%) and overstaging (≈12.9%) have been reported [7].

Furthermore, in addition to the limitation in diagnostic accuracy for "T" staging, the understaging rate is elevated due to the presence of undetected lymph node in the preoperative diagnosis. The sensitivity of imaging techniques for lymph node detection falls within suboptimal ranges (≈45-60%), with occult lymph node involvement accounting for more than 70% of cases of understaging.

Consequently, approximately half of the patients classified as cT2N0 are ultimately restaged to more advanced stages following surgical resection.

Paradoxically, the available evidence also suggests that not all patients with cT2N0 benefit from more intensive strategies. In a multicenter European cohort, neoadjuvant chemotherapy was not associated with improved survival compared with primary surgery. Furthermore, the benefit of postoperative treatment depends on the initial clinical stage. However, the ESMO guidelines for the treatment of gastric cancer propose neoadjuvant therapy for cT2N0 disease in their management algorithm. Tumor downstaging following neoadjuvant therapy is associated with improved survival, although the ability to select appropriate candidates preoperatively remains limited.

Finally, regarding the management of this cT2N0 group, the available scientific evidence comes primarily from U.S. and Asian cohorts, with limited European studies. No European esophagogastric cancer population registry has provided evidence in this field.

Consequently, cT2N0 gastric cancer represents a critical knowledge gap.

Inclusion criteria

• gastric adenocarcinoma, cT2N0 classification (CT scan/echoendoscopy), surgery with or without neoadjuvant therapy, pTNM stage recorded.

Exclusion criteria

• metastatic disease, non-curative resections.