MMR Status Modulates the Predictive Value of Lymphatic Invasion for Lymph Node Metastasis in Gastric Cancer

Fudan University

Status: Begins enrollment this month

Conditions: Mismatch Repair Deficient or MSI-High Solid Tumors; Gastric / Gastroesophageal Junction Adenocarcinoma; Lymph Node Metastasis; Lymphatic Invasion

Treatments: Other: Mismatch repair (MMR) status; Other: Lymphatic invasion status

Study type: Observational

Funder types: Other

Identifiers

NCT07625735

ZSGC

Details and patient eligibility

About

Brief Summary

Lymph node metastasis (LNM) is a key factor influencing treatment decisions and prognosis in patients with gastric cancer. Lymphatic invasion (LI) is an important pathological predictor of LNM and a core component of the eCURA risk scoring system after endoscopic submucosal dissection (ESD) for early gastric cancer. However, whether LI has the same predictive value for LNM across different mismatch repair (MMR) statuses remains unclear. Compared with proficient mismatch repair (pMMR) gastric cancer, deficient mismatch repair (dMMR) gastric cancer has distinct molecular pathological features and an immune-enriched tumor microenvironment. In early gastric cancer, if LI is associated with a lower LNM risk in dMMR tumors than in pMMR tumors, existing LI-based eCURA risk assessment may overestimate LNM risk in patients with dMMR early gastric cancer and consequently affect decisions regarding additional surgery after ESD. Therefore, this study aims to systematically evaluate the impact of MMR status on the association between LI and LNM using upfront-surgery and post-ESD additional-surgery cohorts from our center, and to explore the potential clinical value of MMR status in refining eCURA-based risk stratification for early gastric cancer.

Enrollment: 3,000 estimated patients

Sex: All

Ages: 18 to 95 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Upfront surgery cohort

   • Patients who underwent radical surgery for gastric cancer at Zhongshan Hospital, Fudan University.
   • Patients who did not receive neoadjuvant chemotherapy, radiotherapy, immunotherapy, or other antitumor treatments that may affect the pathological assessment of the primary tumor or lymph node metastasis before surgery.
   • Patients with pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma after surgery, including Siewert type II and III tumors only.
   • Patients with definite pathological assessment of lymphatic invasion and regional lymph node status.
   • Patients with available and definite MMR status.

2. ESD cohort

   • Patients who underwent ESD for gastric cancer at Zhongshan Hospital, Fudan University.
   • Patients with pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma after ESD, including Siewert type II and III tumors only.
   • Patients with complete post-ESD pathological information, including histological type, depth of invasion, tumor size, ulcerative findings, lymphatic invasion status, venous invasion status, horizontal margin status, and vertical margin status.
   • Patients with available and definite MMR status.

Exclusion criteria

1. Upfront surgery cohort

   • Patients with other pathological types, such as gastric squamous cell carcinoma or neuroendocrine carcinoma.
   • Patients who received neoadjuvant treatment before surgery, including chemotherapy, radiotherapy, immunotherapy, targeted therapy, or other systemic antitumor treatments.
   • Patients with missing postoperative pathological information, resulting in inability to determine lymphatic invasion or regional lymph node metastasis status.
   • Patients with missing or indeterminate MMR status.
   • Patients with concurrent malignancies that may interfere with the determination of the origin of lymph node metastasis.

2. ESD cohort

   • Patients with other pathological types, such as gastric squamous cell carcinoma or neuroendocrine carcinoma.
   • Patients with missing post-ESD pathological information that precludes eCURA classification, eCURA risk score calculation, or assessment of lymphatic invasion status.
   • Patients with missing or indeterminate MMR status.

Trial design

3,000 participants in 2 patient groups

dMMR gastric cancer

Description:

Patients with gastric cancer classified as deficient mismatch repair (dMMR) based on routine pathological testing.

Treatment:

Other: Lymphatic invasion status

Other: Mismatch repair (MMR) status

pMMR gastric cancer

Description:

Patients with gastric cancer classified as proficient mismatch repair (pMMR) based on routine pathological assessment.

Treatment:

Other: Lymphatic invasion status

Other: Mismatch repair (MMR) status