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

N/ANot Yet RecruitingNCT07625735

Shanghai Zhongshan Hospital3,000 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

3,000

Conditions

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 95 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Lymph Node Metastasis Rate Among LI-Positive Gastric Cancer Patients

LI positivity is defined as lymphatic invasion explicitly documented in the pathological report or tumor emboli within lymphatic vessels confirmed by D2-40 immunohistochemistry. LNM is defined as regional lymph node metastasis confirmed by postoperative pathological examination. The LNM rate among LI-positive patients is calculated as the number of patients with LNM divided by the total number of LI-positive patients in the corresponding group.

Time frame: At postoperative pathological assessment, approximately 14 days after upfront surgery

Secondary Outcomes

LI Positivity Rate According to MMR Status

This outcome evaluates differences in LI positivity rate between patients with dMMR and pMMR gastric cancer. LI positivity rate is calculated as the number of LI-positive patients divided by the total number of patients in each MMR group.

Time frame: At postoperative pathological assessment, approximately 14 days after upfront surgery

Overall LNM Rate According to MMR Status

This outcome evaluates differences in overall LNM rate between patients with dMMR and pMMR gastric cancer. Overall LNM rate is calculated as the number of patients with pathologically confirmed LNM divided by the total number of patients in each MMR group.

Time frame: At postoperative pathological assessment, approximately 14 days after upfront surgery

eCURA Risk Stratification and LI Contribution in the Gastric Cancer ESD Cohort

This outcome evaluates differences in eCURA classification, eCURA risk score distribution, and the contribution of LI to the risk score between dMMR and pMMR patients in the gastric cancer ESD cohort. LI contribution is assessed based on its role in eCURA-C2 classification and/or its component score contribution within the eCURA risk scoring system.

Time frame: At pathological assessment of the ESD specimen, approximately 14 days after ESD

LNM Rate Among LI-Positive Patients in the cohort undergoing additional gastrectomy after ESD

This outcome evaluates differences in LNM risk between LI-positive dMMR and pMMR patients with early gastric cancer who underwent additional surgery after ESD. LNM is defined as regional lymph node metastasis confirmed by pathological examination of the additional surgical specimen. LNM rate is calculated as the number of patients with LNM divided by the total number of LI-positive patients in each MMR group.

Time frame: At postoperative pathological assessment, approximately 14 days after additional surgery

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

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts