Prognostic Value of Tumor Regression Systems and Lymph Node Regression in Gastric Adenocarcinoma After Neoadjuvant Chemotherapy.

[AIM] This study aimed to assess the prognostic significance of various histologic tumor regression grade (TRG) systems (Becker, American Joint Committee on Cancer (AJCC)/College of American Pathologists (CAP), Japanese Gastric Cancer Association (JGCA), JGCA2017, China, Mandard) and lymph node (LN) regression in patients with locally advanced gastric adenocarcinoma who underwent gastrectomy following neoadjuvant chemotherapy (NACT).

[METHODS] A retrospective cohort of 134 patients with locally advanced gastric adenocarcinoma from January 2020 to March 2024 who received NACT followed by gastrectomy was analyzed. Due to incomplete records, only the fact that patients received NACT was used, without specific regimen details. Surgical specimens were evaluated by two pathologists according to Becker, AJCC/CAP, JGCA, JGCA2017, China, and Mandard TRG systems. LN regression was categorized as positive/negative and coded as three categories (Code 1: metastasis without regression; Code 2: metastasis with regression; Code 3: regression without metastasis). Clinicopathologic variables, overall survival (OS) and disease-free survival (DFS) were analyzed by Kaplan-Meier curves and log-rank tests. Univariable and multivariable Cox regression models included each TRG subgroup as dummy variables and relevant covariates. Statistical significance was defined as < 0.05.

[RESULTS] The median follow-up time was 24 months (range 6-60). The median OS was 18.7 months (95% CI 16.2-21.3), while the median DFS was 16.4 months (95% CI 14.1-18.7). In the univariable analysis, JGCA2017 Score 0 (hazard ratio [HR] 0.28; 95% CI 0.12-0.65; = 0.003), Score 1a (HR 0.36; 95% CI 0.16-0.83; = 0.017), and clinical N3 stage (HR 1.95; 95% CI 1.15-3.30; = 0.013) were significantly associated with both OS and DFS. In multivariable Cox models, independent predictors of OS were JGCA2017 Score 0 (HR 0.25; 95% CI 0.11-0.59; = 0.002), Score 1a (HR 0.33; 95% CI 0.15-0.76; = 0.009), cN3 (vs cN1-2; HR 2.05; 95% CI 1.18-3.56; = 0.010), and positive LN regression (HR 0.42; 95% CI 0.23-0.77; = 0.005). Regarding DFS, JGCA2017 Score 0 (HR 0.30; 95% CI 0.12-0.75; = 0.009), cN3 (vs cN1-2; HR 1.90; 95% CI 1.10-3.30; = 0.020), and positive LN regression (HR 0.50; 95% CI 0.28-0.90; = 0.018) were independent predictors. Other TRG systems' subgroups did not remain significant in multivariable models. Notably, the JGCA2017 Score 0/1a categories independently predicted better OS and DFS, whereas positive LN regression also emerged as a protective prognostic factor.

[CONCLUSIONS] JGCA2017 subgroups are the most robust prognostic indicators for OS and DFS in patients with gastric adenocarcinoma following NACT. Positive LN regression is also an independent protective factor. Prospective validation and international standardization of these grading systems are warranted.