PATTERNS OF DEVELOPMENT OF PATHOMORPHOLOGICALTUMOR REGRESS AFTER NEOADJUVANT CHEMOTHERAPYFOR GASTRIC CANCER: EXPERIENCE OF THE NATIONALRESEARCH ONCOLOGY CENTER

Abstract

Background: Gastric cancer remains one of the leading causes of cancer-related mortality worldwide. Perioperative
neoadjuvant polychemotherapy (NAPCT) using the FLOT regimen has improved long-term outcomes; however, the prognostic
value of pathological tumor regression grade (TRG) and its association with clinicopathological factors is not yet fully elucidated.
Objective: To evaluate the association between tumor regression grade (TRG) assessed by the Mandard system,
clinicopathological characteristics, and overall (OS) and relapse-free survival (RFS) in patients with locally advanced gastric
cancer treated with NAPCT using the FLOT regimen.
Materials and methods: A single-center retrospective cohort study was conducted, including 74 patients with stage II–III
gastric adenocarcinoma treated with perioperative FLOT chemotherapy followed by surgery between 2020 and 2024. TRG was
evaluated using the Mandard classification. Correlations were calculated using Spearman’s coefficient. Survival was analyzed by
Kaplan–Meier method with log-rank test and univariate Cox regression. Statistical significance was set at p<0.05.
Results: TRG was assessed in 70 resection specimens: TRG1 — 9 (12.9%), TRG2 — 2 (2.9%), TRG3 — 23 (32.9%), TRG4
— 10 (14.3%), TRG5 — 26 (37.1%). A clinically significant response (TRG1–2) was observed in 16% of patients. TRG showed
significant correlation with ypT (ρ=0.51; p<0.001), ypN (ρ=0.36; p=0.0037), and the number of metastatic lymph nodes (ρ=0.36;
p=0.0025). The presence of signet ring cells was associated with higher tumor grade (ρ=0.308; p=0.008) and ypT (ρ=0.324;
p=0.007), but not with TRG. In univariate analysis, OS was significantly associated with ypN (ρ=–0.24; p=0.048) and the number of
metastatic lymph nodes (ρ=–0.28; p=0.021). Median OS and RFS were not reached. Kaplan–Meier analysis demonstrated
significantly better OS and RFS in responders (TRG1–2) compared to non-responders (log-rank χ²=7.9; p=0.005 and χ²=10.86;
p=0.001, respectively).
Conclusions: A strong pathological response after FLOT-based NAPCT is associated with improved survival; however,
residual lymph node metastasis (ypN and number of involved nodes) remains the dominant prognostic factor. TRG should be
interpreted in the context of nodal status. Further prospective multicenter studies with standardized pathological assessment
are warranted to validate the independent prognostic role of TRG.