2142 - Prognostic Value of Tumor Microenvironment Biomarkers and Tumor Regression Grading in Esophageal Squamous Cell Carcinoma Patients with Non-Pathological Complete Response (Non-pCR)

Purpose/Objective(s):

To evaluate the prognostic value of tumor microenvironment (TME) indicators and tumor regression grade (TRG) in locally advanced esophageal squamous cell carcinoma (ESCC) patients with non-pathological complete response (non-pCR) after neoadjuvant therapy, and to identify potential biomarkers for guiding adjuvant treatment decisions.

Materials/Methods:

A retrospective analysis of 120 non-pCR ESCC patients (2018–2021) was conducted. Hematoxylin-eosin (H&E) and immunohistochemical (IHC) staining were performed on surgical specimens to assess tertiary lymphoid structures (TLSs), programmed death-ligand 1 (PD-L1) expression, tumor-infiltrating lymphocytes (TILs), and TRG. The correlations of these factors with survival outcomes were analyzed.

Results:

Primary tumor TRG was classified as grade 1, 2, and 3 in 5, 33, and 82 patients, respectively. With a median follow-up of 53 months, the 5-year DFS and OS rates were 50.3% and 56.6%, respectively.

1. TME Characteristics: Mature TLSs (mTLSs) were present in 68.3% (82/120) of patients and were associated with an earlier ypT stage (P=0.006).PD-L1 positivity correlated with poorer differentiation and advanced ypT stage (P<0.05). A higher density of CD8+ TILs was associated with more advanced ypT stage (P=0.019).
2. Prognostic Factors:Survival analysis revealed that patients with mTLSs had significantly longer DFS and OS than those without (both P<0.05). Multivariate Cox regression analysis confirmed mTLSs as an strong independent protective factor for OS (HR=0.40, P=0.002), while perineural invasion, ypN+, and PD-L1 positivity were independent risk factors (P<0.05). No significant association was found between primary tumor TRG and patient prognosis.
3. Predictive Value for Adjuvant Therapy: Adjuvant therapy did not improve survival overall. In subgroup analysis, patients with low CD8+ TIL density had worse DFS/OS with adjuvant therapy (P<0.05). In contrast, patients with high CD8+ TILs density derived an OS benefit (P=0.039). mTLSs or PD-L1 status alone did not predict adjuvant therapy benefit.

Conclusion:

The TME after neoadjuvant therapy is a critical prognostic determinant in non-pCR ESCC. mTLSs signify favorable survival, while PD-L1 positivity indicates poor prognosis. CD8+ TIL density shows promise as a predictive biomarker for adjuvant therapy efficacy, potentially guiding more individualized post-operative treatment strategies.