PD07.06. Lymphovascular and Perineural Invasion Identifies High-Risk Disease and Candidates for Postoperative Therapy After Neoadjuvant Immunochemotherapy in Esophageal Squamous Cell Carcinoma

Abstract

Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Despite increasing use of neoadjuvant chemoimmunotherapy (nCIT) for locally advanced esophageal squamous cell carcinoma (ESCC), postoperative risk stratification remains suboptimal. Lymphovascular invasion (LVI) and perineural invasion (PNI) represent markers of aggressive tumor biology, yet their combined prognostic value and implications for adjuvant treatment in the nCIT setting have not been fully clarified. This study investigated the survival impact of concurrent LVI/PNI (defined as LNI) and explored its role in guiding postoperative therapeutic decisions. We retrospectively evaluated 473 patients with ESCC who underwent nCIT followed by curative-intent resection. LVI and PNI were assessed on surgical specimens, and patients were categorized according to LNI status. Overall survival (OS), disease-free survival (DFS), and recurrence patterns were compared using propensity score matching and multivariable Cox regression to adjust for residual confounders. An independent external dataset was used for validation of prognostic associations and treatment interactions. LNI was identified in 21% of resected specimens. Patients with LNI exhibited significantly lower 3-year OS (49.8% vs 76.4%) and DFS (41.7% vs 69.3%) compared with LNI-negative counterparts, differences that persisted after matching and multivariable adjustment. LNI independently predicted worse OS (HR 1.52; P = 0.022) and DFS (HR 1.40; P = 0.045). Recurrence was more frequent among LNI-positive patients (39.4% vs 19.8%), with a predominance of locoregional failure. Importantly, in the LNI-positive subgroup, receipt of adjuvant therapy was associated with substantial improvement in 3-year OS (56.8% vs 32.4%) and DFS (49.7% vs 20.7%), corresponding to a significant reduction in mortality risk (adjusted HR 0.43; P = 0.002). External validation confirmed both the independent adverse prognostic impact of LNI and the survival benefit conferred by adjuvant therapy in this high-risk population. The coexistence of lymphovascular and perineural invasion after nCIT delineates a biologically aggressive ESCC phenotype with high recurrence risk and inferior survival. However, these patients appear to derive meaningful benefit from postoperative adjuvant therapy. Incorporation of LNI status into postoperative risk assessment may facilitate precision-guided adjuvant treatment strategies in the contemporary immunochemotherapy era.