A real-world multicenter study on postoperative adjuvant treatment patterns and prognostic implications following neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma
TL;DR
For ESCC patients receiving nICT, postoperative adjuvant treatment can provide survival benefits, particularly more pronounced in non-pCR patients and those with advanced postoperative pathological stages, particularly more pronounced in non-pCR patients and those with advanced postoperative pathological stages.
Abstract
Background With the widespread application of neoadjuvant immunochemotherapy (nICT) in locally advanced resectable esophageal squamous cell carcinoma (ESCC), determining the optimal postoperative adjuvant treatment strategy has become a critical clinical issue. This study aimed to evaluate the efficacy of different adjuvant treatment patterns and identify beneficial populations. Methods This was a multicenter real-world study involving 612 ESCC patients from six national centers who underwent R0 resection after nICT. Patients were divided into three groups based on postoperative treatment patterns: Clinical Observation (CO group, n=337), Postoperative Adjuvant Chemotherapy (POCT group, n=80), and Postoperative Adjuvant Chemoimmunotherapy (POICT group, n=195). Study endpoints included overall survival (OS), disease-free survival (DFS), and recurrence patterns. Results Multivariate analysis of the whole cohort showed that both POCT and POICT reduced the risk of death (HR = 0.51, P = 0.007; HR = 0.49, P<0.001) and disease progression (HR = 0.48, P = 0.003; HR = 0.48, P<0.001) compared with CO. Subgroup analysis indicated that among patients without pathological complete response (non-pCR), both POCT and POICT significantly improved OS and DFS (P<0.05), with no statistical difference between the two groups. In pCR patients, only POICT showed an OS benefit (P = 0.014). Patients with postoperative pathological stage III benefited in both OS and DFS (P<0.05) from POCT and POICT. After propensity score matching (PSM), the 3-year OS (74.7% vs 79.8%) and DFS (63.1% vs 67.2%) rates between the POCT and POICT groups showed no significant difference (P>0.05). Postoperative adjuvant therapy was an independent factor affecting OS in patients with more advanced yT, yN, and yTNM stages, and an independent prognostic factor for DFS in patients with yN2 stage and advanced yTNM stages. Failure pattern analysis revealed no statistically significant differences in the cumulative incidence of locoregional recurrence or distant metastasis between the POCT and POICT groups (χ²=0.279, 2.828; P = 0.597, 0.093). Conclusion For ESCC patients receiving nICT, postoperative adjuvant treatment can provide survival benefits, particularly more pronounced in non-pCR patients and those with advanced postoperative pathological stages. Adding immunotherapy to chemotherapy did not significantly further improve survival outcomes in the overall PSM-matched population; however, in pCR patients, POICT showed OS benefit while POCT did not, suggesting potential differential efficacy according to pathological response.