Prognostic impact of neoadjuvant therapy and nomogram development in early-stage and locally advanced Siewert type II adenocarcinoma of the esophagogastric junction based on the SEER database

Background: Despite the rising global incidence of adenocarcinoma of the esophagogastric junction (AEG), treatment for Siewert type II AEG remains controversial, particularly regarding whether neoadjuvant therapy confers differential benefit according to stage. Locally advanced patients may benefit from neoadjuvant therapy, yet the benefit of additional adjuvant therapy remains unclear. This study therefore aimed to evaluate the stage-specific efficacy of neoadjuvant therapy and to explore the value of adjuvant therapy following neoadjuvant treatment in locally advanced disease.

Methods: Patients diagnosed with Siewert type II AEG were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Survival differences among patients were assessed using the Kaplan–Meier method and log‑rank test. To minimize baseline imbalances, propensity score matching (PSM) was performed, and multivariable Cox regression analyses were conducted before and after PSM to adjust for potential confounders. Univariate and multivariate Cox regression analyses were employed to identify independent prognostic factors. A nomogram predicting overall survival (OS) was constructed based on the variables selected by Cox regression. The predictive performance of the nomogram was evaluated by the concordance index (C‑index), receiver operating characteristic (ROC) curves with area under the curve (AUC) values, calibration plots, and decision curve analysis (DCA).

Results: A total of 1,847 patients were enrolled. In the overall cohort, no significant OS difference was observed between surgery alone (SA) and neoadjuvant-based therapy combined with surgery (NS) groups after PSM (P=0.14). Stage‑stratified analysis showed that neoadjuvant therapy significantly improved OS in locally advanced patients (P<0.001), but not in early‑stage patients (P=0.06). Among locally advanced patients receiving neoadjuvant therapy, adding adjuvant therapy provided no additional OS benefit (P=0.87). Prognostic nomograms were constructed for early‑stage and locally advanced patients. For the early‑stage model, the C‑index was 0.696 in the training set and 0.669 in the testing set, with AUC values for 1‑, 3‑, and 5‑year OS of 0.653, 0.730, and 0.748 in the training set, and 0.698, 0.702, and 0.692 in the testing set. For the locally advanced model, the C‑index was 0.671 and 0.635 in the training and testing sets, respectively, with AUC values of 0.741, 0.723, and 0.725 in the training set, and 0.693, 0.684, and 0.690 in the testing set. Calibration and DCA confirmed satisfactory predictive performance and clinical utility for both models.

Conclusions: Neoadjuvant therapy, predominantly chemoradiotherapy, significantly improved OS in locally advanced Siewert type II AEG but not in early-stage disease. In locally advanced patients,adding adjuvant therapy after neoadjuvant therapy did not provide additional OS benefit. These findings suggest that treatment strategies may differ by stage, though this observation warrants further validation through prospective studies.