Primary-tumor pathological response and postoperative residual nodal burden for risk stratification after neoadjuvant immunochemotherapy in gastric cancer

Primary-tumor regression and residual nodal disease may provide complementary prognostic information after neoadjuvant immunochemotherapy for locally advanced gastric cancer. This study evaluated whether integrating primary-tumor pathological response with the absolute residual positive lymph-node count improves postoperative risk stratification. This retrospective cohort study included 286 patients with locally advanced gastric or Siewert type III gastroesophageal junction adenocarcinoma who underwent neoadjuvant immunochemotherapy followed by curative-intent gastrectomy between 2018 and 2024. Patients treated at Henan Cancer Hospital formed the development cohort ( n = 210), and those treated at Taikang People’s Hospital formed a geographic validation cohort ( n = 76). Primary-tumor response was classified as major pathological response or non-major response. Residual nodal burden was modeled as log₂(positive-node count + 1). Multivariable Cox models assessed associations with disease-free and overall survival. Nested models based on pathological T and N categories were compared after adding primary-tumor response, continuous nodal burden, or both. Internal validation used 1,000 bootstrap resamples, and model coefficients were locked for geographic validation. During a median follow-up of 36.8 months, 92 disease-free survival events and 59 deaths occurred. Each doubling of the positive-node count plus one was independently associated with worse disease-free survival in the development cohort (adjusted hazard ratio, 1.58; 95% confidence interval, 1.34–1.86) and validation cohort (1.49; 1.14–1.95), with similar associations for overall survival (1.66; 1.35–2.04 and 1.57; 1.12–2.20, respectively). Three-year disease-free survival ranged from 90.4% among patients with major pathological response and no residual nodal disease to 51.6% among those with neither response. In geographic validation, adding continuous nodal burden increased the disease-free survival C-index by 0.034 (95% confidence interval, 0.006–0.063) beyond pathological T and N categories and by 0.030 (0.004–0.057) beyond these categories plus primary-tumor response. The full model achieved a validation C-index of 0.721. Residual positive lymph-node count was independently associated with survival after neoadjuvant immunochemotherapy. Combining continuous nodal burden with primary-tumor pathological response provided more informative postoperative risk stratification than conventional pathological staging alone. This framework may support individualized postoperative risk assessment, although prospective validation is required before clinical implementation.