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Preoperative Predictors of Surgical Complexity After Neoadjuvant Immunochemotherapy in Non-small-cell Lung Cancer
Shinya Tane1, Kotaro Nomura2, Takuya Watanabe3
1Division of Thoracic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. shinyatane@gmail.com.
Background:
While neoadjuvant immunochemotherapy has improved outcomes of resectable nonsmall cell lung cancer (NSCLC), treatment-induced tissue changes can increase surgical complexity. This study aimed to identify preoperative predictors of technically challenging surgery following neoadjuvant immunochemotherapy.
Patients And Methods:
This multicenter retrospective analysis included 114 patients who underwent surgery after neoadjuvant nivolumab plus platinum-based chemotherapy at 29 institutions between March 2023 and July 2024. Challenging surgery was defined as one requiring bronchoplasty, pulmonary artery angioplasty, or pneumonectomy. Logistic regression was used to identify preoperative predictors for surgical complexity.
Results:
Twenty-one patients (18.4%) required challenging surgeries, including bronchoplasty (n = 13), pulmonary artery angioplasty (n = 1), double-sleeve resection (n = 4), and pneumonectomy (n = 3). These cases had longer operative times (340 ± 118 vs. 267 ± 98 min, p < 0.001) and more frequently required open thoracotomy (90.5% vs. 44.1%, p < 0.001). Conventional predictive factors (T/N status, programmed cell death ligand expression, radiological response, and treatment-to-surgery interval) showed no association with surgical complexity. Post-treatment extranodal extension (ENE) after neoadjuvant therapy and before surgery was the strongest predictor of challenging surgery (univariable odds ratio [OR] 7.06, 95% confidence interval [CI]: 1.45-34.41, p = 0.009). Post-treatment ENE demonstrated a higher predictive accuracy for challenging surgery (positive predictive value [PPV] 50.0%) than that of pathological ENE metastasis (PPV 14.3%); thus, positivity reflects treatment-induced anatomical changes rather than residual tumor invasion.
Conclusions:
Unlike conventional predictors, post-treatment ENE may predict surgical complexity after neoadjuvant immunochemotherapy. ENE may be a potential marker of treatment-induced anatomical complexity rather than residual tumor burden, enabling evidence-based surgical planning in the immunotherapy era.