A multicenter prediction model for false-positive clinical nodal disease in < 4-cm NSCLC: clinical implications for upfront surgery versus neoadjuvant therapy

BACKGROUND: Perioperative immunochemotherapy is recommended for resectable non-small cell lung cancer (NSCLC) with ≥ 4-cm tumors or clinical nodal involvement (cN(+)). Therefore, accurate preoperative nodal assessment is crucial in < 4-cm tumors, where false-positive cN staging should be carefully considered. This multicenter study aimed to develop and validate a prediction model to identify patients at high risk of cN(+)pN(-) disease. METHODS: The development cohort included 251 patients with tumors < 4 cm who were diagnosed as cN(+) using positron emission tomography and underwent curative anatomical resection with mediastinal lymph node dissection between 2010 and 2020. The model predicting cN(+)pN(-) was developed and subsequently validated in a temporally independent validation cohort of 108 patients treated during periods different from those of the development cohort. RESULTS: In the development cohort, 72 patients (28.7%) were cN(+)pN(-). In multivariable analysis, age ≥ 67 years (odds ratio [OR] 2.85, p = 0.004), right-sided tumor (OR 2.50, p = 0.006), carcinoembryonic antigen ≤ 12 ng/mL (OR 3.11, p = 0.048), cN1 (OR 2.37, p = 0.025), and tumor maximum standardized uptake value ≤ 6.5 (OR 2.03, p = 0.023) were independent predictors for cN(+)pN(-). The prediction model showed a C-index of 0.74 (95% confidence interval [CI] 0.67-0.81), specificity of 94.4%, and positive predictive value (PPV) of 66.7% in the development cohort. In the validation cohort, the C-index was 0.77 (95% CI 0.67-0.86) with good calibration (slope, 1.002; intercept, 0.001), specificity (96.3%), and PPV (70.0%). CONCLUSIONS: In patients with < 4-cm cN(+) NSCLC, a simple model based on five readily available preoperative factors can identify individuals at high risk of false-positive nodal staging with high specificity. This model may help identify patients in whom upfront surgery for definitive pathological nodal evaluation may be preferable rather than immediate neoadjuvant therapy.