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

Authors

Tetsuya Isaka, Yui Kaburaki, Ikki Takada, Ryotaro Matsuyama, Chiaki Kanno, Takuya Nagashima, Yujin Kudo, Yoshihiro Miyata, Morihito Okada, Norihiko Ikeda, Hiroyuki Ito

Published in

BMC cancer. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

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.
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.
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%).
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.

PMID:
42469687
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.

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