Negative predictive value (NPV) of FDG PET-CT for nodal disease in clinically node-negative early stage lung cancer (AJCC 7^th ed T1-2aN0) and identification of risk factors for occult nodal (pN1-N2) metastasis: implications for SBRT

Non-surgical methods are increasingly employed in the management of early stage lung cancer, but do not afford histological confirmation of nodal status. We sought to assess the incidence, pattern, and predictors of occult nodal involvement (pN1-pN2) in non-small cell lung cancer (NSCLC) patients with negative nodal uptake on fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in early stage lung cancer (clinical stage I AJCC 7^th edition). All patients treated surgically over a 3-year period at Dartmouth Hitchcock Medical Center who were AJCC 7th ed. clinical stage I by pre-operative PET-CT were included in this analysis. The agreement between the clinical stage based on PET-CT and true stage based on pathologic dissection was assessed. Multivariate logistic regression was used to analyze predictors of occult nodal metastasis. Of 144 clinically node-negative patients, 125 were pathologically nodenegative. For all 144 patients, the negative predictive values (NPVs) of PET-CT were 92% for mediastinal disease, 90% for N1 disease, and 87% for overall nodal metastases. The NPVs for mediastinal metastases were 95% in T1 disease and 87% in T2 disease. In multivariate analysis, tumor size (adjusted OR: 3.28, 95% CI: 1.41-7.57), central tumor location (adjusted OR: 7.3, 95% CI: 2.22-24.3), and age at surgery (adjusted OR: 0.95, 95% CI: 0.92-0.98) were significant predictors of occult nodal metastasis. The NPV of PET-CT in nodal staging has implications for the non-surgical treatment of lung cancer, such as stereotactic body radiotherapy, where routine pathologic nodal staging is not performed. Our data suggest PET-CT more accurately rules out the presence of nodal disease in smaller, peripherally located primary tumors.