False-negative rate after positron emission tomography/computer tomography scan for mediastinal staging in cI stage non-small-cell lung cancer

Abstract

To assess the false-negative (FN) rate of positron emission tomography (PET)-chest computed tomography (CT) scan in clinical non-central cIA and cIB non-small-cell lung cancer (NSCLC) for mediastinal staging. Between January 2007 and December 2010, 402 patients with potentially operable NSCLC were assessed by thoracic CT scan and 18-fluoro-2-deoxy-d-glucose PET-CT for mediastinal staging and to detect extrathoracic metastases, of which 153 surgically treated patients (79 cIA and 74 cIB cases) were prospectively included in the study. Central tumours were excluded on the basis of CT scan criteria, defined as contact with the intrapulmonary main bronchi, pulmonary artery, pulmonary veins or the origin of the first segmental branches. CT scan was considered negative if lymph nodes were <1 cm at the smaller diameter. 18FDG PET-CT was considered negative when the high maximum standard uptake value (SUVmax) was <2.5. Non-invasive surgical staging was carried out in this group, and curative resection plus systematic mediastinal dissection was performed except in the event of unexpected oncological contraindication. Composite non-invasive staging (CT scan, PET-CT) showed a negative predictive value (NPV) of 92% (CI 83.6-96.8) in the cIA group and 85% (CI 74-92) in the cIB group. There were 6 of 79 (7.6%) false-negatives (FNs) in cIA and 11 of 74 (14.8%) in cIB. Multilevel pN2 were detected in four cases, all of them in the cIB group. The most frequently involved N2 was subcarinal (two cases) in cIA and right lower paratracheal (R4) and seven (five cases) in cIB. Occult (pN2) lymph nodes were more frequent in tumour sizes≥5 cm (pT2b, nine cases, four FNs, P=0.03), pN1, adenocarcinoma [excluding minimally invasive adenocarcinoma (MIA) and lepidic predominant growth (LPA)] (P=0.029) and female patients, but no other risk factors for mediastinal metastases were identified (age, clinical stage, tumour location, central or peripheral, P>0.05). Multilevel pN2 was significantly more frequent in the cIB group (P<0.03). In pT≤1 cm (T1a), NPV was significantly better (NPV=100%, P<0.05) than the other subgroups studied (IA>1 cm and IB). Composite results for non-invasive mediastinal staging (CT scan, PET-CT) showed 11% of FNs in cI stage (7.6% in non-central cIA and 14.8% in cIB). In tumours≤1 cm, NPV makes surgical staging unnecessary. In women with adenocarcinoma and non-central cIB, however, the high FN rate makes invasive staging necessary, particularly in pT2b to decrease the incidence of unexpected pN2 in thoracotomy.