What is the accuracy of clinical staging for stage III-single station N2 NSCLC? A multi-centre UK study

Introduction Single station N2 (ssN2) versus multistation N2 (msN2) has been used a selection criterion for treatment recommendations between surgical versus non-surgical multimodality treatment in stage III-N2 non-small cell lung cancer (NSCLC). We hypothesised that clinical staging would be prone to upstaging on pathological staging and, therefore, challenge this practice. Methods A retrospective study of prospectively collected routine clinical data for patients with stage III-N2 NSCLC that had completed CT, PET and staging EBUS and had been confirmed clinical stage III-ssN2 at MDT discussion and went on to complete surgical resection as first treatment to provide pathological staging. The study was completed in two cohorts A) across a single cancer alliance in England (Greater Manchester) 01/01/2015 – 31/12/2018 and B) across five UK centres to validate the findings in part A 01/01/2016 – 31/12/2020. Results A total of 115 patients met the inclusion criteria across Cohort A (56 patients) and Cohort B (59 patients) across 15 UK hospitals. The proportion of cases in which clinical stage III-ssN2 was upstaged to pathological stage III-msN2 was 34% (19/56) in cohort A, 32% in cohort B (19/59) and 33% across the combined study cohort (38/115). The majority of patients had a single radiologically abnormal lymph node on CT and PET (88%, 105/115). In the majority, the reasons for missed N2 disease on staging EBUS were due to inaccessible (stations 5, 6, 8, 9) N2 nodes at EBUS (34%, 13/38) and accessible lymph nodes not sampled during staging EBUS as not meeting sampling threshold (40%, 15/38) rather than false negative sampling during EBUS (26%, 10/38). Discussion During MDT discussions, clinicians must be aware that one third of patients with stage III-ssN2 based on CT, PET and staging EBUS do not truly have ssN2 and this questions the use of this criterion to define treatment recommendations.