The National Comprehensive Cancer Network (NCCN) Guidelines recommend that patients with early-stage non-small cell lung cancer (NSCLC) be treated with adjuvant chemotherapy post-surgical resection if they are high-risk. The NCCN notes certain clinicopathologic features as examples of what could be considered as high-risk; however, these clinicopathologic features have never been validated to stratify risk or predict chemotherapy benefit. A CLIA-certified, commercially available 14-gene quantitative PCR expression assay (DetermaRx) has been extensively validated to assess mortality risk in early-stage non-squamous NSCLC (Lancet 2012; 379:823). In a non-randomized single-institution prospective cohort, the 14-gene molecular risk classifier was superior to the NCCN high-risk features in assessing mortality risk, and predicted benefit from chemotherapy in stages I-IIA (Clinical Lung Cancer 2018; 19:58).
Clinical factors, pathology, and molecular risk profiles of all non-squamous NSCLC specimens received for testing with the 14-gene expression assay in a CLIA certified laboratory (Razor Genomics) between 2/3/2020 and 8/19/2020 were analyzed. Pathologic stage and the type and number of NCCN high-risk clinicopathologic features (poorly differentiated tumor, vascular invasion, wedge resection, tumor size >4cm, visceral pleural involvement, unknown lymph node status) were obtained from the pathology reports submitted with the specimens for testing.
One hundred and forty cases were available for analysis. Specimens were sent from a total of 22 community and academic medical centers; two-thirds of cases were from a community setting. Forty-five (32%) of cases were resulted as molecular high- or intermediate-risk by the 14-gene expression assay. More than half (59%) of all specimens received were stage IA according to AJCC 8th edition staging criteria, and one-fourth of these stage IA cases were found to be molecular high/intermediate-risk. Molecular high/intermediate-risk cases were more likely to have at least one NCCN high-risk feature compared to molecular low-risk (82% vs. 52%). However, 57% of cases that would have been considered high-risk by NCCN (defined as having at least one high-risk feature) were reclassified as low-risk by the molecular assay, and 15% of cases that had no NCCN high-risk features were reclassified as molecular high-risk.
Clinical adoption trends reveal that molecular risk classification is being utilized in the early-stage setting, particularly for stage IA patients. An extensively validated 14-gene expression assay that has previously been demonstrated to outperform NCCN high-risk features in assessing mortality risk reclassifies traditional clinicopathologic feature-based risk for many early-stage patients in the clinical setting.
early-stage, biomarkers, adjuvant therapy
© 2021 Published by Elsevier Inc.