Prognostic Molecular Assay Might Improve Identification of Patients At Risk for Recurrence in Early-Stage Non–Small-Cell Lung Cancer

Abstract

IntroductionAdjuvant chemotherapy improves survival for some patients with NSCLC and is recommended in NCCN guidelines for stage Ib to IIa patients with certain “high-risk” characteristics. An internationally validated, 14-gene expression assay has been shown to better stratify mortality risk in nonsquamous NSCLC than either conventional staging or these high risk clinicopathologic features. Patients and MethodsA blinded chart review of 52 patients with prospective molecular risk stratification using the 14-gene test compared recurrence outcomes with a mean follow-up of 15.2 ± 11.7 months of patients with high- or low-risk determined according to either NCCN criteria or the molecular assay. ResultsMolecular risk assessment was discordant from NCCN criteria in 14 of 23 patients in stages Ib and IIa (61%). Recurrence was not observed among any of 31 molecular intermediate- or low-risk patients, including 10 NCCN high-risk patients, whereas 2 of 6 recurrences (33%) occurred among NCCN low-risk patients. Recurrences in stages I or IIa were seen in 2 of 18 NCCN high-risk patients (11%; both were stage IIa and both received a high-risk molecular designation), and in 4 of 18 patients (22%) with a high-risk molecular score, including 1 stage Ia and 1 stage Ib patient. ConclusionThis small cohort study suggests that a 14-gene prognostic assay more accurately stratifies risk among early-stage NSCLC patients than current NCCN criteria. NCCN guidelines already advocate risk stratification within tumor, node, metastases stages. This molecular assay has clinical utility in better identifying high-risk patients and might improve NCCN adjuvant chemotherapy recommendations.