Prognostic molecular assay might improve identification of patients at risk for recurrence in early-stage non-small-cell lung cancer

Clin Lung Cancer. 2014 Nov;15(6):426-32. doi: 10.1016/j.cllc.2014.07.004. Epub 2014 Aug 15.


Introduction: Adjuvant 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 methods: A 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.

Results: Molecular 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.

Conclusion: This 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.

Keywords: Genetic signature; NCCN guidelines; Recurrence predictors; Risk stratification; Tumor profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling*
  • Humans
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Risk
  • Survival Analysis