The combination of the blood based tumor biomarkers cytokeratin 19 fragments (CYFRA 21-1) and carcinoembryonic antigen (CEA) as a potential predictor of benefit from adjuvant chemotherapy in early stage squamous cell carcinoma of the lung (SCC)

Lung Cancer. 2018 Jun:120:46-53. doi: 10.1016/j.lungcan.2018.03.015. Epub 2018 Mar 17.

Abstract

Objectives: To determine whether the tumor biomarkers cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), which are prognostic in early-stage non-small cell lung cancer (NSCLC), can predict which patients benefit from adjuvant chemotherapy (CTx).

Materials and methods: Serum samples were collected preoperatively from patients with NSCLC who underwent resection. Samples were retrospectively analyzed for CYFRA 21-1 and CEA via electrochemiluminescence immunoassay. Recurrence-free survival (RFS) was compared for patients who received adjuvant CTx versus surgery alone, stratified based on the following prognostic classifications: (1) tumor stage (pT1-2/N0 [stage I] or pT3/N0 or pT1-2/N1 [stage II]), (2) biomarker-based risk score, (3) clinical characteristics. Absolute 2-year RFS rates were calculated via Kaplan-Meier estimations; statistical significance level: 0.05.

Results: 227 patients were included (stage I: 69%; male: 67%; median age 65 years); 70 received adjuvant CTx. Median duration of sample collection was 58.8 months. All high-risk patients (by all three prognostic classifications) who received adjuvant CTx had a longer RFS versus those who received surgery alone. In patients with squamous cell carcinoma (SCC) classified as high risk by all three prognostic classifications, there was a benefit from adjuvant CTx versus surgery alone (tumor stage hazard ratio [HR] 4.9, p = 0.004; biomarker levels HR 9.4, p = 0.002; clinical characteristics HR 9.0, p = 0.003). None of the prognostic classifications were able to predict a benefit from adjuvant CTx in patients with adenocarcinoma.

Conclusion: Baseline CYFRA 21-1 and CEA levels may provide further information to help clinicians decide which patients with SCC should receive adjuvant CTx. Further evaluation of these biomarkers is warranted.

Keywords: Adjuvant chemotherapy; CEA; CYFRA 21-1; NSCLC; Prognosis; Squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoembryonic Antigen / metabolism*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Chemotherapy, Adjuvant*
  • Female
  • Humans
  • Keratin-19 / metabolism*
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Carcinoembryonic Antigen
  • KRT19 protein, human
  • Keratin-19