Assessment of the External Validity of the National Comprehensive Cancer Network and European Society for Medical Oncology Guidelines for Non-Small-Cell Lung Cancer in a Population of Patients Aged 80 Years and Older

Clin Lung Cancer. 2017 Sep;18(5):460-471. doi: 10.1016/j.cllc.2017.03.005. Epub 2017 Mar 21.


Non-small-cell lung cancer (NSCLC) is a disease of the elderly, who are under-represented in clinical trials. This challenges the external validity of the evidence base for its management and of current guidelines, that we evaluated in a population of older patients. We retrieved randomized clinical trials (RCTs) supporting the guidelines and identified 18 relevant topics. We matched a cohort of NSCLC patients aged older than 80 years from the Moffitt Cancer Center database with the studies' eligibility criteria to check their qualification for at least 2 studies. Eligibility > 60% was rated full validity, 30% to 60% partial validity, and < 30% limited validity. We obtained data from 760 elderly patients in stage-adjusted groups and collected 244 RCTs from the National Comprehensive Cancer Network (NCCN) and 148 from the European Society for Medical Oncology (ESMO) guidelines. External validity was deemed insufficient for neoadjuvant chemotherapy in stage III disease (27.37% and 25.26% of patients eligible for NCCN and ESMO guidelines, respectively) and use of bevacizumab (13.86% and 16.27% of patients eligible). For ESMO guidelines, it was inadequate regarding double-agent chemotherapy (25.90% of patients eligible), its duration (24.10%) and therapy for Eastern Cooperative Oncology Group performance status 2 patients (17.74%). For NCCN guidelines external validity was lacking for neoadjuvant chemoradiotherapy in stage IIIA disease (25.86% of patients eligible). Our analysis highlighted the effect of RCT eligibility criteria on guidelines' external validity in elderly patients. Eligibility criteria should be carefully considered in trial design and more studies that do not exclude elderly patients should be included in guidelines.

Keywords: Elderly; External validity; Geriatric oncology; Guidelines; NSCLC.

Publication types

  • Review

MeSH terms

  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Bevacizumab / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemoradiotherapy, Adjuvant
  • Chemotherapy, Adjuvant
  • Evidence-Based Medicine
  • Humans
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Patient Selection*
  • Practice Guidelines as Topic / standards*
  • Randomized Controlled Trials as Topic / standards*


  • Antineoplastic Agents
  • Bevacizumab