WCLC 2019 – A non-invasive complementary biomarker improves the efficacy of lung cancer screening

  • Elena Riboldi — Agenzia Zoe
  • Univadis
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  • The combination of blood microRNA (miRNA) assay and low-dose computed tomography (LDCT) allows optimal screening intensity and reduces unnecessary LDCT repeats in lung cancer (LC) screening.


Why this matters

  • Screening by LDCT can reduce LC-specific mortality.
  • Adequate risk stratification is needed to choose the optimal screening interval.


Study design

  • The bioMILD trial prospectively enrolled 4119 volunteers; inclusion criteria were: aged 50-75, ≥30 pack-years, smoking stop ≤10 years.
  • At baseline, participants received LDCT and miRNA profiling.
  • LDCT threshold cut-off was set at 113 mm3.
  • The 24-miRNA signature classifier predicts 3 risk levels; subjects were defined miRNA-negative if classified at low risk or miRNA-positive if classified at intermediate/high risk.
  • LDCT and miRNA were tested independently with blind evaluation.
  • Participants were grouped into 3 categories: double positive (2-pos: LDCT-positive and miRNA-positive), single positive (1pos: LDCT-positive or miRNA-positive), double negative (2neg: LDCT-negative and miRNA-negative).
  • LDCT screening intervals were: 3-6 months (2pos), 1 year (1pos), 3 years (2neg).
  • Median observation period was 4.5 years.


Key results

  • Participants in the 2neg, 1pos, and 2pos groups were 2384 (58%), 1526 (37%), and 209 (5%), respectively.
  • After four screening runs, 115 LCs were diagnosed (2.8%).
  • Cumulative LC incidence was significantly different in the three groups: 0.6% for 2neg subjects, 3.8% for 1pos and 20.1% for 2pos (P
  • LC incidence within 3 years in the three groups was 0.1%, 2.5%, and 19.1%, respectively (P
  • LC risk was significantly higher in 1-pos and 2-pos subjects (HR 6.0 and 36.6, respectively).
  • LC mortality in the three groups was 0.1%, 0.6% and 3.8%, respectively (P
  • LC mortality was significantly higher in 1-pos and 2-pos subjects (HR 5.7 and 32.2, respectively).
  • Interval cancer incidence, proportion of stage I, and resected LC were not statistically different among groups.



  • Italian Association for Cancer Research (AIRC), Italian Ministry of Health, National Cancer Institute of Milan, US National Institutes of Health, Gensignia.


Expert commentary

“Reducing regular follow-up scans based on additional risk information is a way forward, but prospective large randomised clinical trials are needed to confirm safety of these approaches in nationwide programs.” Harry J. de Koning, MD, PhD, Erasmus MC (Rotterdam, Netherlands).