Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group

Eur Respir J. 2019 Oct 17;54(4):1900581. doi: 10.1183/13993003.00581-2019. Print 2019 Oct.

Abstract

Background: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy.

Methods: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell).

Results: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively.

Conclusions: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / complications
  • Adenocarcinoma of Lung / diagnostic imaging
  • Adenocarcinoma of Lung / pathology
  • Bronchoscopy
  • Carcinoma, Large Cell / complications
  • Carcinoma, Large Cell / diagnostic imaging
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Small Cell / complications
  • Carcinoma, Small Cell / diagnostic imaging
  • Carcinoma, Small Cell / pathology*
  • Carcinoma, Squamous Cell / complications
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / pathology
  • Cytological Techniques
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Lung Neoplasms / complications
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Optical Imaging
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Risk Assessment
  • Sensitivity and Specificity
  • Sputum / cytology*
  • Tomography, X-Ray Computed
  • United Kingdom