Screening for Lung Cancer in Current or Past Smokers With Chronic Obstructive Pulmonary Disease

• Proportion of lung cancer that is diagnosed as stage I or II [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  In the control arm, it is expected that only 15% of cancers will be detected early. In the surveillance arm, we expect that at the time of the first screen, the detection rate of prevalence cancers will be about 3%, from data reported in CT screening studies
  
  

• Uptake of screening (the proportion of patients in the surveillance arm who undergo annual screening, among those invited to attend) [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  
• Proportion of patients in the surveillance arm who have abnormal sputum cytology [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  
• Proportion of patients in the surveillance arm who have abnormal sputum cytometry [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  
• Death from lung cancer [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  
• Proportion of failed sputum samples (i.e., where it is not possible to obtain adequate sputum samples) [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  
• Prevalence of pre-invasive disease in patients in the surveillance arm with abnormal cytometry [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  
• Number of patients in the surveillance arm with pre-invasive lesions who develop lung cancer locally and at remote sites within the lung [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• To show that the proportion of lung cancer diagnosed at stage I or II is significantly greater in the surveillance arm than in the control arm.

Secondary

• Establish whether sputum cytology and/or cytometry can be employed to stratify patients with chronic obstructive pulmonary disease (COPD) according to their risk of developing incidence lung cancer.
• Identify patients with pre-invasive lesions in their airways and examine the risk of developing lung cancer in patients harboring these lesions.
• Provide an opportunity to archive blood samples from patients under surveillance to enable the identification of markers of disease progression.
• Examine the compliance of regular screening among patients in this high-risk group.
• Determine the proportion of patients in which it is not possible to provide a sputum screening result.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to recruiting site, age, gender, smoking history (current vs ex-smoker) and severity of chronic obstructive pulmonary disease (COPD) (mild vs moderate). Patients are randomized to 1 of 2 arms.

• Control arm: Patients are managed according to the usual practice of their hospital or general practice for their COPD treatment. They undergo no particular investigations except those that may arise due to a change in their clinical condition. Those patients who are not diagnosed with lung cancer during the course of the study are offered a chest x-ray after 5 years of follow-up.
• Surveillance arm: Patients undergo surveillance for 5 years. A sputum sample is collected for cytology and cytometry. If the sputum sample is normal the patient is asked to provide a sputum sample annually. If the sputum sample is abnormal the patient undergoes an annual spiral CT scan followed by autofluorescence bronchoscopy. At bronchoscopy, the following samples are taken: bronchial washings, bronchial brushings, and bronchial biopsies. Bronchoscopy is repeated every 4-12 months depending upon the histology results. If an invasive lesion is found, the patient is referred for treatment via the normal hospital systems. Any remaining sputum sample is stored frozen as part of the tissue bank associated with this trial.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.