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

Study Overview
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Brief Summary
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RATIONALE: Screening tests or exams may help doctors find lung cancer sooner, when it may be easier to treat. PURPOSE: This randomized clinical trial is studying screening tests or exams to see how well they work compared to usual care in finding early stage lung cancer in current or past smokers with chronic obstructive pulmonary disease.

Detailed Description
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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.

Official Title
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A Randomised Controlled Trial of Surveillance for the Early Detection of Lung Cancer in an at Risk Group [Lung-SEARCH Trial]

Conditions
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Lung Cancer, Precancerous Condition

Intervention / Treatment
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* Other: cytology and cytometry specimen collection procedure
* Other: Chest x ray
* Procedure: Autofluorescence bronchoscopy
* Procedure: CT scan


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Inclusion criteria: Meets 1 of the following criteria: Current smoker, defined as ≥ a 20 pack year smoking history and/or 20 year duration of smoking Ex-smoker who has quit smoking within the past 8 years AND has ≥ a 20 pack year smoking history and/or 20 year duration of smoking Mild to moderate chronic obstructive pulmonary disease (COPD) as defined by the GOLD criteria Mild COPD: FEV_1/forced vital capacity (FVC) < 70%; FEV_1 ≥ 80% of predicted* Moderate COPD: FEV_1/FVC < 70%; FEV_1 50-80% of predicted* NOTE: *Spirometric values will be obtained post bronchodilator according to the recommendations in the GOLD criteria Exclusion criteria: Inadequate lung function (FEV_1 < 50% of predicted after bronchodilator) PATIENT CHARACTERISTICS: Inclusion criteria: Life expectancy must be at least 5 years Exclusion criteria: History of malignant disease within the past 5 years except non-melanomatous skin cancers Other serious co-morbidity Evidence of severe or uncontrolled systemic diseases that, in the view of the investigator, makes it undesirable for the patient to participate in this trial Any disorder making reliable informed consent impossible Unlikely to co-operate with a 5 year follow-up PRIOR CONCURRENT THERAPY: Patients may receive all concurrent therapy deemed to provide adequate care as decided by their medical doctors
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Surveillance<br>Screened arm | Other: cytology and cytometry specimen collection procedure<br>* Samples tested and further interventions added if positive<br>Other: Chest x ray<br>* Patients not diagnosed with lung cancer during the course of the study, will be offered an exit chest x-ray after 5 years or sooner if they withdraw from the trial before 5 years. This could help identify a lung cancer that may not have been associated with symptoms earlier.<br>Procedure: Autofluorescence bronchoscopy<br>* The bronchial tree will be inspected first under white light and then under blue light. All areas that appear abnormal will initially be documented and only sampled when the bronchoscopic examination has been completed.<br>* Other names: AFB;Procedure: CT scan<br>* All patients with abnormal sputum cytology and/or cytometry will undergo low dose spiral CT without contrast.<br>|
| Active Comparator: Control<br>Control arm | Other: Chest x ray<br>* Patients not diagnosed with lung cancer during the course of the study, will be offered an exit chest x-ray after 5 years or sooner if they withdraw from the trial before 5 years. This could help identify a lung cancer that may not have been associated with symptoms earlier.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of lung cancer that is diagnosed as stage I or II | 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 | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uptake of screening (the proportion of patients in the surveillance arm who undergo annual screening, among those invited to attend) |  | 5 Years | 
| Proportion of patients in the surveillance arm who have abnormal sputum cytology |  | 5 Years | 
| Proportion of patients in the surveillance arm who have abnormal sputum cytometry |  | 5 Years | 
| Death from lung cancer |  | Up to 15 years | 
| Proportion of failed sputum samples (i.e., where it is not possible to obtain adequate sputum samples) |  | 5 Years | 
| Prevalence of pre-invasive disease in patients in the surveillance arm with abnormal cytometry |  | 5 Years | 
| Number of patients in the surveillance arm with pre-invasive lesions who develop lung cancer locally and at remote sites within the lung |  | 5 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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small cell lung cancer, non-small cell lung cancer, precancerous condition