Does lung cancer screening with chest X-ray improve disease-free survival
http://www.100md.com
《血管的通路杂志》
a Department of Cardiothoracic Surgery Centre, Guy's Hospital, St Thomas Street, London, SE1 7EH, UK
b Information Scientist, Royal College of Surgeons of England, Lincolns Inn Fields, London, UK
Abstract
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether screening an asymptomatic person with a routine chest X-ray would detect lung cancer early and, most importantly, improve that person's disease-free survival from lung cancer. Altogether 136 papers were identified using the search below. Ten papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of the papers are tabulated. We conclude that despite methodological criticisms and concerns regarding biases inherent to screening studies, there is currently no evidence to support the use of chest X-ray to screen an asymptomatic person for lung cancer.
Key Words: Evidence-based medicine; Lung neoplasms; Mass screening; Tomography
1. Introduction
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You are a chest registrar seeing a 55-year-old patient in a rapid access out-patient clinic who has recently presented with cough and hemopytsis. He is a smoker and had these symptoms for just a few weeks before being sent for a chest X-ray. It shows a large lesion in the right upper zone. The patient suspects he has lung cancer, which he probably does. He wants to know why he could not have had a chest X-ray before he was sick to pick up his lung cancer.
3. Three part question
In (asymptomatic patients with risk factors for lung cancer) is the use of (Chest X-ray) of benefit in terms of (improved disease-free survival).
4. Search strategy
Medline 1966 – Feb 2006 and Embase 1980 – Feb 2006 using the Dialog Datastar interface [Lung-Neoplasms#.DE. OR Lung-Tumor#.DE. OR (Lung NEAR (Neoplasm$ OR Cancer$ OR Carcinoma$ OR Adenocarcinoma$ OR Angiosarcoma$ OR Chrondosarcoma$ OR Sarcoma$ OR Teratoma$ OR Lymphoma$ OR Blastoma$ OR Microcytic$ OR Carcinogenesis OR Tumor$ OR Tumour$ OR Metast$4)). TI,AB. OR NSCLC.TI,AB. OR SCLC.TI,AB.] AND [Mass-Screening.DE. OR Cancer-Screening.DE. OR (Screen$3 OR Case ADJ Finding OR Casefinding OR Case-Finding).TI,AB.] AND [Radiography-Toracic.DE. OR Mass-Chest-X-Ray.DE. OR Tomography-X-Ray.DE. OR Thorax-Radiography.DE. OR X-Ray.DE.] OR ((Chest OR Thoracic) NEAR (X ADJ Ray$ OR X-Ray$)).TI,AB.] limit to English. This search was repeated in Cochrane Central Register of Controlled Trials.
5. Search outcome
A total of 136 papers were found of which 10 were deemed to be relevant. Only Randomised Control Trials (RCTs) or reviews of RCTs were included. Several systematic reviews and Guidelines for screening were reviewed including the most recent and only meta-analysis on chest X-ray screening. The same group has subsequently updated its previous Cochrane review. The individual randomised trials are presented with the subsequent meta-analysis (Table 1).
6. Comments
The trials reviewed included only male current smokers over 40–45 years of age, and generally assessed more intense screening with chest X-ray±sputum cytology versus less intense chest X-ray screening. Typically the studies tended to show a higher incidence of lung cancer, a higher rate of surgical resection and a better survival in the more intensely screened groups. However, overall there appeared to be no significant reduction in mortality from lung cancer in the intense screening group compared to the less intense screened group. In fact, the subsequent meta-analysis [10] demonstrated that more frequent chest X-ray screening was associated with an 11% relative increase in mortality over less frequent screening. A non-statistically trend to reduced mortality from lung cancer was observed when screening with chest X-ray and sputum cytology was compared to chest X-ray alone (RR 0.88, 95% CI 0.74 to 1.03) [10,14].
The methodology of all the screening studies has been questioned. Criticisms include under-powering of the studies to detect a significant reduction in lung cancer mortality between the groups and adherence to study protocol. Others issues related to biases inherent to screening trials have been suggested to account for this apparent disparity. For example in the Mayo Lung project [6] rates of early tumours in the intense screening group were increased compared to the control group, without altering numbers of advanced cancers detected or mortality rates. This may reflect the fact that intense screening is diagnosing indolent tumours. This is referred to as an over-diagnosis bias, the detection of cancers that would not have become clinically apparent before that person died of other causes.
As well as overdiagnosis bias screening studies may be flawed by other biases; Lead-time bias is where early diagnosis in a screen-detected lung cancer patient falsely appears to prolong survival, despite the actual course of the disease ending in mortality, is the same whether you screen or not. Length bias refers to overestimation of survival duration among screening-detected lung cancer caused by the relative excess of slowly progressing cases. Screening over-represents less aggressive disease. Thus, a comparison between screen-detected lung cancer and others detected by the person developing symptoms or signs appears to overestimate benefit because the former consists of cases that were diagnosed earlier, progress more slowly, and may never become clinically relevant. Such biases all appear to inflate the survival of screen-detected cases
7. Clinical bottom line
The current evidence does not support the use of chest X-ray (with or without sputum cytology) as a screening test for lung cancer.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact J Cardiovasc Thoracic Surg 2003; 2:405–409.
Brett GZ. The value of lung cancer detection by six-monthly chest radiographs. Thorax 1968; 23:414–420.
Wilde J. A 10 year follow-up of semi-annual screening for early detection of lung cancer in the Erfurt County, GDR. Eur Respir J 1989; 2:656–662.
Frost JK, Ball WC Jr, Levin ML, Tockman MS, Baker RR, Carter D, Eggleston JC, Erozan YS, Gupta PK, Khouri NF. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev Respir Dis 1984; 130:549–554.
Fontana RS, Sanderson DR, Taylor WF, Woolner LB, Miller WE, Muhm JR, Uhlenhopp MA. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Respir Dis 1984; 130:561–565.
Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller WE, Muhm JR, Bernatz PE, Payne WS, Pairolero PC, Bergstralh EJ. Screening for lung cancer. A critique of the Mayo Lung Project. Cancer 1991; 67:1155–1164.
Berlin NI. Overview of the NCI Cooperative Early Lung Cancer Detection Program. Cancer 2000; 89:2349–2351.
Melamed MR. Lung cancer screening results in the National Cancer Institute New York study. Cancer 2000; 89:2356–2362.
Kubik A, Polak J. Lung cancer detection. Results of a randomised prospective study in Czechoslovakia. Cancer 1986; 57:2427–2437.
Manser RL, Irving LB, Byrnes G, Abramson MJ, Stone CA, Campbell DA. Screening for lung cancer: a systematic review and meta-analysis of controlled trials. Thorax 2003; 58:784–789.
Screening for lung cancer. Cochrane Database Syst Rev CD001991, 2004 Manser RL, Irving LB, Stone C, Byrnes G, Abramson M, Campbell D.
Bach PB, Kelley MJ, Tate RC, McCrory DC. Screening for lung cancer: a review of the current literature. Chest 2003; 123:72S–82S.
Bach PB, Niewoehner DE, Black WC. Screening for lung cancer: the guidelines. Chest 2003; 123:83S–88S.
Lung cancer screening: recommendation statement. Ann Intern Med 2004; 140:738–739.
Oken MM, Marcus PM, Hu P, Beck TM, Hocking W, Kvale PA, Cordes J, Riley TL, Winslow SD, Peace S, Levin DL, Prorok PC, Gohagan JK. Baseline chest radiograph for lung cancer detection in the randomised Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. J Natl Cancer Inst 2005; 97:1832–1839.(Ian Hunt, Mayooran Siva, )
b Information Scientist, Royal College of Surgeons of England, Lincolns Inn Fields, London, UK
Abstract
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether screening an asymptomatic person with a routine chest X-ray would detect lung cancer early and, most importantly, improve that person's disease-free survival from lung cancer. Altogether 136 papers were identified using the search below. Ten papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of the papers are tabulated. We conclude that despite methodological criticisms and concerns regarding biases inherent to screening studies, there is currently no evidence to support the use of chest X-ray to screen an asymptomatic person for lung cancer.
Key Words: Evidence-based medicine; Lung neoplasms; Mass screening; Tomography
1. Introduction
A best evidence topic was constructed according to a structured protocol. This protocol is fully described in the ICVTS [1].
2. Clinical scenario
You are a chest registrar seeing a 55-year-old patient in a rapid access out-patient clinic who has recently presented with cough and hemopytsis. He is a smoker and had these symptoms for just a few weeks before being sent for a chest X-ray. It shows a large lesion in the right upper zone. The patient suspects he has lung cancer, which he probably does. He wants to know why he could not have had a chest X-ray before he was sick to pick up his lung cancer.
3. Three part question
In (asymptomatic patients with risk factors for lung cancer) is the use of (Chest X-ray) of benefit in terms of (improved disease-free survival).
4. Search strategy
Medline 1966 – Feb 2006 and Embase 1980 – Feb 2006 using the Dialog Datastar interface [Lung-Neoplasms#.DE. OR Lung-Tumor#.DE. OR (Lung NEAR (Neoplasm$ OR Cancer$ OR Carcinoma$ OR Adenocarcinoma$ OR Angiosarcoma$ OR Chrondosarcoma$ OR Sarcoma$ OR Teratoma$ OR Lymphoma$ OR Blastoma$ OR Microcytic$ OR Carcinogenesis OR Tumor$ OR Tumour$ OR Metast$4)). TI,AB. OR NSCLC.TI,AB. OR SCLC.TI,AB.] AND [Mass-Screening.DE. OR Cancer-Screening.DE. OR (Screen$3 OR Case ADJ Finding OR Casefinding OR Case-Finding).TI,AB.] AND [Radiography-Toracic.DE. OR Mass-Chest-X-Ray.DE. OR Tomography-X-Ray.DE. OR Thorax-Radiography.DE. OR X-Ray.DE.] OR ((Chest OR Thoracic) NEAR (X ADJ Ray$ OR X-Ray$)).TI,AB.] limit to English. This search was repeated in Cochrane Central Register of Controlled Trials.
5. Search outcome
A total of 136 papers were found of which 10 were deemed to be relevant. Only Randomised Control Trials (RCTs) or reviews of RCTs were included. Several systematic reviews and Guidelines for screening were reviewed including the most recent and only meta-analysis on chest X-ray screening. The same group has subsequently updated its previous Cochrane review. The individual randomised trials are presented with the subsequent meta-analysis (Table 1).
6. Comments
The trials reviewed included only male current smokers over 40–45 years of age, and generally assessed more intense screening with chest X-ray±sputum cytology versus less intense chest X-ray screening. Typically the studies tended to show a higher incidence of lung cancer, a higher rate of surgical resection and a better survival in the more intensely screened groups. However, overall there appeared to be no significant reduction in mortality from lung cancer in the intense screening group compared to the less intense screened group. In fact, the subsequent meta-analysis [10] demonstrated that more frequent chest X-ray screening was associated with an 11% relative increase in mortality over less frequent screening. A non-statistically trend to reduced mortality from lung cancer was observed when screening with chest X-ray and sputum cytology was compared to chest X-ray alone (RR 0.88, 95% CI 0.74 to 1.03) [10,14].
The methodology of all the screening studies has been questioned. Criticisms include under-powering of the studies to detect a significant reduction in lung cancer mortality between the groups and adherence to study protocol. Others issues related to biases inherent to screening trials have been suggested to account for this apparent disparity. For example in the Mayo Lung project [6] rates of early tumours in the intense screening group were increased compared to the control group, without altering numbers of advanced cancers detected or mortality rates. This may reflect the fact that intense screening is diagnosing indolent tumours. This is referred to as an over-diagnosis bias, the detection of cancers that would not have become clinically apparent before that person died of other causes.
As well as overdiagnosis bias screening studies may be flawed by other biases; Lead-time bias is where early diagnosis in a screen-detected lung cancer patient falsely appears to prolong survival, despite the actual course of the disease ending in mortality, is the same whether you screen or not. Length bias refers to overestimation of survival duration among screening-detected lung cancer caused by the relative excess of slowly progressing cases. Screening over-represents less aggressive disease. Thus, a comparison between screen-detected lung cancer and others detected by the person developing symptoms or signs appears to overestimate benefit because the former consists of cases that were diagnosed earlier, progress more slowly, and may never become clinically relevant. Such biases all appear to inflate the survival of screen-detected cases
7. Clinical bottom line
The current evidence does not support the use of chest X-ray (with or without sputum cytology) as a screening test for lung cancer.
References
Dunning J, Prendergast B, Mackway-Jones K. Towards evidence-based medicine in cardiothoracic surgery: best BETS. Interact J Cardiovasc Thoracic Surg 2003; 2:405–409.
Brett GZ. The value of lung cancer detection by six-monthly chest radiographs. Thorax 1968; 23:414–420.
Wilde J. A 10 year follow-up of semi-annual screening for early detection of lung cancer in the Erfurt County, GDR. Eur Respir J 1989; 2:656–662.
Frost JK, Ball WC Jr, Levin ML, Tockman MS, Baker RR, Carter D, Eggleston JC, Erozan YS, Gupta PK, Khouri NF. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev Respir Dis 1984; 130:549–554.
Fontana RS, Sanderson DR, Taylor WF, Woolner LB, Miller WE, Muhm JR, Uhlenhopp MA. Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Respir Dis 1984; 130:561–565.
Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller WE, Muhm JR, Bernatz PE, Payne WS, Pairolero PC, Bergstralh EJ. Screening for lung cancer. A critique of the Mayo Lung Project. Cancer 1991; 67:1155–1164.
Berlin NI. Overview of the NCI Cooperative Early Lung Cancer Detection Program. Cancer 2000; 89:2349–2351.
Melamed MR. Lung cancer screening results in the National Cancer Institute New York study. Cancer 2000; 89:2356–2362.
Kubik A, Polak J. Lung cancer detection. Results of a randomised prospective study in Czechoslovakia. Cancer 1986; 57:2427–2437.
Manser RL, Irving LB, Byrnes G, Abramson MJ, Stone CA, Campbell DA. Screening for lung cancer: a systematic review and meta-analysis of controlled trials. Thorax 2003; 58:784–789.
Screening for lung cancer. Cochrane Database Syst Rev CD001991, 2004 Manser RL, Irving LB, Stone C, Byrnes G, Abramson M, Campbell D.
Bach PB, Kelley MJ, Tate RC, McCrory DC. Screening for lung cancer: a review of the current literature. Chest 2003; 123:72S–82S.
Bach PB, Niewoehner DE, Black WC. Screening for lung cancer: the guidelines. Chest 2003; 123:83S–88S.
Lung cancer screening: recommendation statement. Ann Intern Med 2004; 140:738–739.
Oken MM, Marcus PM, Hu P, Beck TM, Hocking W, Kvale PA, Cordes J, Riley TL, Winslow SD, Peace S, Levin DL, Prorok PC, Gohagan JK. Baseline chest radiograph for lung cancer detection in the randomised Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. J Natl Cancer Inst 2005; 97:1832–1839.(Ian Hunt, Mayooran Siva, )