Does lung cancer screening with Chest X-ray improve disease-free survival?
Date First Published:
April 12, 2006
Last Updated:
September 20, 2006
Report by:
Ian Hunt, Mayooran Siva, Rachel Southon, Tom Treasure, Specialist Registrar in Emergency Medicine (Department of thoracic Surgery, Guy's Hospital, Royal College of Surgeons of England,)
Search checked by:
Joel Dunning, Department of thoracic Surgery, Guy's Hospital, Royal College of Surgeons of England,
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]
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.
Search Strategy:
Medline 1966 – Feb 2006 and Embase 1980 – Feb 2006 using the Dialog Datastar interface
Search Details:
[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.
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
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| The value of lung cancer detection by six-monthly chest radiographs. Brett GZ. 1960-1962 UK | N=55034 Males 40 Smokers and non-smokers |
Cluster RCT | Resectability of patients with lung cancer | 6 monthly CXR (I) 29% versus CXR at entry and exit of study (C) 44% | Limitation of screening biases Comparison is between intensive versus less intensive screening patients |
| Disease specific 5-year survival | 5-year survival of patients with lung cancer for intervention 15% over control group 6% | ||||
| Lung cancer mortality in population per 1000 patients/year | No benefit shown between intervention (0.7) over control group (0.8) RR (screen group/control) was 1.03 (95% CI, 0.74–1.42) | ||||
| A 10 year follow-up of semi-annual screening for early detection of lung cancer in the Erfurt County, GDR. Wilde J. 1972-1977 Germany | N=104880 Males aged 40-65 years Smokers and non-smokers |
Cluster RCT | Resectability of patients with lung cancer | 6 monthly CXR (I) 28% vs. 18 monthly CXR (C) 19% | Limitation of screening biases Compliance with scheduled screening was not described in detail |
| Disease specific 5-year survival | 5-year survival of patients with lung cancer for intervention 14% over control group 8% | ||||
| Lung cancer mortality in population per 1000 patients/year | No benefit shown between intervention (0.6) over control group (0.8) RR (screen group/control) was 1.34 (95% CI, 0.94–1.98) | ||||
| Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Frost JK, Ball WC Jr, Levin ML, Tockman MS, Baker RR, Carter D, Eggleston JC, Erozan YS, Gupta PK, Khouri NF. 1973-1978 USA | N=10384 Males 45 |
RCT | Lung cancer detection rate in population per 1000 patients/year | Annual CXR and 4 monthly sputum 4.8 versus annual CXR 5.5 | Comparison is between intensive versus less intensive screening patients Adherence to strict protocol was poor |
| Resectability of patients with lung cancer | Annual CXR & 4-monthly sputum (I) 4.8% versus annual CXR (C) 5.5% | ||||
| Disease specific 5-year survival | 5-year survival of patients with lung cancer for intervention 47% over control group 44% | ||||
| Lung cancer mortality in population per 1000 patients | No benefit shown between intervention (0.6) over control group (0.8) RR (screen group/control) was 0.80 (95% CI, 0.65–1.00) | ||||
| Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Fontana RS, Sanderson DR, Taylor WF, Woolner LB, Miller WE, Muhm JR, Uhlenhopp MA. 1971-1976 | N=10933 Males 45 Heavy smokers |
RCT | Lung cancer detection rate in population per 1000 patients/year | 4 monthly CXR and sputum 4.5 versus advised annual CXR and sputum 3.5 | Lung cancer mortality is higher in intervention group compared to control group due to possible over diagnosis bias Comparison is between intensive versus less intensive screening patients |
| Resectability of patients with lung cancer | 4 monthly CXR and sputum (I) 4.5% versus annual CXR and sputum (C) 3.5% | ||||
| Disease specific 5-year survival | 5-year survival of patients with lung cancer for intervention 46% over control group 32% | ||||
| Overview of the NCI Cooperative Early Lung Cancer Detection Program. Berlin NI. 1974-1978 USA | N=10040 Age >45 years old Smokers |
RCT | Resectability of patients with lung cancer | Annual CXR and sputum (I) 53% versus annual CXR (C) 51% | |
| Disease specific 5-year survival | 5-year survival of patients with lung cancer for intervention 37% over control group 33% | ||||
| Lung cancer mortality in population per 1000 patients/year | No benefit shown between intervention (2.7) over control group (2.7) RR (screen group/control) was 0.98 (95% CI, 0.76–1.26) | ||||
| Lung cancer detection. Results of a randomised prospective study in Czechoslovakia. Kubik A, Polak J. 1976-1982 Czechoslovakia | N=6364 Males aged 40-64 years Current heavy smokers |
RCT | Resectability of patients with lung cancer | 6-monthly CXR years 1, 2, 4 and annual CXR years 4, 5, 6 (I) 25% versus CXR years 4, 5, 6 (C) 16% | No unscreened control group |
| Disease specific 5-year survival | 5-year survival of patients with lung cancer for intervention 26% over control group 0% | ||||
| Lung cancer mortality in population per 1000 patients/year | No benefit shown between intervention (1.7) over control group (1.5) RR (screen group/control) was 1.14 (95% CI, 0.96–1.36) | ||||
| Screening for lung cancer: a systematic review and meta-analysis of controlled trials. Manser RL, Irving LB, Byrnes G, Abramson MJ, Stone CA, Campbell DA. 2003 and 2004 Australia | N=245 610 Aged > 40 years old |
A systematic review and meta-analysis of controlled trials | Lung cancer mortality was significantly greater in the group undergoing more frequent CXR than in those receiving less frequent screening (p=0.05) | More frequent CXR screening was associated with an 11% relative increase in mortality over less frequent screening (RR 1.11, 95% CI, 1.00 to 1.23)<br><br>A non-statistically trend to reduced mortality from lung cancer was observed when screening with CXR and sputum cytology was compared to CXR alone (RR 0.88, 95% CI 0.74 to 1.03) | Most of the trials reviewed excluded women, young patients <45 years old and ex-smokers |
| Screening for lung cancer: the guidelines. Bach PB, Niewoehner DE, Black WC. 2003 and 2003 USA | Review of 5 RCTs comparing CXR±sputum cytology versus control | Non-systematic review | Prolonged life expectancy of individual with disease | Neither CXR and/or sputum was of benefit | Review not systematic with no further statistical analysis |
| Test not harmful or painful | Not addressed in sufficient detail in any of the studies reviewed | ||||
| Lung cancer screening:recommendation statement. U.S. Preventive Services Task Force, Agency for Healthcare Research and Quality 2004 USA | Systematic review and guideline of 6 RCTs and 1 non-RCT comparing CXR ± sputum cytology versus control having searched Medline from 1966 to 2003 | Systematic review and guideline | Studies were graded according to criteria developed by USPSTF | None of the 6 CXR ± sputum cytology RCTs showed benefit among those screened<br><br>All studies were limited because some level of screening occurred in control group<br><br>4 control-studies from Japan suggested benefit to both high and low risk participants, with screening using CXR ± sputum cytology occurring within 1 year of diagnosis, OR range 0.4–0.72 | |
| Baseline chest radiograph for lung cancer detection in the randomised Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. 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. 2005 USA | 154942 participants aged 55-74 years with no history of PLCO cancer, randomly assigned to an intervention arm (77465) | RCT, baseline screen report | Number of initial suspicious CXR | 8.9% (9.5% CI = 8.7%–9.2%) (N=5991) CXRS suspicious for Lung cancer, 206 (3.4%, 95% CI=3–3.9%) biopsies, 126 (61.2%, 95% CI=54.5–67.8%) diagnosed with lung cancer | |
| Number of lung cancers detected per 1000 screens | 1.9 lung cancers were detected per 1000 screens, with positive predictive value 2.1% (95% CI=1.7–2.5%) | ||||
| Number of lung cancers detected per 1000 screens of smokers or ex-smokers | 6.3 lung cancers were detected per 1000 screens, amongst current smoker; and 4.9 per 1000 screens amongst ex-smokers (less than 15 years) | ||||
| Detection of early stage lung cancer | Among cancers diagnosed, 44% (95% CI=35–52%) were stage I NSCLC |
Author Commentary:
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 [Manser] 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) [Manser, U.S. Preventive Services Task Force].
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:
- Brett GZ.. The value of lung cancer detection by six-monthly chest radiographs.
- Wilde J.. A 10 year follow-up of semi-annual screening for early detection of lung cancer in the Erfurt County, GDR.
- 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.
- 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.
- 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.
- Berlin NI.. Overview of the NCI Cooperative Early Lung Cancer Detection Program.
- Melamed MR.. Lung cancer screening results in the National Cancer Institute New York study.
- Kubik A, Polak J.. Lung cancer detection. Results of a randomised prospective study in Czechoslovakia.
- 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.
- Manser RL, Irving LB, Stone C, Byrnes G, Abramson M, Campbell D.. Screening for lung cancer.
- Bach PB, Kelley MJ, Tate RC, McCrory DC.. Screening for lung cancer: a review of the current literature.
- Bach PB, Niewoehner DE, Black WC.. Screening for lung cancer: the guidelines.
- U.S. Preventive Services Task Force, Agency for Healthcare Research and Quality. Lung cancer screening:recommendation statement.
- 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.