Therapeutics
Review: Low-dose CT screening reduces lung cancer and mortality in current or former smokers
Humphrey LL, Deffebach M, Pappas M, et al. Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive Services Task Force recommendation. Ann Intern Med. 2013;159:411-20.
Clinical impact ratings: F ★★★★★★✩ p ★★★★★✩✩ Question In asymptomatic current or former smokers, what are the benefits and harms of low-dose computed tomography (LDCT) for lung cancer screening?
*Humphrey L, Deffebach M, Pappas M, et al. Screening for lung cancer: systematic review to update the US Preventive Services Task Force recommendation. Evidence Synthesis No. 105. AHRQ Publication No. 13-05188-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2013.
Review scope
Source of funding: Agency for Healthcare Research and Quality.
Included English-language studies published after 2000 that compared LDCT with chest radiography or usual care in {≥ 1000}* asymptomatic adults {≥ 18 years of age}* who were current or former smokers. Outcomes included lung cancer mortality and all-cause mortality.
For correspondence: Dr. L.L. Humphrey, Oregon Health & Science University, Portland, OR, USA. E-mail [email protected]. ■
Commentary The publication of the National Lung Screening Trial (NLST) (1) moved the discussion about lung cancer screening from the efficacy of LDCT screening of former smokers to the policy implications regarding which specific populations should be screened. Indeed, there seems to be consensus that screening a subgroup of former smokers for lung cancer will have definite clinical benefit (1, 2). The review by Humphrey and colleagues analyzed lung cancer screening trials and shows that only the NLST had the ability to fully evaluate the effectiveness of lung cancer screening due to its power and randomized design. The other 3 RCTs were lacking in numbers or follow-up or had other design issues.
Review methods MEDLINE (2000 to May 2013); Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (both to Oct 2012); Scopus; and reference lists were searched for studies and systematic reviews. 7 randomized controlled trials (RCTs) and 13 cohort studies met selection criteria. 4 RCTs reported LDCT and comparison group results (n = 64 129, age range 49 to 74 y, 55% to 100% men, median follow-up range 34 mo to 6.5 y, mean pack-y range 36 to 56) and are reported in this abstract; 2 had unclear allocation concealment, 1 had inadequate randomization, and 3 had differential follow-up between groups. Meta-analyses were not done due to study heterogeneity.
Over the past 2 years, most major professional organizations involved in lung cancer have recommended screening of highvolume smokers > 55 and < 74 years of age (3-5).
Main results
The review by Humphrey and colleagues raises concerns about lung cancer screening, including the possible effects of radiation exposure, anxiety from cancer diagnosis and false-positive results, and fear that patients will ignore smoking cessation efforts once they have a negative CT scan. For lung cancer screening to be effective, it must adhere to the guidelines throughout the process and be supported by a well-trained multidisciplinary team that includes radiology, surgery, and medicine to ensure that screening is done in a methodical and comprehensive manner.
The main results are in the Table. In the largest RCT, LDCT reduced lung cancer and all-cause mortality (Table).
Conclusion In asymptomatic current or former smokers, low-dose computed tomography for lung cancer screening reduces lung cancer and total mortality. Low-dose computed tomography (LDCT) screening for lung cancer vs chest radiography or usual care (control) in current or former smokers† Outcomes
Lung cancer mortality
All-cause mortality
Trial
n
Event rates/ At 34 mo to 6.5 y 100 000 person-y LDCT Control RRR/RRI (95% CI) NNS
NLST‡
53 454
247
309
RRR 20% (7 to 27)
320
DANTE§
2472
527
637
RRR 17% (−54 to 55)
NS
DLCST||
4104
154
112
RRI 37% (−37 to 197)
NS
MILD¶
2913
216
109
RRI 99% (−20 to 396)
NS
NLST‡
53 454
1142
1216
RRR 7% (1 to 14)
219
DANTE§
2472
1212
1433
RRR 15% (−27 to 44)
NS
DLCST||
4104
625
429
RRI 46% (−1 to 115)
NS
MILD¶
2913
558
310
RRI 80% (3 to 313)
NR
†DANTE = Detection and Screening of Early Lung Cancer by Novel Imaging Technology and Molecular Essays; DLCST = Danish Lung Cancer Screening Trial; MILD = Multi-centric Italian Lung Detection; NLST = National Lung Screening Trial; NNS = number needed to screen; NR = not reported; NS = not significant; other abbreviations defined in Glossary. RRR, RRI, and CI calculated from relative risks in article. ‡LDCT vs chest radiography. §LDCT vs annual clinic review. ||LDCT vs usual care.
Christopher Lathan, MD, MS, MPH David A. Frank, MD, PhD Dana-Farber Cancer Institute, Harvard Medical School Boston, Massachusetts, USA Reference 1. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409. 2. US Preventive Services Task Force. Screening for lung cancer: Draft recommendation statement. AHRQ Publication No. 1305196-EF-www.uspreventiveservicestaskforce.org/uspstf13/ lungcan/lungcandraftrec.htm (accessed 24 Sep 13). 3. Wood DE, Eapen GA, Ettinger DS, et al. Lung cancer screening. J Natl Compr Canc Netw. 2012;10:240-65. 4. Jacobson FL, Austin JH, Field JK, et al. Development of the American Association for Thoracic Surgery guidelines for low-dose computed tomography scans to screen for lung cancer in North America: recommendations of the American Association for Thoracic Surgery Task Force for Lung Cancer Screening and Surveillance. J Thorac Cardiovasc Surg. 2012;144:25-32. 5. Wender R, Fontham ET, Barrera E Jr, et al. American Cancer Society lung cancer screening guidelines. CA Cancer J Clin. 2013;63:107-17.
¶Annual LDCT vs biennial LDCT vs usual care (n = 4099). Results for annual LDCT vs usual care are presented (n = 2913).
19 November 2013 | ACP Journal Club | Volume 159 • Number 10
© 2013 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/928838/ by a NYU Medical Center Library User on 04/19/2017
JC3
Review: Low-dose CT screening reduces lung cancer and mortality in current or former smokers
Humphrey LL, Deffebach M, Pappas M, et al. Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive Services Task Force recommendation. Ann Intern Med. 2013;159:411-20.
Clinical impact ratings: F ★★★★★★✩ p ★★★★★✩✩ Question In asymptomatic current or former smokers, what are the benefits and harms of low-dose computed tomography (LDCT) for lung cancer screening?
*Humphrey L, Deffebach M, Pappas M, et al. Screening for lung cancer: systematic review to update the US Preventive Services Task Force recommendation. Evidence Synthesis No. 105. AHRQ Publication No. 13-05188-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2013.
Review scope
Source of funding: Agency for Healthcare Research and Quality.
Included English-language studies published after 2000 that compared LDCT with chest radiography or usual care in {≥ 1000}* asymptomatic adults {≥ 18 years of age}* who were current or former smokers. Outcomes included lung cancer mortality and all-cause mortality.
For correspondence: Dr. L.L. Humphrey, Oregon Health & Science University, Portland, OR, USA. E-mail [email protected]. ■
Commentary The publication of the National Lung Screening Trial (NLST) (1) moved the discussion about lung cancer screening from the efficacy of LDCT screening of former smokers to the policy implications regarding which specific populations should be screened. Indeed, there seems to be consensus that screening a subgroup of former smokers for lung cancer will have definite clinical benefit (1, 2). The review by Humphrey and colleagues analyzed lung cancer screening trials and shows that only the NLST had the ability to fully evaluate the effectiveness of lung cancer screening due to its power and randomized design. The other 3 RCTs were lacking in numbers or follow-up or had other design issues.
Review methods MEDLINE (2000 to May 2013); Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (both to Oct 2012); Scopus; and reference lists were searched for studies and systematic reviews. 7 randomized controlled trials (RCTs) and 13 cohort studies met selection criteria. 4 RCTs reported LDCT and comparison group results (n = 64 129, age range 49 to 74 y, 55% to 100% men, median follow-up range 34 mo to 6.5 y, mean pack-y range 36 to 56) and are reported in this abstract; 2 had unclear allocation concealment, 1 had inadequate randomization, and 3 had differential follow-up between groups. Meta-analyses were not done due to study heterogeneity.
Over the past 2 years, most major professional organizations involved in lung cancer have recommended screening of highvolume smokers > 55 and < 74 years of age (3-5).
Main results
The review by Humphrey and colleagues raises concerns about lung cancer screening, including the possible effects of radiation exposure, anxiety from cancer diagnosis and false-positive results, and fear that patients will ignore smoking cessation efforts once they have a negative CT scan. For lung cancer screening to be effective, it must adhere to the guidelines throughout the process and be supported by a well-trained multidisciplinary team that includes radiology, surgery, and medicine to ensure that screening is done in a methodical and comprehensive manner.
The main results are in the Table. In the largest RCT, LDCT reduced lung cancer and all-cause mortality (Table).
Conclusion In asymptomatic current or former smokers, low-dose computed tomography for lung cancer screening reduces lung cancer and total mortality. Low-dose computed tomography (LDCT) screening for lung cancer vs chest radiography or usual care (control) in current or former smokers† Outcomes
Lung cancer mortality
All-cause mortality
Trial
n
Event rates/ At 34 mo to 6.5 y 100 000 person-y LDCT Control RRR/RRI (95% CI) NNS
NLST‡
53 454
247
309
RRR 20% (7 to 27)
320
DANTE§
2472
527
637
RRR 17% (−54 to 55)
NS
DLCST||
4104
154
112
RRI 37% (−37 to 197)
NS
MILD¶
2913
216
109
RRI 99% (−20 to 396)
NS
NLST‡
53 454
1142
1216
RRR 7% (1 to 14)
219
DANTE§
2472
1212
1433
RRR 15% (−27 to 44)
NS
DLCST||
4104
625
429
RRI 46% (−1 to 115)
NS
MILD¶
2913
558
310
RRI 80% (3 to 313)
NR
†DANTE = Detection and Screening of Early Lung Cancer by Novel Imaging Technology and Molecular Essays; DLCST = Danish Lung Cancer Screening Trial; MILD = Multi-centric Italian Lung Detection; NLST = National Lung Screening Trial; NNS = number needed to screen; NR = not reported; NS = not significant; other abbreviations defined in Glossary. RRR, RRI, and CI calculated from relative risks in article. ‡LDCT vs chest radiography. §LDCT vs annual clinic review. ||LDCT vs usual care.
Christopher Lathan, MD, MS, MPH David A. Frank, MD, PhD Dana-Farber Cancer Institute, Harvard Medical School Boston, Massachusetts, USA Reference 1. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409. 2. US Preventive Services Task Force. Screening for lung cancer: Draft recommendation statement. AHRQ Publication No. 1305196-EF-www.uspreventiveservicestaskforce.org/uspstf13/ lungcan/lungcandraftrec.htm (accessed 24 Sep 13). 3. Wood DE, Eapen GA, Ettinger DS, et al. Lung cancer screening. J Natl Compr Canc Netw. 2012;10:240-65. 4. Jacobson FL, Austin JH, Field JK, et al. Development of the American Association for Thoracic Surgery guidelines for low-dose computed tomography scans to screen for lung cancer in North America: recommendations of the American Association for Thoracic Surgery Task Force for Lung Cancer Screening and Surveillance. J Thorac Cardiovasc Surg. 2012;144:25-32. 5. Wender R, Fontham ET, Barrera E Jr, et al. American Cancer Society lung cancer screening guidelines. CA Cancer J Clin. 2013;63:107-17.
¶Annual LDCT vs biennial LDCT vs usual care (n = 4099). Results for annual LDCT vs usual care are presented (n = 2913).
19 November 2013 | ACP Journal Club | Volume 159 • Number 10
© 2013 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/928838/ by a NYU Medical Center Library User on 04/19/2017
JC3
