Week 4 – NLST

“Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening”

by the National Lung Cancer Screening Trial Research Team

N Engl J Med. 2011 Aug 4;365(5):395-409 [NEJM free full text]

Despite a reduction in smoking rates in the United States, lung cancer remains the number one cause of cancer death in the United States, as well as worldwide. Earlier studies of plain chest radiograph for lung cancer screening demonstrated no benefit, and thus in 2002 the National Lung Screening Trial (NLST) was undertaken to determine whether then-recent advances in CT technology could lead to an effective lung cancer screening method.

Population: adults age 55-74 with 30+ pack-years of smoking (if former smokers, they must have quit within the past 15 years)
Intervention: three annual screenings for lung cancer with low-dose CT
Comparison: three annual screenings for lung cancer with PA chest radiograph
Outcome: 1º = mortality from lung cancer, 2º = mortality from any cause and incidence of lung cancer

Results/Conclusion:
53,454 patients were randomized, and both groups had similar baseline characteristics. The low-dose CT group demonstrated 247 deaths from lung cancer per 100,000 person-years, whereas the radiography group demonstrated 309 deaths per 100,000 person-years. Thus a relative reduction in rate of death by 20.0% was seen in the CT group (95% CI 6.8 – 26.7%, p = 0.004). The number needed to screen with CT to prevent one lung cancer death was 320. There were 1877 deaths from any cause in the CT group and 2000 deaths in the radiography group; thus CT screening demonstrated a risk reduction of death from any cause of 6.7% (95% CI 1.2% – 13.6%, p = 0.02). Incidence of lung cancer in the CT group was 645 per 100,000 person-years and 941 per 100,000 person-years in the radiography group (RR 1.13, 95% CI 1.03 – 1.23).

Implication/Discussion:
Lung cancer screening with low-dose CT scan in high-risk patients provides a significant mortality benefit.

This trial was stopped early because the mortality benefit was so high. The benefit was driven by the reduction in deaths attributed to lung cancer – and when deaths from lung cancer were excluded from the overall mortality analysis there was no significant difference among the two arms. Largely on the basis of this study, the 2013 USPSTF guidelines for lung cancer screening recommend annual low-dose CT scan in patients who meet NLST inclusion criteria.

Per UpToDate, there are seven low-dose CT screening trials in progress in Europe. It is hoped that meta-analysis of all such RCTs will allow for further refinement in risk stratification, frequency of screening, and management of positive screening findings.

Of note, no randomized trial has ever demonstrated a mortality benefit of chest radiography for lung cancer screening. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial tested this modality vs. “community care,” and because the PLCO trial was ongoing at the time of creation of the NSLT, the NSLT authors trial decided to compare their intervention (CT) to chest radiography, in case the results of chest radiography in PLCO were positive (ultimately they were not).

Further Reading:
1. USPSTF Guidelines for Lung Cancer Screening (2013)
2. ClinicalTrials.gov
3. Wiki Journal Club
4. 2 Minute Medicine

Summary by Duncan F. Moore, MD

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