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Lung-Cancer Screening with Low-Dose Computed Tomography

Bonjou, zanmi!  Today, in Journal Club, we discussed:

Lung-Cancer Screening with Low-Dose Computed Tomography

Gould, MK. NEJM 6 Nov 2014 pp1813-1820

The issue:

Lung CA is the leading cause of death from cancer in both men and women in the US. Despite the advances of modern medicine, only 18% of patients with lung CA are still alive 5 years after diagnosis. Early trials of chest x-rays and sputum screening don’t decrease lung cancer mortality. This engendered studies worldwide that demonstrated the sensitivity of CT scanning, particularly the low dose varieties that reduce radiation by 75-80% (but are still 10-15 times higher than plain films). The pitfalls of these studies are that they were vulnerable to lead-time bias (read: same mortality, earlier diagnosis) and overdiagnosis.

The data:

The National Lung Screening Trial enrolled 50,000 people at 33 US centers who were:

  • 55-74 years of age
  • At least 30 pack year hx
  • If a former smoker, had to have quit within previous 15 years

Randomly assigned to three rounds of annual screening with low-dose CT vs chest radiography. 20% reduction in lung cancer mortality was shown (247 vs 309 deaths per 100,000 patient-years) which translated into 3 fewer deaths from lung CA per 1000 high risk patients who underwent low-dose CT screening. This magnitude of benefit is at least as great as that reported for breast cancer mortality with annual (not biennial) mammo screening among women 50-59 years of age. Which is to say, more lead-time bias.

Of course: 39% of the participants had at least one positive result, and more than 95% of these findings were falsely positive. 10% of participants underwent tissue sampling. This adds to the data that show the reduction in lung-cancer mortality observed in the NLST is not as clear as the author is purporting.

Funky stuff:

  • USPSTF jumped on the bandwagon in Dec 2013 and released a grade B recommendation in favor of annual low-dose CT screening for high risk patients (55-80 w/ 30py smoking hx who are either currently smoking or quit within the last 15 years).
  • Conflicting committee opinions on how to apply the NLST data have resulted in how Medicare will cover this.
  • The greatest benefits of screening are found in those at highest risk for death from lung cancer, who, really, have the least to gain from screening than those at low risk!

Conclusions we drew from the conclusions

  • Annual lung cancer screening of high risk and former smokers with low dose CT mirrors annual breast cancer screening in 50-59 year old women with mammography. i.e. increases lead time bias without making a real impact on our patients’ qualities of life.
  • Though the article’s recs say that screening with low-dose CT prevents one in five deaths from lung cancer, we can’t fiddle with the numbers to make this work. Fellows: could you help us with this?
  • Lung cancer screening is NOT a single test, it is ANNUAL testing and the article makes no judgment about cost-effectiveness.
  • False positives Each examination is approximately 20 times as likely to yield a false positive as it is to reveal lung cancer.
    • Of those false positives, 5% will require invasive evaluation.
  • No surprise here: screening for lung CA with low dose CT is not a substitute for smoking cessation.

EBM points:

Always look for the NNT on these things. Per The NNT (http://www.thennt.com/nnt/ct-scans-to-screen-for-lung-cancer/)

1 in 217 are helped (prevented death)
1 in 4 were harmed by false positive
1 in 30 were harmed by unnecessary surgery
1 in 161 were harmed by surgical complication

Per the NNT: “…Despite these caveats the significant and surprisingly large reduction in mortality using CT screening in this trial is promising. Because this is the first high quality randomized trial of CT screening it will take multiple further trials to confirm the benefit, and it will be critical to apply these data only to people at very high risk unless future trials expand to include others.”.

I dunno, y’all, our discussion made me more negative about it than The NNT seems to think.

Danielle (PGY-3)