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Lung-Cancer Screening with Low-Dose Computed Tomography

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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)

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3 thoughts on “Lung-Cancer Screening with Low-Dose Computed Tomography

  1. Some additional links to check out (via email discussions)
    Check this out via Kenny Lin and KevinMD’s blogs:
    http://www.kevinmd.com/blog/2014/12/lung-cancer-screening-shared-decision-making-will-happen.html :
    “Shared decision-making is increasingly recommended by screening guidelines, but I worry that these difficult discussions may not actually take place, even if family physicians are paid to initiate them with patients eligible for LDCT screening. Will clinicians merely go through the motions and just order the test, as happened with prostate-specific antigen testing for prostate cancer and screening mammography for women in their 40s? What do you think?”

    http://www.aafp.org/afp/2014/0715/od3.html#.U8QrZ5BJ84w.twitter
    “The USPSTF recommendation on annual CT-based lung cancer screening should have been given a C grade for now, similar to that for mammography before 50 years of age. This would have encouraged physicians to individualize the decision, taking into account multiple considerations such as comorbid conditions, personal values, and local resources. This would closely parallel the current American Cancer Society recommendations for lung cancer screening.9 The American Academy of Family Physicians also took a more conservative stance in its recent conclusion that there is insufficient evidence for or against CT-based screening in high-risk persons”

    -Clinton

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  2. (additional commentary from emails)

    So, I’m gathering the question you have is, “Should we offer lung cancer screening to some or all patients who smoke in some age group.” Right?

    Several ways to approach the question:
    1) What does a research study say (the approach you’ve taken)
    2) What do guidelines say (which you also seem to have considered)
    3) What is the cost-effectiveness of lung cancer screening? GAH! What’s all this about cost-effectiveness?

    A lot of people confuse cost-effectiveness analysis with cost-benefit analysis, which is how much does something cost in terms of the benefit gained.

    Cost-effectiveness analysis, on the other hand, tries to say how much life is gained in terms of money spent (underlying your question is the real question, “is it worth it?”). See below for a synopsis of a cost-effectiveness analysis based on this study. The study reports the cost per quality-adjusted life-year, a typical outcome that balances quantity and quality of life. A general rule of thumb is that a cost of <$100,000 per QALY is generally “worth it” to society to pay for something.

    Although cost-effectiveneess analysis seems to be a lot of smoke-and-mirrors and the idea of reducing everything to $ does not seem to be right, it’s a good weigh to make decisions about screening and treatment for large populations (i.e., policy decisions). As you have found, though, the average benefit to an individual for lung cancer screening, as it is with most screening tests, is very low.

    -Allen

    http://www.essentialevidenceplus.com/content/poem/170102

    "Lung cancer screening is cost effective, but only if done correctly
    Bottom line
    The United States Preventive Services Task Force (USPSTF) gave lung cancer screening a B recommendation on the basis of the reductions in disease-specific mortality and all-cause mortality seen in the National Lung Screening Trial (NLST). The NLST does not consider cost or cost-effectiveness in its recommendations. This cost-effectiveness analysis suggests that screening is most cost-effective for current smokers, for patients aged in their 60s, and for those who are at higher risk for lung cancer. (LOE = 1b)"

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  3. Hi all,

    Clinton and I looked at the original study and came up with the following answers to your specific questions:

    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?

    This is telling you that, among smokers and former smokers at high risk , mortality is 20% less with screening (relative risk reduction = 20%). There were 1877 deaths among the 26,722 patients screened with CT (7.02%) vs. 2000 deaths among 26,732 in the radiography group (7.48%), a difference of 0.46%. This translates into a number needed to screen of 217 yearly for 3 years to prevent one death due to any cause.

    False positives abound. Each examination is approximately 20 times as likely to yield a false positive as it is to reveal lung cancer.

    This is a characteristic of many screening tests, which sacrifice specificity for sensitivity. For example, only 6% -10% of patients with a positive FOBT will truly have colon cancer. In this case, the false positive rate, across the board, was 96.4% (positive predictive value = 5.6%).

    The risk of overdiagnosis cannot be calculated from this study. In another study (the Mayo Clinic Study of chest x-ray screening) had an overdiagnosis rate of 50% (J Natl Cancer Inst 2006;98(11):748-756)

    Editorial – any of these numbers, taken on its own, can be misleading – that’s why something like cost-effective analysis, which is a type of decision analysis, can be helpful in determining the overall benefit, on average, to certain interventions.

    Clinton and Allen

    Like

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