To Screen or Not to Screen? When Screening for Lung Cancer Causes Harm and How Physicians Can Avoid Overscreening

In a standing-room-only educational session at the 2014 meeting of the American College of Chest Physicians in Austin, Texas, Gerard A. Silvestri, MD, MS, a professor at the Medical University of South Carolina, discussed the state of the art in lung cancer screening.

Screening is different from other population health measures in that screening is not an activity for patients. Rather, it is an intervention for healthy individuals that may help a physician detect and ultimately treat a disease. Lung cancer is a good candidate for broad, population-based screening because it is a common disease with a high mortality rate that is often more successfully treated when a diagnosis is established early in the disease process.

At the same time, screening should never be misconstrued as universally beneficial. Unfortunately, many patients and physicians in the United States hold the mistaken view that screening patients for cancer is consistent with the principle of “do no harm.”

In an article published by Schwartz et al in the Journal of the American Medical Association, investigators surveyed members of the public who had never had cancer to determine in what situations individuals would and would not be willing to undergo screening.1 Of 500 individuals surveyed, including women 40 years or older and men 50 years or older, more than one-third (38%) of respondents reported having experienced at least 1 false-positive result on a diagnostic test intended to detect cancer. Of those who experienced a false positive, the majority (80%) described the experience as either “very scary” or “the scariest time of my life.” Regardless of the unpleasantness of that experience, 98% of respondents who experienced a false-positive test result did not regret undergoing the test.¹

Even if nothing could be done to improve their prognosis, two-thirds of those surveyed would rather know they had cancer than not know. “People love screening in the United States,” noted Dr Silvestri, but with screening comes the risk of overtesting, overtreating, and potentially harming patients.¹

Physicians are also at risk for overzealous screening for cancer. In a study published in 2012 by Leach et al in the journal Cancer,² investigators assessed whether or not physicians would recommend mammography screening for women with terminal illness. Of 1196 physicians queried, approximately two-thirds (67.5%) responded to the survey. Nearly half of primary care physicians reported that they would recommended mammography screening for women aged 50 to 80 years with terminal lung cancer. Addressing the physician audience, Dr Silvestri concluded, “If you think that there is no controversy over screening, you are sadly mistaken.” For instance:

• In a 154,901-participant study of chest x-ray screening among patients aged 55 to 74 years randomized to chest x-ray screening or a sham procedure, and followed up over a period of 4 years, chest x-ray was found to be ineffective for lung cancer screening.³
• A 76,693-patient study of screening interventions to detect prostate cancer found that after 7 to 10 years of follow-up, screening did not improve survival.⁴
• In a 39,111-patient study, ovarian cancer screening with vaginal ultrasound led to 3285 false-positive test results, which led to 1080 follow-up surgical procedures. Of these surgeries, 15% resulted in serious complications, which were needless given that screening did not improve mortality outcomes. In fact, there were numerically more deaths due to ovarian cancer in the screening group than in the usual care group (2.6 per 10,000 person-years vs 3.1 per 10,000 person-years).⁵
• A 44,925-patient study of mammography over 5 years conducted in Canadian health centers found no benefit of mammography in terms of death from breast cancer after 25 years of follow-up (hazard ratio: 1.05; 95% CI: 0.85-1.30).⁶

According to Dr Silvestri, “About 22% of cancers are overdiagnosed...and this is consistent across virtually every type of solid tumor.” In other words, of cancers detected by screening, nearly 1 in 4 screening-detected cancers would never affect the patient’s life expectancy.

Not all of the results of screening trials are negative. In the 53,439-patient National Lung Screening Trial (NLST), low-dose helical computed tomography (CT) led to a higher rate of early-stage lung cancer diagnoses than chest x-ray in high-risk patients (those aged 55 to 74 years with a 30 pack-year smoking history). These results correspond with an approximately 6.7% reduction in mortality. Approximately 3 lung cancers would be detected for every 1000 people screened with low-dose CT.⁷

These benefits, however, could be outweighed by the potential harm of lung biopsy after low-dose helical CT is used to identify the presence of a suspected tumor. Approximately 1% of lung biopsies result in bleeding episodes requiring transfusion, and 15% of procedures may result in pneumothorax (a collapsed lung).

Given all these data, the risks and benefits of screening must be weighed carefully. One method to weigh the decision of whether or not to screen is risk stratification. For instance, Kovalchik and colleagues reanalyzed data from the NLST and divided patients into quintiles of risk based on their likelihood of developing lung cancer. False-positive rates and number-needed-to-screen rates were calculated for each quintile of individuals. The 20% of patients with the highest risk of developing lung cancer had the lowest rate of false-positive diagnoses, and the number of patients needed to screen to detect 1 case of lung cancer was 161—a remarkably low number.⁸

This research points the way forward in lung cancer screening. Patients should be assessed for their risk of developing lung cancer (through a simple online calculator based on population data) and be told of their risk, and physicians should discuss screening as an option based on that risk score. In this way, physicians can find the patients who are most likely to benefit from cancer screening, insuring the least possible harm through false-positive test results, the maximal benefit for high-risk patients, and the most responsible use of healthcare resources.

References

1. Schwartz LM, Woloshin S, Fowler FJ Jr, Welch HG. Enthusiasm for cancer screening in the United States. JAMA. 2004;291(1):71-78.
2. Leach CR, Klabunde CN, Alfano CM, Smith JL, Rowland JH. Physician over-recommendation of mammography for terminally ill women. Cancer. 2012;118(1):27-37.
3. Oken MM, Hocking WG, Kvale PA, et al; PLCO Project Team. Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA. 2011;306(17):1865-1873.
4. Andriole GL, Crawford ED, Grubb RL 3rd, et al; PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360(13):1310-1319.
5. Buys SS, Partridge E, Black A, et al; PLCO Project Team. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295-2303.
6. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014;348:g366.
7. National Lung Screening Trial Research Team; Church TR, Black WC, Aberle DR, et al. Results of initial low-dose computed tomographic screening for lung cancer. N Engl J Med. 2013;368(21):1980-1991.
8. Kovalchik SA, Tammemagi M, Berg CD, et al. Targeting of low-dose CT screening according to the risk of lung-cancer death. N Engl J Med. 2013;369(3):245-254.