Lung Cancer Screening Explained By A Pulmonologist

Lung cancer screening is a process that is used to detect the presence of lung cancer in otherwise healthy people at high risk for cancer. In 2020, 229,000 people will be diagnosed with lung cancer, and 136,000 people will die from the disease, making it the leading cause of cancer death in the U.S.

Data show that screening for lung cancer with low-dose computed tomography (LDCT) reduces the risk of dying from lung cancer in the high-risk population studied. Despite good evidence to support screening, guideline implementation has been slower than optimal.

In 2013, the United States Preventive Services Taskforce (USPSTF) recommended:

• Lung cancer screening using LDCT in people aged 55 to 80 years who are at high risk for developing lung cancer.
• High risk was defined as a 30 pack-year smoking history, current or former smoker, who quit within the last 15 years.

On July 7, 2020, the USFSTF proposed a draft recommendation statement recommending:

• Lung cancer screening using LDCT for people aged 50-80 years who are at high risk for developing lung cancer.
• High risk was defined as people who have smoked at least 20 pack years over their lifetime and still smoke or former smokers who have quit within the last 15 years.

A pack-year calculates how much a person has smoked. One pack-year is equivalent to smoking an average of 20 cigarettes, or one pack, per day for a year.

This change will nearly double the number of people eligible for lung cancer screening (from 8 million to nearly 15 million). This will be especially helpful to African Americans and women.

So the question becomes – why screen? Lung cancer diagnosed without screening or ‘usual care’ has a poor prognosis, with a 5-year survival rate of 20%. However, early-stage non-small cell lung cancer has a much better prognosis.

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So what is the evidence? There are currently 2 randomized controlled trials (RCT) that support lung cancer screening.

The NSLT (the National Lung Cancer Screening Research Trial Team) was conducted between 2002-2011.

• It was a prospective, randomized trial.
• NSLT compared LDCT screening to CXR (chest X-ray) screening for 3 annual screenings.
• It enrolled 53,454 high-risk participants ages 55-74 years with current or former 30 pack-year smoking history or having quit within the last 15 years.
• The endpoint of reduction in lung cancer mortality by 20% was met with a high level of statistical significance, and the study was stopped after a median follow-up of 6.5 years.
• A positive screen was a nodule > 4 mm or other finding related to lung cancer.
• The number of persons needed to screen to prevent 1 lung cancer mortality was 320 persons over 6.5 years.

The American College of Radiology implemented a system called Lung-RADS in April 2014, for risk stratifying the findings on LDCT and standardize recommendations to reduce confusion in screening interpretations and facilitate outcome monitoring. Lung-RADS categories 1 to 2 constitute negative screening results, and categories 3 to 4 constitute positive screen results. An updated version was published in May 2019, which aimed to reduce false positives by downgrading many category 3 findings to category 2 findings.

The NELSON trial (Reduced Lung Cancer Mortality with Volume CT Screening in a Randomized Trial) was published in February 2020. This was the Dutch -Belgian lung cancer screening trial.

• There were 13,195 participants, of whom 85% were male, ages 50 to 74 years.
• They were broken into two groups randomized to usual care vs. screening LDCT at 1 year, 3 years, and 5.5 years.
• At 10 years, the study met statistical significance of reducing lung cancer mortality by 25%.
• The number needed to screen to prevent 1 lung cancer mortality was 130 persons over the screening period.
• The NELSON trial provided empiric evidence for a younger starting age and lighter smoking history.

So what are the harms of screening?

1. False-positive nodules leading to unnecessary tests and invasive procedures.

• Modeling predicts that the new USPSTF criteria would result in 2.2 false-positive results per person screened over a lifetime of screening.
• The NSLT false-positive findings lead to invasive procedures like needle biopsies, bronchoscopies, thoracotomies in 1.7% of patients screened, with complications occurring in 0.1% persons screened.
• It is estimated that 23% of all invasive procedures for false-positive results would be prevented if using Lung-RADS criteria for NSLT.

2. Overdiagnosis of cancer never destined to cause harm

• Modeling predicts 6% of overdiagnosis if new guidelines are implemented.

3. Radiation-induced cancers

• The lifetime risk of cancer from radiation of 10 annual LDCT scan was 3 to 8 major cancers per 10,000 persons screened.
• Modeling predicts the updated guidelines would result in an estimated 39 radiation-related cancer deaths per 100,000 persons (ages 45 to 90 years in the U.S.)

4. Incidental findings other than pulmonary nodules

• Common findings include coronary artery calcifications, aortic aneurysms, emphysema, and possible infections and inflammatory processes.
• The balance of these incidental findings on LDCT remains uncertain.

5. Increased stress and anxiety

• Individuals who receive LDCT screening do not have worse outcomes at 2 years follow-up.

The USPSTF recommends discontinuation of screening if a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have lung surgery.

All people enrolled in a screening program who are current smokers should have smoking cessation interventions.

Shared decision making is important when clinicians and patients discuss screening for lung cancer.

Rizwana Khan is a pulmonary and critical care physician and can be reached at DrKhanMDOnCall.

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