Medical Policy: 06.01.19
Original Effective Date: February 2003
Reviewed: February 2020
Revised: February 2020
This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.
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This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Lung cancer is the leading cause of cancer related mortality in the United States and worldwide. In 2019, it is estimated that 142,670 deaths (76,650 in men and 66,020 in women) from lung cancer will occur in the United States, which is about 24% of all the U.S. deaths from cancer. Five-year survival rates for lung cancer are only 19%, partly because most patients have advanced stage lung cancer at initial diagnosis. These facts combined with the success of screening in improving outcomes in patients with cervical, colon and breast cancers have been the impetus for studies to develop an effective lung cancer screening test. Ideally, effective screening will lead to earlier detection of lung cancer (before patients have symptoms and when treatment is more likely to be effective) and will decrease mortality. Currently, most lung cancer is diagnosed clinically when patients present with symptoms such as persistent cough, pain and weight loss; unfortunately patients with these symptoms usually have advanced lung cancer. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low dose CT (LDCT) of the chest to screen select patients who are at high risk for lung cancer (NCCN Version 1.2020).
The goal of screening is to detect disease at a stage when it is not causing symptoms and when treatment will be most successful. Screening should benefit the individual by increasing life expectancy and increasing quality of life. The rate of false-positive results should be low to prevent unnecessary additional testing. The large fraction of the population without the disease should not be harmed (low risk), and the screening test should not be so expensive that it places an onerous burden on the health care system. Thus, the screening test should: 1) improve outcomes; 2) be scientifically validated (e.g. have acceptable levels of sensitivity and specificity; and 3) be low risk, reproducible, accessible and cost-effective (NCCN Version 1.2020).
Chest x-ray (CXR) and sputum cytology have been the most common methods used for screening lung cancer, but previous studies have failed to demonstrate that screening with these modalities resulted in improved health outcomes. More recently, low-dose computed tomography (LDCT) has been proposed as a method of screening asymptomatic, high risk individuals for lung cancer. LDCT refers to a non-contrast study with a multi-detector CT scanner during a single maximal inspiratory breath-hold with a scanning time of under 25 seconds. New multi-detector CT scanners generate high-resolution imaging with radiation exposure significantly less than for diagnostic CT scanning. It has been suggested that LDCT may be an improved early lung cancer detection tool based on the advantages it appears to have over CXR and sputum cytology to detect lung cancer at an earlier stage.
Shared patient and physician decision making may be the best approach before deciding whether to do LDCT lung cancer screening, especially for patients with comorbid conditions. Individuals who choose to undergo lung cancer screening should enter an organized screening program at an institution with expertise in LDCT screening, with access to a multidisciplinary team skilled in the evaluation, diagnosis and treatment of abnormal lung lesions.
While screening for lung cancer has the potential benefits of decreased morbidity and mortality from lung cancer it also has potential harms, which include:
The National Lung Screening Trial (NLST) was a randomized trial sponsored by the National Institute of Health comparing the annual screening by low dose computed tomography (LDCT) scanning with standard chest x-ray for three years in 53, 454 high risk individuals at 33 United States medical centers. Participants were men and women 55 to 74 years of age with a history of at least 30 pack years of smoking, current smokers and those who had discontinued smoking within 15 years of enrollment. In 2013, the NLST researchers released their findings which found approximately 15 to 20 percent fewer lung cancer deaths among trial participants screened with low dose computed tomography (LDCT) compared to the participants screened with chest x-ray. The trial was stopped early after an interim analysis found a statistically significant benefit for low dose computed tomography scanning.
In 2013, a study by Kovalchik et. al. investigated whether the benefits and harms of low-dose CT screening in the NLST participants differed according to the participants' prescreening risk of lung cancer death. The participants were classified into two groups, a CT-screening group and a radiography group, and then into five quintiles for the predicted 5-year risk of death from lung cancer (with quintile 1 having the lowest risk and quintile 5 having the highest risk). The median follow-up was 5.5 years. The number of lung-cancer deaths per 10,000 person-years that were prevented in the CT-screening group when compared to the radiography group increased with risk quintile (0.2 in quintile 1, 3.5 in quintile 2, 1in quintile 3, 11.0 in quintile 4, and 12.0 in quintile 5; P=0.01 for trend). There were decreasing trends in the number of false positive results per screening-prevented lung-cancer death (1648 in quintile 1, 181 in quintile 2, 147 in quintile 3, 64 in quintile 4, and 65 in quintile 5). Subjects with the highest risk for lung-cancer death (quintiles 3 through 5) accounted for 88% of the screening-prevented lung-cancer deaths and for 64% of participants with false positive results. The 20% of participants at lowest risk (quintile 1) accounted for only 1% of prevented lung-cancer deaths. The authors concluded that "Screening with low-dose CT prevented the greatest number of deaths from lung cancer among participants who were at highest risk and prevented very few deaths among those at lowest risk."
A 2017 study by Rampinelli et.al. reported on the cumulative radiation exposure and lifetime attributable risk of cancer in those scanned with low-dose CT scans. In this retrospective review, 5203 asymptomatic, high-risk participants underwent annual low-dose CT scan for 10 consecutive years. High-risk status was defined as age greater than 50 years old, smoking history with greater than or equal to 20 pack-years, and no history of cancer in the past 5 years. The numbers of additional cancers cases induced by 10 years of screening was 1.5 lung cancers and 2.4 major cancers, an additional risk of induced major cancers of 0.05% (2.4/5,203). The authors concluded, "Radiation exposure and cancer risk from low dose CT screening for lung cancer, even if non-negligible, can be considered acceptable in light of the substantial mortality reduction associated with screening."
In 2019, Huang et. al. conducted a systematic review and meta-analysis to update the evidence of low dose computed tomography (LDCT) in lung cancer screening. The NELSON mortality results were presented in September 2018. Four other randomized control trials (RCTs) also reported the latest mortality outcomes in 2018 and 2019. Studies included met all of the following criteria: (1) only randomized controlled trials; (2) comparing LDCT to any other type of lung cancer screening; (3) adults, aged > 18 years, asymptomatic with risk factor for lung cancer (current or former smokers, family history of lung cancer, underlying lung disease, or environmental exposure to toxins); (4) benefits of interest included: lung cancer mortality, all-cause mortality, early detection (stage I) rates; (5) harms of interest included: death and major complications after invasive procedures (30–60 days post invasive procedures). Major complications were listed below: death, anaphylaxis, cardiac arrest, cerebral vascular accident/stroke, congestive heart failure, myocardial infarction, intervention-required thromboembolic complications, acute respiratory failure, respiratory arrest, bronchial stump leak requiring tube thoracostomy or other drainage for > 4 days, bronchopulmonary fistula, empyema, prolonged mechanical ventilation > 48 h postoperatively, tube placement-required hemothorax, brachial plexopathy, lung collapse, chylous fistula, injury to vital organ or vessel, wound dehiscence, and infarcted sigmoid colon. Invasive procedures included: surgery, biopsy, bronchoscopy or fine needle aspiration cytology.
Nine randomized controlled trials (RCTs) (with multiple publications) met the inclusion criteria. These RCTs contributed to lung cancer mortality outcomes. When compared with controls (no screening or CXR), LDCT screening was associated with a statistically significant reduction in lung cancer mortality (RR 0.83, 95% CI 0.76–0.90) with no heterogeneity observed (p = 0.43, I2 = 1%). Trial sequential analysis (TSA) confirmed that the conclusion for lung cancer mortality was sufficient and no more trials were needed. Seven included trials contributed information on all-cause mortality. On the contrary, LDCT screening demonstrated no statistically significant difference in all-cause mortality (RR 0.95, 95% CI 0.90–1.00). There was no heterogeneity with this outcome (I2 = 0%). Pooled analysis of seven RCTs showed significantly greater proportions (RR 2.08, 95% CI 1.43–3.03) of early stage cancers in LDCT groups compared to controls.
As to the harm of screening, two studies reported number of deaths after invasive procedures for diagnosis purpose. Nineteen deaths were reported after 2129 invasive procedures in persons screened by LDCT and 11 deaths were reported after 792 invasive procedures in the control group. No significant difference (RR 0.64, 95% CI 0.30–1.33¸ I2 = 0) was shown. Only one study (NLST) reported major complication rates following invasive procedures for LDCT and CXR group. The risk was higher among persons who underwent LDCT compared with CXR screening (4.1 vs 3.2 per 10,000 screened).
In the subgroup analysis according to study quality, compared with controls, LDCT screening demonstrated a statistically significant reduction in lung cancer mortality among high quality studies (RR 0.82, 95% CI 0.73–0.91). However, the same situation has not been observed in low quality studies (RR 0.87, 95% CI 0.64–1.20, I2 = 23%). This suggests that trial quality might be a potential source of heterogeneity. They furthered explored the heterogeneity on the basis of sample size and conducted a subgroup analysis based on the different sample size. A sample size that is too small reduces the power of the trial and increases the margin of error, which can render the trial meaningless. Pooled analysis of findings from seven fairly small trials (total n = 27,968) comparing LDCT with controls showed no significant difference in lung cancer mortality. While findings from two large trials (NELSON, NLST; total n = 69,276), the results of the pooled data displayed a RR of 0.80 (95% CI 0.71–0.91). In addition, regardless male or female, LDCT showed a reduction of lung cancer mortality. Sensitivity analyses were robust. The positive association was consistent with any of these analyses. Reliability and stability of our conclusions were further confirmed.
This is the first meta-analysis of LDCT for lung cancer screening based on sufficient evidence demonstrated by trial sequential analysis (TSA) with the latest NELSON, MILD and LUSI mortality results included. NELSON trial is the only European fully powered RCT which presented its 10-year mortality findings in September 2018 at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC). In total, nine RCTs are included. Most RCTs (DANTE, DLCST, ITALUNG, LUSI, MILD, NELSON) are conducted in European countries, some trials are conducted in the USA (LSS, NLST) and China (Yang 2018). The majority of included studies are judged to be of moderate to high quality (some concerns and low risk of bias for mortality outcomes), but two studies (DANTE, MILD) are judged to be of low quality (high risk of bias for mortality outcomes). Pooled results comparing LDCT to no screening or CXR establish a survival benefit and show an increase in detection of stage I cancers. As for harms of lung cancer screening, LDCT leads to an increase in the frequency of invasive procedures but does not lead to more deaths soon after an invasive procedure compared with the control arms. The results are similar to previous meta-analyses but identified more studies, more participants and more events which enhanced the precision of the results. They also conducted trial sequential analyses which provide estimates about the reliability of current evidence and prevent premature conclusions from meta-analyses.
The authors concluded, the present meta-analysis based on sufficient evidence demonstrated by trial sequential analysis (TSA) indicates that there is significant reduction in lung cancer mortality between LDCT and other control groups. Moreover, the results of the subgroup analyses indicate that, LDCT screening has shown statistically significant mortality benefits in high quality trials, whereas low-quality trials found no significant difference. It is mandatory to identify lung cancer risk factors among the Asian population and to establish appropriate eligible criteria in the screening program for different races. The benefit of LDCT is expected to be heavily influenced by the risk of lung cancer in the different target group (smoking status, female and Asian) being screened. Due to tenuous balance of benefits and harms, medical decision making is recommended for individuals who are considering LDCT screening. More studies are warranted to optimize the approach to LDCT screening.
Based on review of the peer reviewed medical literature which included randomized controlled trials (RCTs) and systematic reviews and meta-analyses regarding low dose computed tomography (LDCT) screening for lung cancer, findings from two larger trials (NELSON, NLST [National Lung Screening Trial]); total n = 69,276), resulted in pooled data displaying a risk ratio (RR) of 0.80 (95% CI 0.71–0.91). In addition, regardless male or female, LDCT showed a reduction of lung cancer mortality. The NELSON trial is the only fully powered RCT which presented its 10-year mortality findings in 2018 at the International Association for the Study of Lung Cancer (IASCL) 19th World Conference on Lung Cancer (WCLC). Based on the meta-analysis completed in 2019 by Huang et. al., sufficient evidence has been demonstrated by these two trials as there was a significant reduction in lung cancer mortality between LDCT and other control groups. However, further evaluation is required to determine which patients with positive screening results in cancer. The U.S. Preventative Services Task Force (USPSTF) in 2013 found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk individuals can prevent a substantial number of lung cancer related deaths and the magnitude of benefit to the individual depends on that individuals risk for lung cancer because those who are at highest risk are most likely to benefit. The USPSTF concluded with moderate certainty that annual screening for lung cancer with LDCT is of moderate net benefit in asymptomatic individuals who are at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. The moderate net benefit of screening depends on limiting screening to persons who are at high risk, the accuracy of image interpretation being similar to that found in the National Lung Screening Trial (NLST), and the resolution of most false-positive results without invasive procedures. Low dose computed tomography (LDCT) has shown high sensitivity and acceptable specificity for the detection of lung cancer in high-risk individuals, Chest radiography and sputum cytology evaluation has not shown adequate sensitivity or specificity as screening tests. Pooled results comparing LDCT to no screening or chest x-ray (CXR) establish a survival benefit and show an increase in detection of stage I cancers. Therefore, LDCT is currently the only recommended screening test for lung cancer. The evidence is sufficient to determine this technology results in meaningful improvement in the net health outcomes for those individuals at high risk for lung cancer. Therefore, screening for lung cancer with low dose computed tomography (LDCT) annually may be considered medically necessary for high risk patients who meet criteria.
Clinicians may encounter asymptomatic patients who are interested in lung cancer screening but do not meet the criteria of high risk for lung cancer (USPSTF: adults aged 55 to 80 years of age, have a 30 pack-year smoking history, and currently smoke or have quit smoking within past 15 years). The risk for lung cancer increases with age (most commonly in adults aged 55 years and older) and cumulative exposure to tobacco smoke. Current evidence is lacking on the net benefit of expanding low dose computed tomography (LDCT) screening to include lower risk patients as the incidence of lung cancer is relatively low in individuals younger than 55 years of age. Also, the balance of benefits and harms of screening may be unfavorable in these lower risk patients. It is important that individual who are at lower risk for lung cancer be aware of the potential harms of screening (false-negative, false-positive results, incidental findings, overdiagnosis and radiation exposure). Several society guidelines recommend using LDCT for screening high risk group (age 55 to 80 years, pack-year smoking history i.e. 30 pack years and currently smoke or have quit smoking in the past 15 years). Due to the tenuous balance of benefits and harms in this low risk group more studies are warranted to optimize the approach of LDCT screening in these individuals. The evidence is insufficient to determine the effects of this technology on net health outcomes in the low risk population of patients.
December 2013, the USPSTF recommended annual screening for lung cancer with low dose computed tomography (LDCT) in adults aged 55 to 80 years who have a 30 pack year smoking history and currently smoke or have quit within the past 15 years.
Screening should be discontinued once 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 curative lung surgery.
A rating of A and B from the USPSTF applies to the Affordable Care Act (ACA) preventative services. This recommendation is Grade B.
The NCCN Panel recommends lung cancer screening using LDCT for individuals with high risk factors. There are 2 groups of individuals who qualify as high risk:
In 2019, the American Cancer Society (ACS) updated their guideline on lung cancer screening. The guideline recommends yearly lung cancer screening with a low-dose CT scan (LDCT) for certain people at higher risk for lung cancer who meet the following conditions:
In 2018, the American College of Chest Physicians (ACCP) updated their guidelines for screening for lung cancer, which includes the following recommendations:
In 2012, the American Association for the Thoracic Surgery published guidelines for lung cancer screening. The guidelines recommend annual lung cancer screening with low dose computed tomography (LDCT) for the following individuals:
Also, low dose computed tomography lung cancer screening should be offered at 50 to 79 years with a 20 pack year smoking history and additional comorgidity that produces cummulative risk of developing lung cancer of ≥5% in 5 years.
In 2012, the American Lung Association updated their lung cancer screening guidelines for high risk individuals that meet the following criteria:
Note: This policy does not apply to individuals with signs and/or symptoms. In symptomatic individuals, a diagnostic work up appropriate to the clinical presentation should be undertaken, rather than screening.
Patient selection criteria below is based on the U.S. Preventative Services Task Force (USPSTF) B recommendation:
Low-dose computed tomography (LDCT) scanning, no more frequently than annually, may be considered medically necessary as a screening technique for lung cancer in asymptomatic individuals who meet ALL of the following criteria:*
Lung cancer screening using low dose computed tomography (LDCT) would be considered not medically necessary for the following indications:
*This is based on a range of chest or other organ signs, symptoms or conditions which would question the member’s ability to undergo non-surgical treatment if a lung cancer was discovered. For example, congestive heart failure, advanced cancer from another site or a patient with COPD who uses oxygen when ambulating, would be examples of conditions that would “substantially limit life expectancy.”
Low-dose computed tomography (LDCT) is considered investigational as a screening technique for lung cancer when the above criteria is not met and for all other screening indications in asymptomatic individuals.
At this time the evidence is insufficient to show that screening would be beneficial or would outweigh the harms associated with screening for asymptomatic individuals considered at low to moderate risk for lung cancer. The evidence is insufficient to determine the effects on net health outcomes for asymptomatic individuals that do not meet high risk screening criteria above.
A pack-year is a way to measure the amount a person has smoked over a long period of time. It is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked. For example, 1 pack year is equal to smoking 1 pack per day for 1 year, or 2 packs per day for half a year, and so on.
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