Lung cancer screening using low-dose computed tomography assessed by IQWiG in Germany

On behalf of the Federal Joint Committee (G-BA), the Institute for Quality and Efficiency in Health Care (IQWiG) investigated whether (former) heavy smokers within statutory health insurance (SHI) should be offered lung cancer screening using low-dose computed tomography (LDCT).

Lung cancer is the most common cause of cancer-related death in men in Germany and the second most common in women (after breast cancer). In about 9/10 men and at least 6/10 women with lung cancer, the disease is attributed to active smoking. Lung cancer is usually only discovered at a late stage, which results in a low 5-year survival rate: only about 15% in men and 21% in women.

LDCT could be a suitable method for the early detection of lung cancer. With LDCT, changing the various CT parameters, such as tube voltage and current, leads to a reduction in the radiation dose with sufficient image quality for the diagnosis. There is currently no systematic screening for lung cancer in Germany, and LDCT is not part of the scope of the SHI.

The study aimed to evaluate the benefit of screening for lung cancer using LDCT compared to no (or no systematic) screening in people with an increased risk of lung cancer in current or former heavy (tobacco) smokers concerning patient-relevant endpoints.

A systematic literature search was carried out in the databases MEDLINE, Cochrane Database of Systematic Reviews and Health Technology Assessment Database with restriction to the publication period of the last six years. The additional search for primary studies in the databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials was carried out.

As a result, nine relevant randomized controlled studies and two ongoing studies were identified. Furthermore, one completed study with no reported results and four studies with unclear status were identified.

Results – lung cancer-specific mortality:

• The joint evaluation of the studies with moderate and high qualitative reliability of results showed a statistically significant difference (IDR: 0.80; 95% CI [0.69; 0.93]; p = 0.012) in favor of LDCT screening

Results – adverse events (AEs):

• Usable data on AEs were only available in the DANTE trial with moderately qualitative reliability of results for the occurrence of AEs after an operation and for the occurrence of AEs with a severity ≥three after an operation. The results for the most extended observation period since randomization were shown (maximum eight years). The evaluation showed a statistically significant difference in the occurrence of AEs after an operation with an abnormal finding (OR 3.48; 95% CI [1.41; 8.62]; p = 0.004). The further restriction to AEs with a severity ≥3 also showed a statistically significant difference between the two study groups (OR 4.25; 95% CI [0.92; 19.69]; p = 0.046). There was, therefore, an effect to the disadvantage of LDCT screening

Results – consequences of false-positive screening results:

• There were data identified with high-quality results in 3 trials (DLCST, ITALUNG, and NELSON) and with moderate quality results in 3 further trials (DANTE, LUSI, and MILD). Overall, between 0.1% and 1.5% of the participants in the trials experienced a consequence of false-positive results. A total of 3 severe complications and 20 minor complications occurred in patients who underwent surgery with benign findings. Thus, severe or minor complications occurred in 0.04% or 0.3% of all participants invited to the screening. There is, therefore, evidence of harm of lung cancer screening using LDCT compared to no screening regarding the consequences of false-positive screening results

Results – overdiagnoses:

• Overdiagnoses related to the people invited to the screening:
  • Data with high-quality results were available from the three trials (DLCST, ITALUNG, and NELSON) and data with moderate quality results from the other five trials (DANTE, LUSI, MILD, NLST, and LSS). The overdiagnosis risk was highest in the DANTE and DLCST trials with 2.2% and 2.1%. For the LUSI, MILD, and NELSON trials, the calculated risk of overdiagnosis for study participants was 0.9%, 0.6%, and 0.6%. An overdiagnosis risk of 1.2% and 0.1% was calculated in the two trials (LSS and NLST) for comparison of LDCT screening versus chest x-ray screening
• Overdiagnoses related to those diagnosed with lung cancer during the screening phase:
  • Data from 5 trials were available, including four trials for comparison against no screening (DLCST, ITALUNG, LUSI, and NELSON). The result of the DLCST trial was particularly noticeable since an overdiagnosis risk of 63.2% was calculated. For the LUSI and NELSON trials, the overdiagnosis risk was 28.6% and 16.2%. No overdiagnoses were found in the ITALUNG study. An overdiagnosis risk of 2.8% was calculated for the NLST study comparing chest x-ray screening
• Therefore, there is thus evidence of harm in lung cancer screening using LDCT compared to no screening regarding overdiagnosis, i.e., resulting from the invasive diagnosis and treatment, including the associated complications and side effects.

There was no statistically significant difference found in the studies' results regarding all-cause mortality. Data on health-related quality of life were not available in the studies or could not be used for the benefit assessment.

The IQWiG summarized that there is an indication of the benefits of LDCT screening compared to no screening, and thus that the benefit of LDCT lung cancer screening outweighs the harm for (former) heavy smokers.

Comments on the published preliminary report will be viewed after the deadline (04.08.2020). If they leave questions unanswered, the respondents will be invited to an oral discussion. The IQWiG will then prepare the final report.

The preliminary report in German can be found here.

Subscribe to our newsletter delivered every second week not to miss important reimbursement information.