Can autoantibody tests enhance lung cancer screening?—an evaluation of EarlyCDT®-Lung in context of the German Lung Cancer Screening Intervention Trial (LUSI)

Abstract

Background: Tumor-associated autoantibodies are considered promising markers for early lung cancer detection; so far, however, their capacity to detect cancer has been tested mostly in a clinical context, but not in population screening settings. This study evaluates the early detection accuracy, in terms of sensitivity and specificity, of EarlyCDT ® -Lung-a test panel of seven tumor-associated autoantibodies optimized for lung cancer detection-using blood samples originally collected as part of the German Lung Cancer Screening Intervention Trial.Methods: The EarlyCDT ® -Lung test was performed for all participants with lung cancer detected via lowdose computed tomography and with available blood samples taken at detection, and for 180 retrospectively selected cancer-free participants at the end of follow-up: 90 randomly selected from among all cancerfree participants (baseline controls) and 90 randomly selected from among cancer-free participants with suspicious imaging findings (suspicious nodules controls). Sensitivity and specificity of lung cancer detection were estimated in the case group and the two control groups, respectively.Results: In the case group, the test panel showed a sensitivity of only 13.0% (95% CI: 4.9-26.3%).Specificity was estimated at 88.9% (95% CI: 80.5-94.5%) in the baseline control group, and 91.1% (95% CI: 83.2-96.1%) among controls presenting CT-detected nodules. Conclusions:The test panel showed insufficient sensitivity for detecting lung cancer at an equally early stage as with low-dose computed tomography screening.

Personalising lung cancer screening: An overview of risk‐stratification opportunities and challenges

“…88,89 However, the average age in these studies and pilots was around 65, at which the life-expectancy is 18-22 years. 90 In these studies, self-selection and physician-selection may have aided in reducing the uptake of screening in individuals with low life-expectancies; but within large-scale programs, the uptake of screening in individuals with limited lifeexpectancies may still be considerable. 91 Consequently, discussions are ongoing on how to explicitly incorporate comorbidities and lifeexpectancy in recommendations and shared decision-making for lung cancer screening.…”

“…Furthermore, analyses from the German Lung Tumour Screening and Intervention study (LUSI), showed that the EarlyCDT-Lung test had a low sensitivity (13%) for early stage, small tumours as detected by CT screening. 90 In order for biomarkers to be applied in lung cancer screening practice, they need to have improved performance over currently validated risk-prediction models, or provide complementary predictive benefit to these models. Furthermore, they need to provide this information in a cost-effective manner.…”

Seven tumor‐associated autoantibodies as a serum biomarker for primary screening of early‐stage non‐small cell lung cancer

“…In addition to patient factors, the performance of different brands of reagents may also be different. In the Gonzalez Maldonado study, 23 the sensitivity of the EarlyCDT ® ‐Lung‐a test panel of 7‐TAAbs was only 13.0%, and the specificity was 88.9%. In our study, although the sensitivity was higher than theirs, it was still at a low level, indicating that the panel of 7‐TAAbs was not sensitive enough in the diagnosis of early LC.…”

Performance of the EarlyCDT® Lung test in detection of lung cancer and pulmonary metastases in a high-risk cohort

“…The EarlyCDT® Lung test has previously been tested in high-risk [20][21][22]. As seen in Table 3, the TAA assay performs best in heavy smokers, patients older than 75 years and late stage disease; sex does not seem to influence outcome.…”

“…Recently, the EarlyCDT® Lung test was evaluated in the context of the German Lung Cancer Screening Trial (LUSI) [22]. Sensitivity was found to be as low as 13 %.…”