Retrospective identification of low-risk individuals eligible for biennial lung cancer screening using PanCan-based and deep learning-based risk thresholds

N. Antonissen, K. Venkadesh, H. Gietema, R. Vliegenthart, Z. Saghir, M. Silva, E. Pastorino, E. Scholten, M. Prokop, C. Schaefer-Prokop and C. Jacobs

Annual Meeting of the European Society of Thoracic Imaging 2023.

Purpose: Current nodule management protocols for managing negative screening results have varying follow-up intervals; LungRADS recommends a 1-year screening interval for all negative screens (category 1/2), while the International Lung Screen Trial (ILST) protocol recommends 1-year interval for participants with indeterminate nodules (PanCan score 1.5% - 6%) and 2-year interval for participants with no or very low risk nodules (PanCan score < 1.5%). In this study, we retrospectively evaluated the use of PanCan and DL-based malignancy thresholds to identify individuals eligible for biennial screening, aiming to reduce screening-related harms and enhancing cost-effectiveness without causing potential delay of cancer diagnosis.

Methods and materials: All baseline CT-scans from the Danish Lung Cancer Screening Trial (DLCST) and Multicentric Italian Lung Detection (MILD) were pooled and linked to a lung cancer diagnosis within 2 years, resulting in 4.157 non-cancer and 53 cancer cases. PanCan1a and DL-based malignancy risk scores were calculated for all screen-annotated nodules. For cases with no screen-annotated nodules, the risk score for participants was set as 0%. For both risk calculators, we used a nodule-risk cut-off of < 1.5% to identify low-risk participants for biennial follow-up, based on the ILST protocol. We computed the number of low-risk participants eligible for biennial screening for all included baseline scans (n=4.210) using the risk dominant nodule per scan and calculated the number of cancer cases in the biennial group.

Results: The DL-based and PanCan-based risk threshold < 1.5% identified 3.729 and 3.720 individuals, respectively, meeting the criteria for biennial screening. This would result in a reduction of 88.6% and 88.4% of the scans in the second screening round, respectively. The group referred for biennial screening included 14 and 16 cancers with DL and PanCan-based risk scores <1.5%, respectively. Most of the cancer cases (n=13), had no nodule annotated at baseline CT, leading to a 0% risk score at baseline. Retrospectively 4 of the 13 cancers were visible in the baseline scan, yet primarily not annotated by the screening radiologist.

Conclusion: Risk threshold-based identification of low-risk subjects for biennial screening largely reduces the number of 1-year follow-up scans. DL and PanCan for risk assessment performed very similarly, indicating the potential of DL for readily available risk assessment of baseline scans. A risk threshold of < 1.5%, as implemented in the ILST protocol, leads to delayed diagnosis of cancers either primarily missed during baseline or developing as interval cancers. More research is needed to study the type of cancers with delayed diagnosis and whether such delay leads to diagnostic stage shift.

Limitations: This study is a retrospective analysis on data from two screening trials, restricted to the baseline round.