BACKGROUND: Current guidelines for lung cancer screening via low-dose computed tomography recommend annual screening for all candidates meeting basic eligibility criteria. However, lung cancer risk of eligible screening participants can vary widely, and further risk stratification could be used to individually optimize screening intervals in view of expected benefits, possible harms and financial costs. To this effect, models have been developed in the US National Lung Screening Trial based on self-reported lung cancer risk factors and imaging data. We evaluated these models using data from an independent screening trial in Germany. METHODS: We examined the Polynomial model by Schreuder et al., the Lung Cancer Risk Assessment Tool extended by CT characteristics (LCRAT + CT) by Robbins et al., and a criterion of presence vs. absence of pulmonary nodules ≥4 mm (Patz et al.), applied to sub-sets of screening participants according to eligibility criteria. Discrimination was evaluated via the receiver operating characteristic curve. Delayed diagnoses and false positive results were calculated at various thresholds of predicted risk. Model calibration was assessed by comparing mean predicted risk versus observed incidence. RESULTS: One thousand five hundred and six participants were eligible for the validation of the LCRAT + CT model, and 1,889 for the validation of the Polynomial model and Patz criterion, yielding areas under the receiver operating characteristic curve of 0.73 (95% CI: 0.63, 0.82), 0.75 (0.67, 0.83), and 0.56 (0.53, 0.72) respectively. Skipping 50% annual screenings (participants within the 5 lowest risk deciles by LCRAT + CT in any round or by the Polynomial model; baseline screening round), would have avoided 75% (21.9%, 98.7%) and 40% (21.8%, 61.1%) false positive screen tests and delayed 10% (1.8%, 33.1%) or no (0%, 32.1%) diagnoses, respectively. Using the Patz criterion, referring 63.2% (61.0% to 65.4%) of participants to biennial screening would have avoided 4% (0.2% to 22.3%) of false positive screen tests but delayed 55% (24.6% to 81.9%) diagnoses. CONCLUSIONS: In this German trial, the LCRAT + CT and Polynomial models showed useful discrimination of screening participants for one-year lung cancer risk following CT examination. Our results illustrate the remaining heterogeneity in risk within screening-eligible subjects and the trade-off between a low-frequency screening approach and delayed detection.
- González Maldonado, S.
- Hynes, L. C.
- Motsch, E.
- Heussel, C. P.
- Kauczor, H. U.
- Robbins, H. A.
- Delorme, S.
- Kaaks, R.
Keywords
- Lung cancer screening
- risk prediction
- screening intervals
- validation
- (available at http://dx.doi.org/10.21037/tlcr-20-1173). Dr. Kauczor reports grants
- from Siemens, grants and personal fees from Philips, personal fees from Boehringer
- Ingelheim, personal fees from Merck Sharp Dohme, personal fees from Astra Zeneca,
- outside the submitted work. Dr. Heussel reports personal fees from Schering-Plough
- 2009-2010, personal fees from Pfizer 2008-2014, personal fees from Basilea 2008,
- 2009, 2010, personal fees from Boehringer Ingelheim 2010, 2014, personal fees from
- Novartis 2010, 2012, 2014, personal fees from Roche 2010, personal fees from
- Astellas 2011, 2012, personal fees from Gilead 2011-2015, personal fees from MSD
- 2011-2013, personal fees from Lilly 2011, personal fees from Intermune 2013-2014,
- personal fees from Fresenius 2013,2014, grants from Siemens 2012-2014, grants from
- Pfizer 2012-2014, grants from MeVis 2012, 2013, grants from Boehringer Ingelheim
- 2014, grants from German Center for Lung Research 2011ff, personal fees from Gilead
- 2008-2014, personal fees from Essex 2008, 2009, 2010, personal fees from
- Schering-Plough 2008, 2009, 2010, personal fees from AstraZeneca 2008-2012, personal
- fees from Lilly 2008, 2009, 2012, personal fees from Roche 2008, 2009, personal fees
- from MSD 2009-2014, personal fees from Pfizer 2010-2014, personal fees from Bracco
- 2010, 2011, personal fees from MEDA Pharma 2011, personal fees from Intermune
- 2011-2014, personal fees from Chiesi 2012, personal fees from Siemens 2012, personal
- fees from Covidien 2012, personal fees from Pierre Fabre 2012, personal fees from
- Boehringer Ingelheim 2012, 2013, personal fees from Grifols 2012, personal fees from
- Novartis 2013-2016, personal fees from Basilea 2015, 2016, personal fees from Bayer
- 2016, outside the submitted work
- In addition, Dr. Heussel has a patent Method and
- Device For Representing the Microstructure of the Lungs. IPC8 Class: AA61B5055FI,
- PAN: 20080208038, Inventors: W Schreiber, U Wolf, AW Scholz, CP Heussel and Stock
- ownership in medical industry: GSK Comitee membership: Chest working group of the
- German Roentgen society National guidelines: bronchial carcinoma, mesothelioma,
- COPD, screening for bronchial carcinoma, CT and MR imaging of the chest, Pneumonia,
- Faculty member of European Society of Thoracic Radiology (ESTI), European
- Respiratory Society (ERS), and member in EIBALL (European Imaging Biomarkers
- Alliance), Tobacco Industry: No relation. The other authors have no conflicts of
- interest to declare.
