A systematic review and meta-analysis of lung cancer risk prediction models
DOI:
https://doi.org/10.2340/1651-226X.2025.42529Keywords:
Lung cancer, risk prediction model, screening, early detection, reviewAbstract
Background: Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Early detection through targeted screening significantly improves patient outcomes. However, identifying high-risk individuals remains a critical challenge.
Purpose: This systematic review evaluates externally validated LC risk prediction models to assess their performance and potential applicability in screening strategies.
Methods: Of the 11,805 initial studies, 66 met inclusion criteria and 38 published mainly between 2020 and 2024 were included in the final analysis. Model methodologies, validation approaches, and performance metrics were extracted and compared.
Results: The review identified 18 models utilising conventional machine learning, six employing neural networks, and 14 comparing different predictive frameworks. The Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCOm2012) demonstrated superior sensitivity across diverse populations, while newer models, such as Optimized Early Warning model for Lung cancer risk (OWL) and CanPredict, showed promising results. However, differences in population demographics and healthcare systems may limit the generalisability of these models.
Interpretation: While LC risk prediction models have advanced, their applicability to specific healthcare systems, such as Finland’s, requires further adaptation and validation. Future research should focus on optimising these models for local contexts to improve clinical impact and cost-effectiveness in targeted screening programmes.
Systematic review registration: PROSPERO CRD42022321391.
Downloads
References
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.
https://doi.org/10.3322/caac.21660 DOI: https://doi.org/10.3322/caac.21660
Tichanek F, Försti A, Hemminki O, Hemminki A, Hemminki K. Survival in lung cancer in the Nordic countries through a half century. Clin Epidemiol. 2023;15:503–10.
https://doi.org/10.2147/CLEP.S406606 DOI: https://doi.org/10.2147/CLEP.S406606
De Koning HJ, Van Der Aalst CM, De Jong PA, Scholten ET, Nackaerts K, Heuvelmans MA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med. 2020;382(6):503–13.
https://doi.org/10.1056/NEJMoa1911793 DOI: https://doi.org/10.1056/NEJMoa1911793
Field JK, Chen Y, Marcus MW, Mcronald FE, Raji OY, Duffy SW. The contribution of risk prediction models to early detection of lung cancer. J Surg Oncol. 2013;108(5):304–11.
https://doi.org/10.1002/jso.23384 DOI: https://doi.org/10.1002/jso.23384
Gray EP, Teare MD, Stevens J, Archer R. Risk prediction models for lung cancer: a systematic review. Clin Lung Cancer. 2016;17(2):95–106.
https://doi.org/10.1016/j.cllc.2015.11.007 DOI: https://doi.org/10.1016/j.cllc.2015.11.007
Schmidt-Hansen M, Berendse S, Hamilton W, Baldwin DR. Lung cancer in symptomatic patients presenting in primary care: a systematic review of risk prediction tools. Br J Gen Pract. 2017;67(659):e396–404.
https://doi.org/10.3399/bjgp17X690917 DOI: https://doi.org/10.3399/bjgp17X690917
Tang W, Peng Q, Lyu Y, Feng X, Li X, Wei L, et al. Risk prediction models for lung cancer: perspectives and dissemination. Chin J Cancer Res. 2019;31(2):316–28.
https://doi.org/10.21147/j.issn.1000-9604.2019.02.06 DOI: https://doi.org/10.21147/j.issn.1000-9604.2019.02.06
Wu Z, Wang F, Cao W, Qin C, Dong X, Yang Z, et al. Lung cancer risk prediction models based on pulmonary nodules: a systematic review. Thorac Cancer. 2022;13(5):664–77.
https://doi.org/10.1111/1759-7714.14333 DOI: https://doi.org/10.1111/1759-7714.14333
Toumazis I, Bastani M, Han SS, Plevritis SK. Risk-based lung cancer screening: a systematic review. Lung Cancer. 2020;147:154–86.
https://doi.org/10.1016/j.lungcan.2020.07.007 DOI: https://doi.org/10.1016/j.lungcan.2020.07.007
Maddison P, Lipka AF, Gozzard P, Sadalage G, Ambrose PA, Lang B, et al. Lung cancer prediction in Lambert-Eaton myasthenic syndrome in a prospective cohort. Sci Rep. 2020;10(1):10546.
https://doi.org/10.1038/s41598-020-67571-9 DOI: https://doi.org/10.1038/s41598-020-67571-9
Liao W, Coupland CAC, Burchardt J, Baldwin DR, Gleeson FV, Hippisley-Cox J, et al. Predicting the future risk of lung cancer: development, and internal and external validation of the CanPredict (lung) model in 19·67 million people and evaluation of model performance against seven other risk prediction models. Lancet Respir Med. 2023;11(8):685–97.
https://doi.org/10.1016/S2213-2600(23)00050-4 DOI: https://doi.org/10.1016/S2213-2600(23)00050-4
Ma Z, Lv J, Zhu M, Yu C, Ma H, Jin G, et al. Lung cancer risk score for ever and never smokers in China. Cancer Commun. 2023;43(8):
877–95.
https://doi.org/10.1002/cac2.12463 DOI: https://doi.org/10.1002/cac2.12463
Wang F, Tan F, Shen S, Wu Z, Cao W, Yu Y, et al. Risk-stratified approach for never- and ever-smokers in lung cancer screening: a prospective cohort study in China. Am J Respir Crit Care Med. 2023;207(1):77–88.
https://doi.org/10.1164/rccm.202204-0727OC DOI: https://doi.org/10.1164/rccm.202204-0727OC
Lee HA, Chao LR, Hsu CY. A 10-year probability deep neural network prediction model for lung cancer. Cancers. 2021;13(4):928.
https://doi.org/10.3390/cancers13040928 DOI: https://doi.org/10.3390/cancers13040928
Lu MT, Raghu VK, Mayrhofer T, Aerts HJWL, Hoffmann U. Deep learning using chest radiographs to identify high-risk smokers for lung cancer screening computed tomography: development and validation of a prediction model. Ann Intern Med. 2020;173(9):704–13.
https://doi.org/10.7326/M20-1868 DOI: https://doi.org/10.7326/M20-1868
Cheng Y, Jiang T, Zhu M, Li Z, Zhang J, Wang Y, et al. Risk assessment models for genetic risk predictors of lung cancer using two-stage replication for Asian and European populations. Oncotarget. 2017;8(33):53959–67.
https://doi.org/10.18632/oncotarget.10403 DOI: https://doi.org/10.18632/oncotarget.10403
Titulaer MJ, Maddison P, Sont JK, Wirtz PW, Hilton-Jones D, Klooster R, et al. Clinical Dutch-English Lambert-Eaton Myasthenic Syndrome (LEMS) Tumor Association Prediction Score accurately predicts small-cell lung cancer in the LEMS. J Clin Oncol. 2011;29(7):902–8.
https://doi.org/10.1200/JCO.2010.32.0440 DOI: https://doi.org/10.1200/JCO.2010.32.0440
Hung RJ, Warkentin MT, Brhane Y, Chatterjee N, Christiani DC, Landi MT, et al. Assessing lung cancer absolute risk trajectory based on a polygenic risk model. Cancer Res. 2021;81(6):1607–15.
https://doi.org/10.1158/0008-5472.CAN-20-1237 DOI: https://doi.org/10.1158/0008-5472.CAN-20-1237
Van ’T Klooster CC, Ridker PM, Cook NR, Aerts JGJV, Westerink J, Asselbergs FW, et al. Prediction of lifetime and 10-year risk of cancer in individual patients with established cardiovascular disease. JACC CardioOncol. 2020;2(3):400–10.
https://doi.org/10.1016/j.jaccao.2020.07.001 DOI: https://doi.org/10.1016/j.jaccao.2020.07.001
Pan Z, Zhang R, Shen S, Lin Y, Zhang L, Wang X, et al. OWL: an optimized and independently validated machine learning prediction model for lung cancer screening based on the UK Biobank, PLCO, and NLST populations. eBioMedicine. 2023;88:104443.
https://doi.org/10.1016/j.ebiom.2023.104443 DOI: https://doi.org/10.1016/j.ebiom.2023.104443
Yeh MCH, Wang YH, Yang HC, Bai KJ, Wang HH, Li YCJ. Artificial intelligence–based prediction of lung cancer risk using nonimaging electronic medical records: deep learning approach. J Med Internet Res. 2021;23(8):e26256.
https://doi.org/10.2196/26256 DOI: https://doi.org/10.2196/26256
Raghu VK, Walia AS, Zinzuwadia AN, Goiffon RJ, Shepard JAO, Aerts HJWL, et al. Validation of a deep learning–based model to predict lung cancer risk using chest radiographs and electronic medical record data. JAMA Netw Open. 2022;5(12):e2248793.
https://doi.org/10.1001/jamanetworkopen.2022.48793 DOI: https://doi.org/10.1001/jamanetworkopen.2022.48793
Chen HY, Wang HM, Lin CH, Yang R, Lee CC. Lung cancer prediction using electronic claims records: a transformer-based approach. IEEE J Biomed Health Inform. 2023;27(12):6062–73.
https://doi.org/10.1109/JBHI.2023.3324191 DOI: https://doi.org/10.1109/JBHI.2023.3324191
Lee JH, Lee D, Lu MT, Raghu VK, Park CM, Goo JM, et al. Deep learning to optimize candidate selection for lung cancer CT screening: advancing the 2021 USPSTF recommendations. Radiology. 2022;305(1):209–18.
https://doi.org/10.1148/radiol.212877 DOI: https://doi.org/10.1148/radiol.212877
Park B, Kim Y, Lee J, Lee N, Jang SH. Risk-based prediction model for selecting eligible population for lung cancer screening among ever smokers in Korea. Transl Lung Cancer Res. 2021;10(12):4390–402.
https://doi.org/10.21037/tlcr-21-566 DOI: https://doi.org/10.21037/tlcr-21-566
Chien LH, Chen CH, Chen TY, Chang GC, Tsai YH, Hsiao CF, et al. Predicting lung cancer occurrence in never-smoking females in Asia: TNSF-SQ, a prediction model. Cancer Epidemiol Biomarkers Prev. 2020;29(2):452–9.
https://doi.org/10.1158/1055-9965.EPI-19-1221 DOI: https://doi.org/10.1158/1055-9965.EPI-19-1221
Charvat H, Sasazuki S, Shimazu T, Budhathoki S, Inoue M, Iwasaki M, et al. Development of a risk prediction model for lung cancer: The Japan Public Health Center‐based Prospective Study. Cancer Sci. 2018;109(3):854–62.
https://doi.org/10.1111/cas.13509 DOI: https://doi.org/10.1111/cas.13509
Jacobsen KK, Kobylecki CJ, Skov-Jeppesen SM, Bojesen SE. Development and validation of a simple general population lung cancer risk model including AHRR-methylation. Lung Cancer. 2023;181:107229.
https://doi.org/10.1016/j.lungcan.2023.107229 DOI: https://doi.org/10.1016/j.lungcan.2023.107229
Jantzen R, Ezer N, Camilleri-Broët S, Tammemägi MC, Broët P. Evaluation of the accuracy of the PLCO m2012 6-year lung cancer risk prediction model among smokers in the CARTaGENE population-based cohort. CMAJ Open. 2023;11(2):E314–22.
https://doi.org/10.9778/cmajo.20210335 DOI: https://doi.org/10.9778/cmajo.20210335
Chandran U, Reps J, Yang R, Vachani A, Maldonado F, Kalsekar I. Machine learning and real-world data to predict lung cancer risk in routine care. Cancer Epidemiol Biomarkers Prev. 2023;32(3):337–43.
https://doi.org/10.1158/1055-9965.EPI-22-0873 DOI: https://doi.org/10.1158/1055-9965.EPI-22-0873
Feng X, Wu WYY, Onwuka JU, Haider Z, Alcala K, Smith-Byrne K, et al. Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools. JNCI J Natl Cancer Inst. 2023;115(9):1050–9.
https://doi.org/10.1093/jnci/djad071 DOI: https://doi.org/10.1093/jnci/djad071
Jacobsen KK, Schnohr P, Jensen GB, Bojesen SE. AHRR (cg05575921) methylation safely improves specificity of lung cancer screening eligibility criteria: a cohort study. Cancer Epidemiol Biomarkers Prev. 2022;31(4):758–65.
https://doi.org/10.1158/1055-9965.EPI-21-1059 DOI: https://doi.org/10.1158/1055-9965.EPI-21-1059
Robbins HA, Alcala K, Swerdlow AJ, Schoemaker MJ, x Wareham N, Travis RC, et al. Comparative performance of lung cancer risk models to define lung screening eligibility in the United Kingdom. Br J Cancer. 2021;124(12):2026–34.
https://doi.org/10.1038/s41416-021-01278-0 DOI: https://doi.org/10.1038/s41416-021-01278-0
Bhardwaj M, Schöttker B, Holleczek B, Brenner H. Comparison of discrimination performance of 11 lung cancer risk models for predicting lung cancer in a prospective cohort of screening-age adults from Germany followed over 17 years. Lung Cancer. 2022;174:83–90.
https://doi.org/10.1016/j.lungcan.2022.10.011 DOI: https://doi.org/10.1016/j.lungcan.2022.10.011
Ostrowski M, Bińczyk F, Marjański T, Dziedzic R, Pisiak S, Małgorzewicz S, et al. Performance of various risk prediction models in a large lung cancer screening cohort in Gdańsk, Poland – a comparative study. Transl Lung Cancer Res. 2021;10(2):1083–90.
https://doi.org/10.21037/tlcr-20-753 DOI: https://doi.org/10.21037/tlcr-20-753
Pasquinelli MM, Tammemägi MC, Kovitz KL, Durham ML, Deliu Z, Rygalski K, et al. Brief report: risk prediction model versus united states preventive services task force 2020 draft lung cancer screening eligibility criteria – reducing race disparities. JTO Clin Res Rep. 2021;2(3):100137.
https://doi.org/10.1016/j.jtocrr.2020.100137 DOI: https://doi.org/10.1016/j.jtocrr.2020.100137
Pu CY, Lusk CM, Neslund-Dudas C, Gadgeel S, Soubani AO, Schwartz AG. Comparison between the 2021 USPSTF lung cancer screening criteria and other lung cancer screening criteria for racial disparity in eligibility. JAMA Oncol. 2022;8(3):374.
https://doi.org/10.1001/jamaoncol.2021.6720 DOI: https://doi.org/10.1001/jamaoncol.2021.6720
Walter J, Kauffmann‐Guerrero D, Muley T, Reck M, Fuge J, Günther A, et al. Comparison of the sensitivity of different criteria to select lung cancer patients for screening in a cohort of German patients. Cancer Med. 2023;12(7):8880–96.
https://doi.org/10.1002/cam4.5638 DOI: https://doi.org/10.1002/cam4.5638
Williams RM, Kareff SA, Sackstein P, Roy T, Luta G, Kim C, et al. Race & sex disparities related to low-dose computed tomography lung cancer screening eligibility criteria:a lung cancer cases review. Lung Cancer. 2022;169:55–60.
https://doi.org/10.1016/j.lungcan.2022.05.008 DOI: https://doi.org/10.1016/j.lungcan.2022.05.008
Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. Thorax. 2021;76(2):161–8.
https://doi.org/10.1136/thoraxjnl-2020-215158 DOI: https://doi.org/10.1136/thoraxjnl-2020-215158
Callender T, Imrie F, Cebere B, Pashayan N, Navani N, Van Der Schaar M, et al. Assessing eligibility for lung cancer screening using parsimonious ensemble machine learning models: a development and validation study. PLoS Med. 2023;20(10):e1004287.
https://doi.org/10.1371/journal.pmed.1004287 DOI: https://doi.org/10.1371/journal.pmed.1004287
Lebrett MB, Balata H, Evison M, Colligan D, Duerden R, Elton P, et al. Analysis of lung cancer risk model (PLCO M2012 and LLP v2) performance in a community-based lung cancer screening programme. Thorax. 2020;75(8):661–8.
https://doi.org/10.1136/thoraxjnl-2020-214626 DOI: https://doi.org/10.1136/thoraxjnl-2020-214626
Kojo K, Turtiainen T, Holmgren O, Kurttio P. Radon exposure concentrations in finnish workplaces. Health Phys. 2023;125(2):92–101.
https://doi.org/10.1097/HP.0000000000001692 DOI: https://doi.org/10.1097/HP.0000000000001692
Pitkäniemi J, Heikkinen S, Seppä K, Ryynänen H, Ylöstalo T, Eriksson JG, et al. Pooling of Finnish population-based health studies: lifestyle risk factors of colorectal and lung cancer. Acta Oncol. 2020;59(11):1338–42.
https://doi.org/10.1080/0284186X.2020.1789214 DOI: https://doi.org/10.1080/0284186X.2020.1789214
Andersén H, Aro M, Kaarteenaho R, Koivunen J, Mäyränpää MI, Sihvo E, et al. Lung cancer in Finland. J Thorac Oncol. 2024;19(9):1265–71.
https://doi.org/10.1016/j.jtho.2024.06.005 DOI: https://doi.org/10.1016/j.jtho.2024.06.005
Usher-Smith JA, Sharp SJ, Luben R, Griffin SJ. Development and validation of lifestyle-based models to predict incidence of the most common potentially preventable cancers. Cancer Epidemiol Biomarkers Prev. 2019;28(1):67–75.
https://doi.org/10.1158/1055-9965.EPI-18-0400 DOI: https://doi.org/10.1158/1055-9965.EPI-18-0400
O’Dowd EL, Ten Haaf K, Kaur J, Duffy SW, Hamilton W, Hubbard RB, et al. Selection of eligible participants for screening for lung cancer using primary care data. Thorax. 2022;77(9):882–90.
https://doi.org/10.1136/thoraxjnl-2021-217142 DOI: https://doi.org/10.1136/thoraxjnl-2021-217142
Kats DJ, Adie Y, Tlimat A, Greco PJ, Kaelber DC, Tarabichi Y. Assessing different approaches to leveraging historical smoking exposure data to better select lung cancer screening candidates: a retrospective validation study. Nicotine Tob Res. 2021;23(8):1334–40.
https://doi.org/10.1093/ntr/ntaa192 DOI: https://doi.org/10.1093/ntr/ntaa192
Smith RJ, Vijayaharan T, Linehan V, Sun Z, Ein Yong JH, Harris S, et al. Efficacy of risk prediction models and thresholds to select patients for lung cancer screening. Can Assoc Radiol J. 2022;73(4):672–9.
https://doi.org/10.1177/08465371221089899 DOI: https://doi.org/10.1177/08465371221089899
Nguyen OTD, Fotopoulos I, Markaki M, Tsamardinos I, Lagani V, Røe OD. Improving lung cancer screening selection: The HUNT lung cancer risk model for ever-smokers versus the NELSON and 2021 United States Preventive Services Task Force criteria in the cohort of Norway: a population-based prospective study. JTO Clin Res Rep. 2024;5(4):100660.
https://doi.org/10.1016/j.jtocrr.2024.100660 DOI: https://doi.org/10.1016/j.jtocrr.2024.100660
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2025 Ghida Khalife, Matilda Nilsson, Lotta Peltola, Juho Waris, Antti Jekunen, Riikka-Leena Leskelä, Heidi Andersén, Mikko Nuutinen , Eija Heikkilä, Susanna Nurmi-Rantala, Paulus Torkki

This work is licensed under a Creative Commons Attribution 4.0 International License.
