Lung cancer over- and under-screening_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CAO Hang ^1,2,3 , ZHANG Yang ^1,2,3 ,  CHEN Haiquan ^1,2,3

1. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, State Key Laboratory of Genetic Complexity and Developmental Biology, Shanghai, 200032, P. R. China;
2. Institute of Thoracic Oncology, Fudan University, Shanghai, 200032, P. R. China;
3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, P. R. China;

Corresponding?author：

CHEN Haiquan, Email: hqchen1@yahoo.com

Keywords：

Lung cancer; screening; over-screening; under-screening; ground-glass opacity; tumor biology; low-age, low-frequency screening strategy; individualized risk

DOI：

10.7507/1007-4848.202607051

Video：

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Abstract Full text Figures/Tables Video References Cited by

Lung cancer screening is currently challenged by the dual dilemma of over-screening and under-screening. Over-screening is primarily manifested by low-dose computed tomography (LDCT) performed at frequencies exceeding clinical necessity, as well as overly intensive short-interval follow-up of indolent or clinically insignificant lesions, resulting in cumulative radiation exposure, patient anxiety, and waste of healthcare resources. Under-screening, in contrast, is reflected in the failure of high-risk populations to receive recommended LDCT screening, insufficient coverage of individuals with emerging non-traditional risk factors by current guidelines, and delayed identification or management of aggressive early-stage lesions, ultimately leading to late-stage diagnosis and substantial physical, psychological, and financial burdens on patients. Resolving this paradox requires a screening strategy deeply aligned with the biological heterogeneity of lung cancer. Available evidence suggests that lung cancer generally follows three evolutionary trajectories: occult primary tumors with early systemic metastasis, rapidly emerging and progressing solid nodules, and a slowly progressing course characterized by ground-glass opacity (GGO). GGO-type lung cancer may remain clinically indolent for a considerable period, but may ultimately transform into lethal invasive disease. Approximately 95% of persistent, slowly progressing GGOs harbor malignant pathology; nevertheless, to avoid overtreatment of stable lesions, intervention should be strictly reserved for lesions demonstrating radiological progression or continuous enlargement. This article proposes an exploratory "low-age, low-frequency" screening strategy aimed at harmonizing screening intervals with tumor biology and individualized risk. By emphasizing the capture of the "curative time window" and timely intervention for persistently progressing lesions, this strategy seeks to reduce the global burden of advanced lung cancer while maximizing curative benefit and cost-effectiveness.

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1. Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025[J]. CA Cancer J Clin, 2025, 75(1): 10-45.
2. Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Cent, 2024, 4(1): 47-53.
3. Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening[J]. N Engl J Med, 2011, 365(5): 395-409.
4. Bonney A, Malouf R, Marchal C, et al. Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality[J/OL]. Cochrane Database Syst Rev, 2022, 8(8): CD013829. DOI: 10.1002/14651858.CD013829.pub2.
5. Sadate A, Occean BV, Beregi JP, et al. Systematic review and meta-analysis on the impact of lung cancer screening by low-dose computed tomography[J]. Eur J Cancer, 2020, 134: 107-114.
6. Cao H, Zhang Y, Fu F, et al. Over- and underscreening for lung cancer[J]. Transl Lung Cancer Res, 2026, 15(6): 185.
7. Church TR, Black WC, Aberle DR, et al. Results of initial low-dose computed tomographic screening for lung cancer[J]. N Engl J Med, 2013, 368(21): 1980-1991.
8. de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial[J]. N Engl J Med, 2020, 382(6): 503-513.
9. Chang GC, Chiu CH, Yu CJ, et al. Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study[J]. Lancet Respir Med, 2024, 12(2): 141-152.
10. Luo X, Zheng S, Liu Q, et al. Should nonsmokers be excluded from early lung cancer screening with low-dose spiral computed tomography? Community-based practice in Shanghai[J]. Transl Oncol, 2017, 10(4): 485-490.
11. Zhang Y, Jheon S, Li H, et al. Results of low-dose computed tomography as a regular health examination among Chinese hospital employees[J]. J Thorac Cardiovasc Surg, 2020, 160(3): 824-831.
12. Kim YW, Joo DH, Kim SY, et al. Gender disparities and lung cancer screening outcomes among individuals who have never smoked[J/OL]. JAMA Netw Open, 2025, 8(1): e2454057. DOI: 10.1001/jamanetworkopen.2024.54057.
13. Kang HR, Cho JY, Lee SH, et al. Role of low-dose computerized tomography in lung cancer screening among never-smokers[J]. J Thorac Oncol, 2019, 14(3): 436-444.
14. Wang J, Cao H, He N, et al. Evolving trends in surgically managed lung cancer: a 16-year hospital-based epidemiological analysis[J/OL]. Lung Cancer, 2025, 208: 108754. DOI: 10.1016/j.lungcan.2025.108754.
15. Ye T, Deng L, Wang S, et al. Lung adenocarcinomas manifesting as radiological part-solid nodules define a special clinical subtype[J]. J Thorac Oncol, 2019, 14(4): 617-627.
16. Fu F, Zhang Y, Wen Z, et al. Distinct prognostic factors in patients with stageⅠnon-small cell lung cancer with radiologic part-solid or solid lesions[J]. J Thorac Oncol, 2019, 14(12): 2133-2142.
17. Fu F, Shang J, Yan Y, et al. Genomic and transcriptomic dynamics in the stepwise progression of lung adenocarcinoma[J/OL]. Cell Res, 2025, 35(12): 1037-1055. DOI: 10.1038/s41422-025-01119-8.
18. Kakinuma R, Noguchi M, Ashizawa K, et al. Natural history of pulmonary subsolid nodules: a prospective multicenter study[J]. J Thorac Oncol, 2016, 11(7): 1012-1028.
19. Ye T, Deng L, Xiang J, et al. Predictors of pathologic tumor invasion and prognosis for ground glass opacity featured lung adenocarcinoma[J]. Ann Thorac Surg, 2018, 106(6): 1682-1690.
20. Ebell M, Herzstein J. Improving quality by doing less: overscreening[J]. Am Fam Physician, 2015, 91(1): 22-24.
21. Li N, Tan F, Chen W, et al. One-off low-dose CT for lung cancer screening in China: a multicentre, population-based, prospective cohort study[J]. Lancet Respir Med, 2022, 10(4): 378-391.
22. Zhang Y, Chen H. Lung cancer screening: who pays? who receives?-the Chinese perspective[J]. Transl Lung Cancer Res, 2021, 10(5): 2389-2394.
23. Wei MN, Su Z, Wang JN, et al. Performance of lung cancer screening with low-dose CT in Gejiu, Yunnan: a population-based, screening cohort study[J]. Thorac Cancer, 2020, 11(5): 1224-1232.
24. Chang B, Hwang JH, Choi YH, et al. Natural history of pure ground-glass opacity lung nodules detected by low-dose CT scan[J]. Chest, 2013, 143(1): 172-178.
25. Song YS, Park CM, Park SJ, et al. Volume and mass doubling times of persistent pulmonary subsolid nodules detected in patients without known malignancy[J]. Radiology, 2014, 273(1): 276-284.
26. Lee SW, Leem CS, Kim TJ, et al. The long-term course of ground-glass opacities detected on thin-section computed tomography[J]. Respir Med, 2013, 107(6): 904-910.
27. Guo R, Zhang Y, Ma Z, et al. Overuse of follow-up chest computed tomography in patients with incidentally identified nodules suspicious for lung cancer[J]. J Cancer Res Clin Oncol, 2022, 148(5): 1147-1152.
28. Liu M, Li M, Zheng R, et al. Comparison of 10-year survival outcomes between CT surveillance and surgery for ground-glass nodules[J/OL]. Radiology, 2025, 317(1): e250366. DOI: 10.1148/radiol.250366.
29. Wu H, Fu F, Ye T, et al. Active surveillance of multifocal ground-glass opacities: results of a prospective multicenter trial (ECTOP1021)[J]. J Thorac Oncol, 2026, 21(1): 150-159.
30. Mase VJ Jr, Detterbeck FC. Approach to the subsolid nodule[J]. Clin Chest Med, 2020, 41(1): 99-113.
31. Pastorino U, Sverzellati N, Sestini S, et al. Ten-year results of the multicentric Italian lung detection trial demonstrate the safety and efficacy of biennial lung cancer screening[J]. Eur J Cancer, 2019, 118: 142-148.
32. Robbins HA, Berg CD, Cheung LC, et al. Identification of candidates for longer lung cancer screening intervals following a negative low-dose computed tomography result[J]. J Natl Cancer Inst, 2019, 111(9): 996-999.
33. Archer JM, Mendoza DP, Hung YP, et al. Surgical resection of benign nodules in lung cancer screening: incidence and features[J/OL]. JTO Clin Res Rep, 2023, 4(12): 100605. DOI: 10.1016/j.jtocrr.2023.100605.
34. Grogan EL, Weinstein JJ, Deppen SA, et al. Thoracic operations for pulmonary nodules are frequently not futile in patients with benign disease[J]. J Thorac Oncol, 2011, 6(10): 1720-1725.
35. Gao W, Wen CP, Wu A, et al. Association of computed tomographic screening promotion with lung cancer overdiagnosis among Asian women[J]. JAMA Intern Med, 2022, 182(3): 283-290.
36. Wang M, Lin S, He N, et al. The introduction of low-dose CT imaging and lung cancer overdiagnosis in Chinese women[J]. Chest, 2023, 163(1): 239-250.
37. Kakinuma R, Muramatsu Y, Asamura H, et al. Low-dose CT lung cancer screening in never-smokers and smokers: results of an eight-year observational study[J]. Transl Lung Cancer Res, 2020, 9(1): 10-22.
38. Tang Y, Zhou L, Wang F, et al. Assessing the efficiency of eligibility criteria for low-dose computed tomography lung screening in China according to current guidelines[J/OL]. BMC Med, 2024, 22(1): 267. DOI: 10.1186/s12916-024-03507-8.
39. Triphuridet N, Zhang SS, Nagasaka M, et al. Low-dose computed tomography (LDCT) lung cancer screening in Asian female never-smokers is as efficacious in detecting lung cancer as in Asian male ever-smokers: a systematic review and meta-analysis[J]. J Thorac Oncol, 2023, 18(6): 698-717.
40. Pelosof L, Ahn C, Gao A, et al. Proportion of never-smoker non-small cell lung cancer patients at three diverse institutions[J/OL]. J Natl Cancer Inst, 2017, 109(7): djw295. DOI: 10.1093/jnci/djw295.
41. Rissanen E, Heikkinen S, Seppa K, et al. Incidence trends and risk factors of lung cancer in never smokers: pooled analyses of seven cohorts[J]. Int J Cancer, 2021, 149(12): 2010-2019.
42. Osarogiagbon RU, Liao W, Faris NR, et al. Lung cancer diagnosed through screening, lung nodule, and neither program: a prospective observational study of the detecting early lung cancer (DELUGE) in the Mississippi Delta cohort[J]. J Clin Oncol, 2022, 40(19): 2094-2105.
43. Zeng H, Ran X, An L, et al. Disparities in stage at diagnosis for five common cancers in China: a multicentre, hospital-based, observational study[J/OL]. Lancet Public Health, 2021, 6(12): e877-e887. DOI: 10.1016/S2468-2667(21)00157-2.
44. Zeliadt SB, Hoffman RM, Birkby G, et al. Challenges implementing lung cancer screening in federally qualified health centers[J]. Am J Prev Med, 2018, 54(4): 568-575.
45. Wood DE, Kazerooni EA, Aberle DR, et al. NCCN guidelines insights: lung cancer screening, version 1.2025[J/OL]. J Natl Compr Canc Netw, 2025, 23(1): e250002. DOI: DOI10.6004/jnccn.2025.0002.
46. Horeweg N, Scholten ET, de Jong PA, et al. Detection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers[J]. Lancet Oncol, 2014, 15(12): 1342-1350.
47. Sverzellati N, Silva M, Calareso G, et al. Low-dose computed tomography for lung cancer screening: comparison of performance between annual and biennial screen[J]. Eur Radiol, 2016, 26(11): 3821-3829.
48. Gierada DS, Pinsky PF, Duan F, et al. Interval lung cancer after a negative CT screening examination: CT findings and outcomes in National Lung Screening Trial participants[J]. Eur Radiol, 2017, 27(8): 3249-3256.
49. Yousaf-Khan U, van der Aalst C, de Jong PA, et al. Final screening round of the NELSON lung cancer screening trial: the effect of a 2.5-year screening interval[J]. Thorax, 2017, 72(1): 48-56.
50. Veronesi G, Maisonneuve P, Spaggiari L, et al. Diagnostic performance of low-dose computed tomography screening for lung cancer over five years[J]. J Thorac Oncol, 2014, 9(7): 935-939.
51. Wu H, Zhang Y, Hu H, et al. Ground glass opacity featured lung adenocarcinoma in teenagers[J]. J Cancer Res Clin Oncol, 2021, 147(12): 3719-3724.
52. Jiang B, Han D, van der Aalst CM, et al. Lung cancer volume doubling time by computed tomography: a systematic review and meta-analysis[J/OL]. Eur J Cancer, 2024, 212: 114339. DOI: 10.1016/j.ejca.2024.114339.
53. Prokop M, Schaefer-Prokop C, Jacobs C, et al. Aggressiveness-guided nodule management for lung cancer screening in Europe-justification for follow-up intervals and definition of growth[J]. Eur Radiol, 2025, 36(1): 122-134.
54. Deng C, Chen Z, Bai J, et al. Clinical characteristics and progression of pre-/minimally invasive lung adenocarcinoma harboring ALK or RET rearrangements: a retrospective cohort study[J]. Transl Lung Cancer Res, 2023, 12(12): 2440-2447.
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