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. 2025 Nov;35(11):7156-7166.
doi: 10.1007/s00330-025-11576-3. Epub 2025 Apr 24.

Incidence rate and malignancy risk in new nodules in a lung cancer screening programme

Andrew W Creamer  1 , Carolyn Horst  1 , Priyam Verghese  1 , Ruth Prendecki  1 , Amyn Bhamani  1 , Helen Hall  1 , Jennifer L Dickson  1 , Sophie Tisi  1 , Chuen Ryan Khaw  1 , John McCabe  1 , Kylie Gyertson  2 , Anne-Marie Hacker  3 , Laura Farrelly  3 , Allan Hackshaw  3 , Arjun Nair  2 , Anand Devaraj #  4   5 , Sam M Janes #  6 ; SUMMIT consortium
Collaborators, Affiliations

Incidence rate and malignancy risk in new nodules in a lung cancer screening programme

Andrew W Creamer et al. Eur Radiol. 2025 Nov.

Abstract

Introduction: There is limited evidence for the malignancy risk posed by new nodules appearing at annual screening rounds or at short-term interval nodule follow-up (NFU) CTs in lung cancer screening programmes. We investigated incidence rate and malignancy risk in new nodules appearing at NFU and at first annual CT in a screening cohort and investigated nodule and participant characteristics which predicted malignancy.

Methods: 11,566 participants underwent baseline CT screening between April 2019 and April 2020. CTs were read in conjunction with computer-aided detection software with semi-automated volumetry. Nodule management was based on British Thoracic Society guidelines, with the addition of a lower threshold for new solid nodules appearing at incident rounds; those ≥ 30 and < 200 mm3 underwent a further 3-month interval scan, and new nodules ≥ 200 mm3 were referred directly for definitive investigation.

Results: New nodules were identified in 8.4% of participants at NFU-CT and 11.1% at Y1. 0.63% (95% confidence interval (CI) 0.016-3.433) of new nodules at NFU-CT and 2.98% (95% CI 1.83-4.57) at annual CT proved malignant. Malignancy risk in new nodules at Y1 was 1.67% in nodules < 30 mm3, 2.2% in nodules 30-200 mm3 and 11.0% in nodules > 200 mm3. No nodules with typical perifissural or subsolid morphology were malignant. There was no significant difference in age, smoking status, smoking history or predicted cancer risk between participants with new nodules which proved malignant and those which were benign.

Conclusion: Our findings validate the need for lower volume thresholds for further surveillance or definitive investigation in new solid nodules at annual scans. Malignancy risk in new nodules with subsolid or typical perifissural morphology and in new nodules appearing in a shorter time frame of NFU CTs is low.

Key points: Question What is the incidence and malignancy risk of new nodules appearing at annual and nodule follow-up interval CTs in lung cancer screening? Findings New nodules were seen in 11.1% and 8.4% of participants at annual low-dose CT and 3-month interval CT, respectively. Malignancy risk at annual CT increased with nodule size. Clinical relevance In a lung cancer screening programme, new nodules at annual and nodule follow-up CTs occur in around 1 in 10 participants. Lower size thresholds for further surveillance or definitive investigation should be considered compared to nodules at baseline CT.

Keywords: Cancer screening; Lung cancer; Pulmonary nodules (multiple); Pulmonary nodules (solitary).

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Conflict of interest statement

Compliance with ethical standards. Guarantor: The scientific guarantor of this study is Prof Sam Janes. Conflict of interest: A.W.C., C.H., J.L.D., S.T., H.H., P.V., R.P., A.B. and R.K. are all funded or part-funded through GRAIL as part of the SUMMIT Study. SUMMIT is sponsored and conducted by University College London and funded by GRAIL LLC through a research grant awarded to S.M.J. as principal investigator. S.M.J.’s full disclosures are as a Paid Advisory Board member AstraZeneca, Bard1 Bioscience, Achilles Therapeutics, Jansen. Assistance for travel to meetings from AstraZeneca, Takeda, and grant income from GRAIL Inc, Owlstone and share options from Optellum; BARD1 Lifescience. N.N. is supported by a Medical Research Council Clinical Academic Research Partnership (MR/T02481X/1). N.N. reports honoraria for non-promotional educational talks or advisory boards from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, EQRx, Fujifilm, Guardant Health, Intuitive, Janssen, Lilly, Merck Sharp & Dohme, Olympus and Roche. A.N. is part-funded through the UCLH Biomedical Research Centre. A.D.’s disclosures are personal fees from Boehringer Ingelheim, Roche, Galacto Biotech, Galapagos, Brainomix and Vicore. A.H.’s disclosures are consulting fees to Evidera and assistance for travel to meetings from GRAIL. Statistics and biometry: Statistical input for the SUMMIT study was provided by Allan Hackshaw. No additional complex statistical methods were necessary for this analysis. Informed consent: Written consent was obtained from participants at the point of determining study eligibility. Ethical approval: Ethical approval was obtained from an NHS Research Ethics Committee (17/LO/2004) and the NHS Health Research Authority’s Confidentiality Advisory Group (18/CAG/0054). Study subjects or cohorts overlap: All participants were part of the SUMMIT study; this is a large multi-faceted study which has generated a number of publications on a variety of aspects of lung cancer screening. This is the only paper looking at the question of newly-appearing nodules. Methodology: The SUMMIT study is a prospective observational cohort study with a predetermined nodule management protocol (including for new nodules). This analysis was performed as an observational study.

Figures

Fig. 1
Fig. 1
Participants undergoing low-dose CT at baseline, Y0 + 3-month nodule follow-up, Year 1 and Y1 + 3-month nodule follow-up timepoints. LDCT, low-dose CT; NFU-CT, nodule follow-up CT; Y0, year 0 (baseline); Y1, year 1. + To ensure the population of new nodules appearing at NFU-CT were representative of those appearing in the 3-month timeframe, participants where NFU-CT scans were performed > 180 days after Y0/Y1 were not included in the NFU-CT analysis. The reason for significant delays was primarily due to disruption from the SARS-CoV-2 pandemic. ‡ Second review was limited to nodules reported as new which proved malignant. * Participants with negative baseline LDCTs were randomised to scan or no scan at Y1 in a 1:1 ratio, therefore only a proportion of participants who had baseline LDCT underwent a further scan at Y1
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