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Updated: Feb 4, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Upstaging of screen-detected lung cancers during diagnostic assessment
Monica L Mullin1,2, Priyam Verghese1, Chuen R Khaw1
1Lungs for Living Research Centre, UCL Respiratory, University College London, London, UK.
Introduction:
Lung cancer is the leading cause of cancer-related death worldwide. Low-dose CT (LDCT) screening improves outcomes by detecting early-stage cancers as pulmonary nodules. As most are benign, diagnosing these nodules is challenging and often requires surveillance imaging. The aim of this study is to assess the frequency of cancer progression in a lung cancer screening study as measured by tumour stage (T-stage).
Methods:
SUMMIT is a prospective cohort study assessing implementation of lung cancer screening with LDCT in a high-risk population. Screen-detected lung cancers with clinical tumour stage cT1a-c at time of referral were included. Upstaging was defined as an increase in T-stage from referral to treatment. The date of death was obtained from the National Cancer Registration and Analysis Service. Cox proportional hazards analysis with adjustment for age, sex, Charlson Comorbidity Index and pack years was used to assess mortality between groups.
Results:
390 screen-detected cancers were stage cT1a-c at time of referral. Upstaging occurred more frequently in cT1a (n=48, 56%) compared with cT1b (n=83, 38%) or cT1c (n=34, 40%), p=0.01. The proportion of part-solid nodules was similar between groups (upstaged-N=47, 27%, vs not upstaged-N=45, 21%, p=0.19). 43% of tumours increased T-stage from referral to first treatment (n=165). In participants upstaged, time from referral to treatment was longer (upstaged: 84 days, 46-298 vs not upstaged: 72 days, 43-211, p=0.04). Adjusted overall survival analyses showed an association between upstaging and mortality (HR 1.68, 95% CI 1.13 to 2.51, p=0.01).
Conclusion:
Tumour upstaging occurred in nearly half of early-stage cases in a lung cancer screening population. Tumour upstaging was associated with longer time to treatment and poorer outcomes in this population.
Trial Registration Number:
NCT03934866.
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