Incidence and lung cancer probability of new nodules in the UK lung screening trial

Background New nodules detected during lung cancer screening follow-up have a higher average malignancy risk than same-size baseline nodules. We aimed to characterize the incidence and malignancy risk of new nodules in the UK Lung Cancer Screening Trial (UKLS). Methods This study analysed data from the UKLS multicenter randomized controlled trial recruiting 4055 high-risk individuals (aged 50–75 years, with a LLPv2 risk of ≥4.5%) between 2011 and 2013. Our analysis included all non-calcified nodules registered as new at short-term (3-month) or 12-month follow-up. Volume and maximum volume doubling time (VDT max ) were analysed. Lung cancer diagnoses were confirmed by histology. Results Of 875 participants with follow-up CT scans, 131 (15%) developed 216 new solid nodules, yielding an overall participant-level malignancy rate of 3.8% (5/131); no malignancies were diagnosed in new subsolid nodules. New solid nodule incidence was 17% (72/432) at short-term and 8% (68/809) at 12-month follow-up. All 5 cancers were first detected at 12-month follow-up, where 7.4% (5/68) of participants with new solid nodules had cancer, while the risk was 0% (0/72) at short-term follow-up. At 12-months, new nodule malignancy probability was stratified by volume: 0% (95% CI: 0.0–21.6) for < 30 mm³ , 7.9% (2.0–21.5) for 30–200 mm³ , and 15.4% (3.1–43.5) for ≥ 200 mm³ ; and by VDT max : 2.0% (0.0–11.7) for ≥ 100 days, 18.8% (5.8–43.8) for 50–100 days, and 33.3% (5.6–79.8) for < 50 days. Conclusion New solid nodules at 12-month screening carry higher risk than short-term, and we validate 30mm³ as the critical volume threshold requiring at least further surveillance.