Redefining Early Lung Cancer Screening Through Imaging and Biomarker Advances

Lung cancer remains the leading cause of cancer death, claiming more lives than breast, prostate, and colon cancer combined.¹ Updated data show that 5-year survival rates have increased to approximately 30%, largely due to stage shift and modern therapies.² The National Lung Screening Trial (NLST) demonstrated a 20% mortality reduction with low-dose computed tomography (LDCT) vs chest X-ray; the NELSON trial (ISRCTN63545820)confirmed a 24 to 26% reduction using volumetric CT, with women deriving greater benefit.^1,3 Yet its uptake remains below 20%.⁴

“If lung cancer is caught early, the outlook is completely different. Stage IV survival is under 10%, but stage I can be close to 90%. Early detection means we can often do a curative surgery and help patients live disease-free, which not only improves survival but also quality of life.” – Eric L. Grogan, MD, MPH.

“The state of Kentucky is a great example of what happens when screening programs are done well. Even with only about 20% of eligible people getting screened, they’ve already seen fewer late-stage cancers and better survival. That shows how powerful screening can be when implemented effectively.” – Stephen A. Deppen, PhD

What are the current best practices for lung cancer detection?

The United States Preventive Services Task Force recommends annual LDCT for adults 50 to 80 years of age with at least 20 pack-years and 15 or fewer years since quitting.⁵ Despite coverage, fewer than 18% of eligible individuals are screened.⁴ Barriers to screening include stigma, fatalism, and complexity of shared decision-making.

The Lung CT Screening Reporting and Data System (Lung-RADS), introduced in 2014 and updated in 2019 and 2022, standardizes reporting and reduces false positives compared to early trial data.^6,7 However, these eligibility criteria still miss many cases; only approximately 40% of patients diagnosed with lung cancer would have qualified under current rules.

Risk-based models like PLCOm2012 and Vanderbilt’s Thoracic Research Evaluation and Treatment (TREAT 2.0) improve the identification of high-risk patients, including women and non-smokers.⁸ The TREAT 2.0 model incorporates a novel method addressing missing data in predictive modeling: the pattern submodel approach.

What are some key advances in early lung cancer detection and risk assessment?

A landmark randomized controlled trial published in The New England Journal of Medicine demonstrated that electromagnetic navigational bronchoscopy (ENB) is non-inferior to CT-guided transthoracic biopsy for diagnosing peripheral lung nodules. Led by Fabien Maldonado, MD, MSc, the study showed ENB provides comparable diagnostic accuracy while significantly reducing complications, with pneumothorax occurring in approximately 1% of ENB cases compared with nearly 30% for CT-guided biopsy.⁹ This advance positions ENB as a safer, first-line option for tissue sampling in patients with suspicious lung nodules and represents a major step forward in early lung cancer detection and patient safety.

“These findings support a shift toward navigational bronchoscopy as a preferred diagnostic approach for appropriate patients, offering comparable accuracy with far fewer risks.” — Fabien Maldonado, MD, MSc,

Beyond procedural advances, several technologies are reshaping early detection and risk assessment:

• Imaging: AI tools such as Sybil predict 6-year lung cancer risk from LDCT; Optellum’s FDA-cleared platform supports nodule management and prevents loss to follow-up. Radiomics models such as computer aided nodule analysis and risk yield (CANARY) and benign vs aggressive nodule evaluation using radiomic stratification (BRODERS) refine risk stratification for adenocarcinoma and indeterminate nodules.^10-12
• Biomarkers: DELFI FirstLook Lung and Biodesix Nodify CDT/XL2 help triage screening and indeterminate nodules, reducing unnecessary biopsies.^13,14
• Multimodal Prediction: Combining imaging, electronic health records, and biomarkers improves diagnostic accuracy and supports personalized care. These innovations promise dynamic screening intervals and better patient experience.

How did the VERITAS trial contribute to diagnostic innovations in lung cancer?

The VERITAS trial (NCT06707688) showed that navigational bronchoscopy is noninferior to CT-guided biopsy for 10 mm to 30 mm nodules, with dramatically fewer complications.⁹ Robotic bronchoscopy with cone-beam CT boosts yield for small nodules. Cryobiopsy offers larger samples for early lesions. These advances reduce harm and accelerate diagnosis, aligning with patient priorities for the ‘right test first.’

What are some of the disparities in screening implementation and equity?

Screening uptake remains low, with disparities among rural populations, veterans, and underserved groups.¹⁵ However, Kentucky’s collaborative approach demonstrates real-world success. Barriers to access include stigma, fatalism, and logistical complexity, and patient-reported outcomes highlight anxiety (‘scanxiety’) and the need for empathetic communication and timely results. Programs that integrate navigation, smoking cessation, and structured reporting improve patient adherence and trust.

How will lung cancer screening evolve in the future?

Precision screening will integrate dynamic risk models, biomarkers, and adaptive trials, and multicancer early detection blood tests (e.g. GRAIL) may augment—not replace—LDCT. Pragmatic, adaptive trials will also accelerate evidence generation and patient-centered outcomes. Overall, expanding indications to capture non-smoker risk factors and tailoring intervals based on combined imaging and biomarker data will define the next era of lung cancer prevention.

References

1. de Koning HJ, van der Aalst CM, de Jong PA, et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. N Engl J Med. 2020;382(6):503-513. doi:10.1056/NEJMoa1911793
2. The American Cancer Society medical and editorial content team. Lung Cancer Survival Rates. American Cancer Society. Updated June 27, 2025. Accessed January 19, 2026.
3. National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365(5):395-409.doi:10.1056/NEJMoa1102873The
4. Gudina AT, Kamen CS, Hirko KA, et al. Lung Cancer Screening Uptake under the Revised United States Preventive Services Task Force Guideline: Assessing Disparities. Cancer Epidemiol Biomarkers Prev. 2025;34(1):35-41. doi:10.1158/1055-9965.EPI-24-0725
5. U.S. Preventive Services Task Force, Krist AH, Davidson KW, et al. Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. JAMA. 2021;325(10):962-970.doi:10.1001/jama.2021.1117
6. Lung CT Screening Reporting & Data System (Lung-RADS®) v2022. American College of Radiology. https://www.acr.org/Clinical-Resources/Clinical-Tools-and-Reference/Reporting-and-Data-Systems/Lung-RADS
7. Martin M, Kanne JP, Broderick L, et al. RadioGraphics Update: Lung-RADS 2022. RadioGraphics. 2023; 42 (11). doi:10.1148/rg.230037
8. Deppen, SA, Blume JD, Aldrich MC, et al. Predicting lung cancer prior to surgical resection in patients with lung nodules. J Thorac Oncol. 2014;9(10):1477-1484. doi:10.1097/JTO.0000000000000287
9. Lentz, RJ, Frederick-Dyer K, Planz VB, et al. Navigational bronchoscopy or transthoracic needle biopsy for lung nodules. N Engl J Med. 2025;392(21):2100-2112. doi:10.1056/NEJMoa2414059
10. McKee BJ, McKee AB, Flacke S, et al. Initial experience with a free, high-volume, low-dose CT lung cancer screening program. J Am Coll Radiol. 2013;10(8):586-592. doi:10.1016/j.jacr.2013.02.015
11. Optellum receives FDA clearance for the world’s first AI-powered clinical decision support software for early lung cancer diagnosis. News Release. Optellum. March 23, 2021. Accessed January 13, 2026. https://optellum.com/fda-clearance/
12. Refined tool aids in lung cancer diagnosis. News Release. Vanderbilt University Medical Center. February 5, 2024. Accessed January 13, 2026. https://discoveries.vanderbilthealth.com/2024/02/refined-tool-aids-in-lung-cancer-diagnosis/
13. FirstLook Lung: Fragmentomics-based blood test for lung cancer screening. DELFI Diagnostics. https://delfidiagnostics.com/healthsystems/
14. Nodify Lung®: CDT and XL2 tests for indeterminate pulmonary nodules. Biodesix. https://www.biodesix.com/tests/nodify-lung
15. Wiener RS, Gould MK, Arenberg DA, et al. An official American Thoracic Society/American College of Chest Physicians policy statement: implementation of low-dose computed tomography lung cancer screening programs in clinical practice. Am J Respir Crit Care Med. 2015;192(7):881-891. doi:10.1164/rccm.201508-1671ST