Dec. 09, 2025
Despite decreasing prevalence of cigarette smoking, lung cancer continues to be the most common and deadliest malignancy across genders. While the five-year survival rate of lung cancer remains low, it has started to improve over the last few years. This progress has largely been attributed to a stage shift increasing the proportions of early-stage lung cancers and improved therapies for locally advanced and metastatic disease. The stage shift is attributed to the implementation of lung cancer screening and the increased detection of incidental lung nodules. However, there are many remaining challenges.
More than 93 million CT scans, many of them imaging the lungs, are performed annually in the United States. The detection of lung nodules continues to dramatically increase; more than 1.6 million nodules are detected in the U.S. annually. Most of these nodules are incidentally detected and guideline-based follow-up for these nodules remains suboptimal (50% to 65%). Lack of timely communication of nodule diagnoses to patients and suboptimal patient adherence with follow up results in stage progression and decreased treatment survival.
Unfortunately, implementation of structured programs to systematically capture relevant incidental lung nodules and facilitate guideline-based follow-up is subject to several challenges, including nodule identification, care coordination and burnout by primary healthcare professionals.
Furthermore, nodule management is currently largely based on practice guidelines, expert opinion and patient preferences, and there remains a lack of clinically applicable biomarkers. Remaining challenges include the delayed identification of lung cancers (false-negatives), false-positive diagnoses (95% of lung nodules are benign), iatrogenic morbidity, and mortality due to overdiagnosis and overtreatment. The clinical implementation of structured incidental lung nodule programs in conjunction with effective biomarkers for lung nodule management is urgently needed.
In collaboration with Illuminate, Mayo Clinic in Rochester, Minnesota, implemented a structured incidental lung nodule management program in May 2024. The results were published in the October 2025 issue of the Journal of Thoracic Oncology.
The program started in December 2023, with a retrospective analysis covering December 2023 to May 2024. Natural language processing software by Illuminate captures all relevant lung nodules reported in all CT studies imaging the chest across the Rochester outpatient and inpatient practice. Electronic health records (EHRs) of patients with incidental lung nodules are reviewed by a team of RN-level nurse navigators, and nodules are classified as closed — for example, stable nodules and active cancer — engaged, meaning appropriate follow-up initiated by primary care, or re-engaged-incidental, known as the initial intervention group. All patients with engaged or re-engaged-incidental nodules with a primary health professional at Mayo Clinic are enrolled into a surveillance program.
Between December 2023 and July 2025, 27,284 nodules were identified and reviewed, excluding all nodules detected on CTs ordered by Medical Oncology or Radiation Oncology for patients receiving active cancer therapy or surveillance. Of the 6,979 nodules reviewed, 87% were engaged and 13% (n = 899) were re-engaged-incidental missed nodules. These nodules triggered 389 follow-up chest CTs, 107 visits to Mayo Clinic's Lung Nodule, Mass and Adenopathy Clinic (LNMAC), 50 PET-CTs, six bronchoscopies, and two CT-guided lung biopsies. Nine patients (1%) were diagnosed with lung cancer.
The nurse navigators use the EHR and letters to communicate with health professionals and patients. Follow-up testing is facilitated by sending prepared EHR orders to health professionals. The program continues to run smoothly and is associated with an extremely high level of health professional satisfaction.
Mayo Clinic is working to integrate internally developed radiomics models differentiating benign and malignant lung nodules — benign versus aggressive nodule evaluation using radiomic stratification (BRODERS) — and risk-stratifying lung adenocarcinomas — computer-aided nodule analysis and risk yield (CANARY) and virtual biopsy — into the workflow for all engaged and re-engaged-incidental lung nodules larger than 6 mm to further improve the management of incidental lung nodules in Mayo Clinic's LNMAC.
For more information
Anderson R, et al. A systematic approach to appropriate guideline-based management of incidentally detected pulmonary nodules the Mayo Clinic experience. Journal of Thoracic Oncology. 2025;20(suppl 1):S71.
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