Assessing a biomarker platform for stratifying indeterminate pulmonary nodules, protocol for the SPOT IT randomized trial

BACKGROUND: Millions of lung nodules are detected every year during routine computed tomography imaging. While most are benign, some represent early-stage lung cancer and require prompt diagnosis as survival worsens with advanced stages. The Lung Cancer Prediction score is a computed tomography-based radiomic biomarker used to risk-stratify pulmonary nodules. Observational studies have shown promising results, but it remains unclear if the use of this biomarker improves patient management. METHODS: SPOT IT is a multicenter, open-label, randomized controlled superiority trial. Adult patients (35 years and older) referred for evaluation of an incidentally detected lung nodule 8-30 mm in size who meet all eligibility criteria are currently being enrolled. Participants are randomized in a 1:1 ratio to receive either usual care combined with the Lung Cancer Prediction score or usual care alone. Randomization is conducted using permuted blocks of variable size, stratified by study center and nodule size (≤1.5 cm, >1.5 cm). The primary outcome is appropriate initial nodule management, defined as imaging surveillance for benign nodules and additional diagnostic procedures or definitive therapy for malignant nodules. Secondary outcomes include change in management, unnecessary invasive procedures for benign nodules, and time to diagnosis for malignant nodules. The study was approved by the Vanderbilt University Medical Center (single Institutional Review Board) and is being conducted with waiver of consent. Enrollment began in October 2024 and approximately 400 patients are expected to be enrolled by the time of completion. DISCUSSION: SPOT IT is an ongoing multicenter randomized controlled trial assessing the impact of a commercially available radiomic prediction score on patient management. Results from this trial might help inform the care of patients with pulmonary nodules and clarify the role of the biomarker in routine clinical practice. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov (NCT06638398) prior to opening. Registered on October 09 2024.