Advancing Precision Lung Cancer Surveillance and Outcomes in Diverse Populations

Proportion of patients who complete guideline-recommended post-treatment chest CT surveillance within prespecified rolling surveillance windows. Guideline adherence will be defined using ±1-month and ±2-month allowable windows around each recommended surveillance time point. Semi-annual surveillance (Years 0-2) will be assessed at recommended months 6, 12, 18, and 24, with adherence defined as completing a CT within months 5-7 or 4-8, 11-13 or 10-14, 17-19 or 16-20, and 23-25 or 22-26, respectively. Annual surveillance (Years 3-5) will be assessed at recommended months 36, 48, and 60, with adherence defined as completing a CT within months 35-37 or 34-38, 47-49 or 46-50, and 59-61 or 58-62, respectively. Patients will be censored at recurrence, death, loss to follow-up, or end of study.

Surveillance begins at completion of curative-intent therapy (surgery or SBRT ± adjuvant therapy), and only routine surveillance scans are included. In Years 1-2, surveillance is guideline-concordant if CTs are completed within rolling 4-8-month intervals following either treatment completion or the prior surveillance CT. In Years 3-5, surveillance is guideline-concordant if CTs occur within rolling 10-14-month intervals from the prior CT. Patients are censored at recurrence, death, loss to follow-up, or end of study period.

Time from completion of curative-intent therapy to the first documented cancer recurrence (local, regional, or distant). Recurrence will be identified using structured electronic health records (EHR) recurrence fields, validated recurrence-detection algorithms, cancer registry linkage, and natural language processing (NLP) based extraction from radiology reports and clinical notes. Patients will be censored at death without recurrence, loss to follow-up, or completion of 5-year follow-up.

Time from completion of curative-intent therapy to diagnosis of a metachronous second primary lung cancer (SPLC). SPLC will be defined using standard criteria, including AJCC TNM staging, histologic distinction from the index tumor, cancer registry confirmation, and pathology report verification. Among patients who develop SPLC, we will evaluate stage at SPLC diagnosis, histologic subtype (including bronchioloalveolar carcinoma), and receipt of adjuvant therapy. Patients will be censored at death without SPLC, recurrence without SPLC, or completion of follow-up. This outcome will be analyzed as a time-to-event measure consistent with other survival endpoints.

Time from completion of curative intent treatment to death from any cause. Vital status will be ascertained through institutional cancer registries, the National Death Index, and state death certificate data.

Time from completion of curative-intent treatment to death attributed specifically to lung cancer, analyzed under a competing-risk framework in which non-lung cancer deaths are treated as competing events. Cause of death will be determined using institutional cancer registry data and National Death Index linkage.

Classification of recurrence mode at the time of first recurrence. Recurrences will be categorized as:

• Surveillance detected: Identified during routine surveillance CT imaging in asymptomatic patients.
• Symptom detected: Identified after clinical symptoms prompted diagnostic evaluation.

Detection mode will be determined using electronic health record (EHR) documentation and natural language processing (NLP) extraction from radiology reports and clinical notes. Timing of recurrence (time to event) will be evaluated separately; early vs. later surveillance detection will be described, but has no clinical implications if timing windows shift.

Classification of metachronous second primary lung cancer (SPLC) as either:

Surveillance-detected: Identified during routine surveillance CT imaging in asymptomatic patients.

Symptom-detected: Identified after new or worsening symptoms prompted diagnostic evaluation.

Detection mode will be determined using EHR documentation and NLP extraction from radiology reports and clinical notes.

Microsimulation-projected overall and lung cancer-specific survival under semi-annual versus annual CT surveillance schedules. The model will be calibrated using recurrence, SPLC, and mortality data from Aims 1-2 and extrapolated to national incidence patterns using SEER data.

Measure Description:

Difference in projected survival outcomes between semi-annual and annual surveillance strategies, reported as:

• Mean life expectancy (life-years)
• Five-year, ten-year, and lifetime survival probabilities
• Hazard of lung cancer-specific death

Model estimates will be derived from a calibrated Markov microsimulation model informed by Aims 1-2 and extrapolated using SEER incidence.

Patients will be categorized into one of four mutually exclusive surveillance patterns based on completed post-treatment surveillance CT imaging from 0-5 years following curative intent therapy:

• Semi-Annual Adherence: Consistent completion of surveillance CT scans within guideline-concordant 4-8 month intervals during Years 1-2, followed by 10-14 month intervals during Years 3-5.
• Annual Only Adherence: Completion of at least annual surveillance (10-14 month intervals) during Years 1-5, but not meeting semi-annual criteria in Years 1-2.
• Irregular/Other Surveillance: Completion of ≥1 surveillance CT scan during follow-up, but not meeting semi-annual or annual adherence definitions.
• No Surveillance: No documented surveillance CT scan within 12 months of treatment completion.

Intensity of surveillance CT use, measured as scans per person time and/or completion of guideline-recommended surveillance intervals

Surveillance CT scans that trigger additional diagnostic evaluation (biopsy, PET CT, or repeat imaging) without a lung cancer diagnosis (recurrence or SPLC) within 6 months of the index scan. Results will be classified as true positive, false positive, true negative, or false negative using cancer registry data and EHR documentation

Frequency and type of diagnostic procedures, both invasive and non-invasive, performed following surveillance CT imaging, including transthoracic biopsy, transbronchial biopsy, bronchoscopy, and PET-CT.

Complications occurring within 7 days and 30 days of invasive diagnostic procedures (transthoracic, transbronchial, or surgical biopsies), including:

• Pneumothorax
• Pulmonary hemorrhage
• Acute respiratory failure
• Acute renal failure
• Contrast allergy requiring hospitalization
• Acute myocardial infarction

Classification of recurrence site as local, regional, or distant, based on cancer registry definitions.

Time to treatment initiation following recurrence or SPLC diagnosis, and classification of treatment modality, including surgery, SBRT, targeted therapy, and immune checkpoint inhibitor therapy.

Model estimated timing of recurrence and SPLC detectability and symptom onset, and projected proportion detected through surveillance imaging versus symptom-prompted evaluation under alternative surveillance strategies.

Measure Description: Projected distributions of:

• Time to detectability
• Time to symptom onset for recurrence and SPLC. Additionally, the model will estimate the proportion of cases detected via surveillance imaging versus symptomatic presentation under each strategy. Results will be reported as absolute percentage differences and median time gained to detection.

Sensitivity analyses evaluating population-level outcomes under varying surveillance uptake levels (e.g., 50%, 70%, 90% adherence), including projected lung cancer deaths averted, earlier detection, false positive CTs, and downstream diagnostic complications.

Measure Description: Projected population impacts under alternative surveillance schedules and uptake levels, including:

• Lung cancer deaths averted per 1,000 patients
• Life years gained per 1,000 patients
• Additional false positive CTs per 1,000 patients
• Additional biopsy-related complications per 1,000 patients