The goal of this observational study is to develop and evaluate a blood test for asymptomatic heavy smokers to screen for those at highest risk of developing lung cancer. The aim of this study is to develop, train, and validate a blood-based screening test designed to detect biomarkers associated with lung cancer. The study will utilize samples collected from 4 distinct cohorts.

1. Participants confirmed to have lung cancer
2. Participants without cancer
3. Participants with moderate risk of lung cancer (indeterminate)
4. Participants confirmed to have other types of cancers linked to smoking

The main question this study aims to answer is whether the blood test can detect existing early-stage lung cancer in heavy smokers without symptoms and to provide insights into device performance and long-term outcomes when scans show no nodules, benign findings, or indeterminate nodules.

Participants will provide blood samples at the start of the study and during follow-up visits at 12 and 24 months. Participants will share information about their smoking history, lung cancer status, and relevant medical history

Researchers will collect blood samples, process them, and analyze the biomarkers at the Everest Detection laboratory. No results will be shared with participants or their doctors. The study will run for about 48 months, including a 24-month enrollment period and 24 months of follow-up to track participants' health and lung cancer outcomes.

Inclusion Criteria:

All Participants:

• Understands the study and can provide written informed consent
• Willing and able to provide a blood sample
• Age 30-80
• Current or former smoker

Non-Cancer Cohort:

• Recent CT scan within 3 months AND
• No lung nodules (Lung-RADS 1) or benign/stable nodules

Indeterminate Cohort:

• Recent CT scan within 12 months AND
• Indeterminate lung nodules under active monitoring

Highly Suspicious or Confirmed Lung Cancer Cohort:

• Confirmed untreated lung cancer OR
• Highly suspicious lung nodules undergoing diagnostic work-up

Other Cancer Cohort:

- Confirmed, untreated cancer associated with smoking

Exclusion Criteria:

• Cancer diagnosis within the last 5 years
• Systemic therapy, radiation, or surgery for cancer within 1 year prior to enrollment
• Any history of hematologic malignancies or myelodysplasia
• Known infection with HIV, HCV, or HBV
• Active pregnancy

Both smokers that meet USPSTF criteria for annual LD-CT screening (age 50-80, smoked >20 pack years, quit <15yr ago if former smoker) to younger (>30 years) and lighter smokers (>10 pack years)

Individual participant data (IPD) will not be shared due to study-specific considerations and data use restrictions.