The technology

EarlyCDT‑Lung (Oncimmune) is a blood test that measures a group of 7 autoantibodies (p53, NYESO‑1, CAGE, GBU4‑5, HuD, MAGE A4 and SOX2) to tumour-associated antigens related to lung cancer. It helps early detection of lung cancer in people with high risk and allows differentiation of benign or malignant nodules. In the early stages of lung cancer, autoantibodies and tumour-associated antigens are produced as the body's immune system's response to cancer antigens. Blood levels of autoantibodies are elevated in the earliest stage of lung cancer and are present at all stages of the disease.

EarlyCDT‑Lung test uses a standard enzyme-linked immunosorbent assay (ELISA). EarlyCDT‑Lung is available as a CE‑IVD kit, from a Clinical Laboratory Improvement Amendments registered laboratory in the US or from laboratories supported by Oncimmune's approved distributor network. Test results are based on a comparison of relative autoantibody levels to fixed thresholds. A sample is positive if at least 1 autoantibody is above a prespecified cut-off. EarlyCDT‑Lung has a high specificity and serves as a rule in test to identify people who need interventions such as PET‑CT or biopsy. The test may need to be repeated but the best number of times to repeat it is unknown.

Innovations

EarlyCDT‑Lung enables earlier and accurate diagnosis in people at high risk of lung cancer. This could mean treatment is offered early, giving improved outcomes. Also, it could save CT scan and radiologist resources and reduce waiting times.

Current care pathway

Pulmonary nodules are small growths in the lung, often found incidentally when having a chest X‑ray or CT scan. They may be malignant or benign.

The British Thoracic Society guidelines for the investigation and management of pulmonary nodules recommends that patients with nodules less than 5 mm in diameter or 80 mm3 in volume should be discharged. CT surveillance is recommended for larger nodules. The guideline recommends using the Brock model for the risk assessment of pulmonary nodules larger than 8 mm diameter or 300 mm3 volume. Based on an assessment with that model, people whose nodules have a malignancy risk above 10% have PET‑CT. Then malignancy risk is recalculated using the Herder model. People with risk less than 10% are offered CT surveillance and those with risk over 70% should be immediately considered for surgery. The guidelines recommend image-guided biopsy or excision biopsy. Or, they recommend CT surveillance guided by individual risk and patient preference for people with indeterminate pulmonary nodules (IPN; 10% to 70% risk of malignancy).

Quite often clinicians must rely on their judgement to assess risk, because validated risk models are only based on a few relevant risk factors.

NICE's guideline on the diagnosis and management of lung cancer recommends sputum cytology for investigation in people with suspected lung cancer who have centrally placed nodules and are unable to tolerate bronchoscopy or invasive tests. A contrast-enhanced chest CT scan is recommended for further diagnosis and to stage the disease. The guideline recommends PET‑CT as a first test after CT with a low probability of nodal malignancy (lymph nodes below 10 mm). MRI, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS‑TBNA) and endoscopic ultrasound-guide fine-needle aspiration (EUS‑FNA) are other methods that can diagnose and stage the disease.

Population, setting and intended user

EarlyCDT‑Lung will be used in addition to standard care for early detection of lung cancer in people at high risk. It can also be used in the risk classification of people with IPN found by chest CT or X‑ray. The test would be offered before deciding about CT surveillance (that is, after initial CT surveillance or after PET‑CT). This would mean patients with results showing increased risk of malignancy can begin treatment immediately.

The technology would probably be used in a secondary care setting by a member of the lung cancer multidisciplinary team.

Costs

Technology costs

The EarlyCDT‑Lung costs £600 (excluding VAT) per kit and each kit can run 10 samples, so £60 per test. The kit comes with all reagents for testing. The company estimates that staff time for each test will cost £10 for a laboratory running a reasonable volume of tests. This means the per patient cost is £70.

Costs of standard care

Cost of CT surveillance is £90 (NHS National tariff payment system HRG code RD22Z, CT scan of 1 area, with pre and post-contrast, 2019/20 tariff prices). With reporting, the scan is an additional £20.

Resource consequences

EarlyCDT‑Lung would be an additional cost to standard care. Resource use may reduce if it helps the early detection of lung cancer.

A National Institute for Health Research-funded study assessed the cost-effectiveness of EarlyCDT‑Lung in the cancer risk assessment of IPN compared with CT surveillance. At a cost of £70 for the test, the incremental cost effectiveness ratio is less than £2,500 per quality-adjusted life year (QALY) gained, depending on the test accuracy parameters used.

Edelsberg et al. (2018) assessed the cost-effectiveness of EarlyCDT‑Lung in early cancer detection compared with CT surveillance. Results were given of a model-based analysis in a cohort of 1,000 patients who had incidentally detected nodules of 8 mm to 30 mm and an intermediate risk of lung cancer, who were under CT surveillance only. It showed that cost per life-year gained was $18,029 and cost per QALY gained was $24,330. Using EarlyCDT‑Lung at a sensitivity and specificity of 28% and 98%, respectively, gave cost-effectiveness ratios of $18,454 and $24,833. The authors concluded that the use of EarlyCDT‑lung is likely to be cost saving.