Does screening with the Galleri test in the NHS reduce the likelihood of a late-stage cancer diagnosis?

INTERVENTION: A prospective, randomised, controlled trial to assess the performance and clinical utility of a multi‐cancer early detection test for population screening in the UK when added to standard of care. Randomisation will be to the intervention arm, with blood collection and evaluation of the test or to the control arm, where blood samples are collected and will be stored for potential future evaluation but participants do not receive test results. All participants should continue to participate in routine NHS screening. Unless diagnosed with cancer, participants in both arms will be asked to return for annual visits at approximately 12 and 24 months. All participants whether test positive, test negative, or not tested will be followed for cancer and associated outcomes via NHS dataset linkages. Participants in the intervention arm who test positive will be referred for standard of care investigations and treatment in the NHS. CONDITION: Multi cancer early detection in people without symptoms ; Cancer PRIMARY OUTCOME: ; 1. Incidence and stage at diagnosis for cancer types that are stageable (e.g., with available staging systems) measured using patient records.; Cancer is defined as any of the following cancers:; ? Invasive solid cancer, excluding basal cell carcinoma and squamous cell carcinoma of the skin; ? Haematologic malignancies, including lymphoma, lymphoid leukemia,; myeloma/plasma cell neoplasm, myeloid neoplasms (including myelodysplastic and myeloproliferative neoplasms with behaviour code 3 based on ICD‐O‐3.2).; The following cancer types are not routinely staged and will therefore be excluded from the analysis of this primary objective: brain cancers, leukemias, cancers of unknown primary.; SECONDARY OUTCOME: ; Measured using patient records:; 1. Incidence and stage at diagnosis for cancer types that are stageable (e.g., with available staging systems) at other timepoints.; 2. Mortality at 16‐18 months of follow‐up for a pre‐specified group of cancer types, at years 3 and 6 after the last study visit, and at 7‐years post‐randomisation based on cancers diagnosed within an average of 40‐42 months of randomisation.; ; Safety endpoints (measured throughout the study):; 3. Among all test positive cases, number of follow‐up procedures and number of invasive procedures (including all biopsies, surgical interventions, bronchoscopy, thoracoscopy and endoscopy) to achieve diagnostic resolution (i.e. cancer diagnosis, non‐cancer diagnosis, or no diagnosis and discharge from the diagnostic follow‐up); 4. Number and type of invasive procedures performed in false positive cases;; 5. Number of complications and deaths resulting from diagnostic procedures;; 6. Radiation exposure measured in mSv per participant due to test result‐directed evaluations;; 7. Among all test positive cases, psychological impact, including anxiety, measured after Galleri test, after diagnostic resolution and at 12 months post testing using the short‐form State Trait Anxiety Index‐6 (STAI), a six‐item validated measure of state anxiety.; ; Healthcare resource utilisation endpoints:; 8. The data collected may be used to conduct future exploratory economic analyses, and will include: Number and types of medical encounters and cancer‐specific diagnostic and treatment procedures, including clinical lab visits, imaging tests, invasive tests, and clinic visits.; INCLUSION CRITERIA: 1. Participants must be at 50‐77 years of age, inclusive, at the time of data extraction from NHS datasets or GP records used to identify potential participants; and 2. Capable of giving signed and legally effective informed consent, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol. Consent provided by a legally authorised representative is not permitted in this protocol.