A single tumour can be harmless or lethal, and doctors currently have no reliable way to tell the difference without invasive procedures. This project tackles the problem of overdiagnosis in cancer screening—finding cancers that would never cause symptoms, then treating them unnecessarily. The researchers will systematically review all existing evidence on biomarkers (biological signals from tissue, blood, or imaging) that might distinguish aggressive from indolent tumours in five cancers: lung, ovarian, prostate, oesophageal, and breast. They will then convene clinicians, researchers, and patient representatives to build a practical roadmap for deploying the most promising biomarkers in screening programmes. If successful, this work could shift cancer screening from a one-size-fits-all approach to a stratified one: people with indolent lesions could avoid surgery, chemotherapy, and the anxiety of a cancer diagnosis, while those with progressive disease receive earlier, more targeted treatment. The immediate output is a conceptual framework and research priorities, not a clinical test—but that framework is a necessary step toward making screening smarter, not just more extensive.
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Background Cancer early detection presents the challenge of balancing the interception of progressive lesions before they become invasive with avoiding overdiagnosis of indolent lesions that would otherwise not present clinically. Advances in cancer early detection research, coupled with deeper biological insights and technological innovations, raise the prospect of having biomarkers that differentiate indolent from potentially progressive cancers and using earlier endpoints in randomised screening trials as surrogates for cancer-specific mortality. Aims We aim to systematically review the evidence on biomarkers of progression (e.g. histological, omics-based, biochemical assays, imaging, and algorithmic) for five common cancers – lung, ovarian, prostate, oesophageal, and breast – that have screening programmes or trials and known precursor lesions. We intend to co-develop a conceptual framework and a roadmap for deploying the most promising biomarkers to optimise the benefit-harm balance in cancer early detection. Methods We will conduct an umbrella review of existing reviews of biomarkers of tumour progression and a scoping review to identify primary research for biomarkers for which a systematic review does not exist. Once we identify high-quality evidence on the most promising biomarkers based on their discriminative capacity, we will hold a consensus workshop with key stakeholders, including clinicians, researchers, screening experts, and patient and public representatives, to discuss the findings of our review and the testing scenarios that need to be evaluated through modelling. These discussions will lead to a conceptual framework of cancer progression to underpin a roadmap for applying these biomarkers across the cancer continuum and identifying the key research priorities. What value will the programme of work deliver Synthesising the latest evidence on biomarkers of tumour progression and engaging with stakeholders will enable developing strategies on advancing the research in the field and on implementing biomarkers with high quality evidence to detect relevant cancers at an earlier stage. This is a necessary step towards achieving the ambition of the NHS Long Term Plan in early cancer diagnosis.
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