Further insights into the clinical impact of annual screening with a multicancer blood test: Data analysis from NHS-Galleri

Primary supervisor: Peter Sasieni, Queen Mary University of London

Secondary supervisor: Mieke Van Hemelrijck, King’s College London

Project

Whether screening with blood-based early-detection tests for multiple cancers in addition to usual care has clinical utility was unknown until very recently. The NHS-Galleri randomised controlled trial enrolled 142,000 individuals to evaluate multi-cancer early detection (MCED) via cell-free DNA methylation (Sasieni P, Johnson P, et al., and, Swanton C. N Engl J Med. 2026). The clinical trial collected blood samples at baseline, 12, and 24 months, testing the screening arm prospectively while storing control arm samples. All participants are linked to the National Disease Registration Service to track multiple cancer types and clinical outcomes. Notably, the trial achieved excellent representation across the socioeconomic spectrum. While primary 3-to 4-year follow-up results are published, further longitudinal follow-up enables critical secondary and exploratory analyses.

The proposed PhD study will accelerate progress in the early detection of cancer.  Leading on from this landmark NHS-Galleri study, the successful candidate will contribute to several key analytical workstreams:

• Time to Diagnosis: Evaluating diagnostic resolution timelines for Galleri-positive participants compared against standard urgent suspected cancer pathways.
• Diagnostic Care Pathways: Conducting granular analyses of diagnostic investigations using data from the Guy’s Cancer Real-World Evidence Programme to inform health economics and resource planning.
• Predicted Mortality Modelling: Developing methods to predict cancer mortality from type and stage at diagnosis. Methodological work will address lead-time bias management and quantify the efficiency gains of using predicted versus observed mortality.
• Overdiagnosis Evaluation: Analysing cumulative cancer incidence convergence between arms by retrospectively testing stored control samples to assess excess diagnosis as a function of time from testing.
• Cancer Mortality Analysis: Performing simple inter-arm comparisons and nested analyses on stored control samples from participants who die from cancer (tracking deaths up to mid-2027/2028), supported by power-focused statistical simulations.
• Tumour Methylated Fraction: Investigating the prognostic value of methylation fractions at or prior to diagnosis, assessing its additive value over clinical staging, and tracking longitudinal variations across multiple samples.
• Survival Analysis: Evaluating post-diagnosis and post-detection survival stratified by participant and cancer characteristics.

Candidate background

• Proven experience managing and analysing large datasets using R, Python, Stata, or SAS.
• Proficient in survival analysis methodology and advanced techniques for handling missing data.
• A solid mathematical core, including linear algebra, calculus, and probability theory.
• Demonstrated ability to synthesize complex analyses into structured outputs, evidenced by a high-quality undergraduate report or postgraduate dissertation.
• Prior exposure to clinical trial reporting frameworks, particularly the generation or auditing of Tables, Listings, and Figures (TLFs), is highly advantageous.

Potential placements

1. Mieke Van Hemelrijck, Transforming cancer OUtcomes through research (TOUR) group, King’s College London
2.  Nitzan Rosenfeld, Barts Cancer Institute, Queen Mary University of London
3. Allan Hackshaw, CRUK & UCL Clinical Trials Centre, UCL/UCLH

References

1. Sasieni P, Johnson P, Round T, Warwick J, Jones H, Dolly S, Lee L, Lee Y, Kumar H, Liang W, Smittenaar R, Neal RD, Swanton C. Effect of Screening with Multicancer Early-Detection Test on Late-Stage Cancer Diagnosis. N Engl J Med. 2026 Sep 22. doi: 10.1056/NEJMoa2505723. Epub ahead of print. PMID: 42776074.
2. Neal RD, Dolly S, Johnson P, Jones H, Kumar SH, Lee LYW, Lee Y, Liang W, Round T, Smittenaar R, Warwick J, Sasieni P, Swanton C. Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial. Nat Med. 2026 Sep 22. doi: 10.1038/s41591-026-04652-8. Epub ahead of print. PMID: 42773209.
3. Sasieni P, Swanton C, Neal RD. The National Health Service-Galleri multicancer screening trial: explanation and justification of unique and important design issues. J Natl Cancer Inst. 2026 Apr 1;118(4):573-578. doi: 10.1093/jnci/djaf218. PMID: 40795803; PMCID: PMC13064514.
4. Sasieni P, Brentnall AR. More efficient, smaller multicancer screening trials. J Natl Cancer Inst. 2025 Mar 1;117(3):450-455. doi: 10.1093/jnci/djae251. PMID: 39400565; PMCID: PMC11884843.
5. Cuzick, Jack; Cafferty, Fay H; Edwards, Robert; Møller, Henrik; Duffy, Stephen W (2007). Surrogate endpoints for cancer screening trials: general principles and an illustration using the UK Flexible Sigmoidoscopy Screening Trial. Journal of medical screening, 14 (4). pp. 178-185. ISSN 0969-1413 DOI: https://doi.org/10.1258/096914107782912059