# Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study

Source: https://onco.cc/key-papers/paper-symplify-lancet-oncol-2023/  
OnCo record `paper-symplify-lancet-oncol-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In 5,461 people sent urgently to hospital with symptoms that might be cancer, the Galleri test was positive in three in four of those found to have cancer at higher stages but in about one in four with stage I cancer.

## Summary

SYMPLIFY (ISRCTN10226380) was a prospective observational study at 44 NHS hospital sites in England and Wales of the GRAIL methylation test in people aged 18 or older referred from primary care with non-specific symptoms or symptoms of gynaecological, lung or gastrointestinal cancer, run blinded to clinical outcome. Of 5,461 analysable participants, 368 (6.7%) had cancer. The test detected a cancer signal in 323, of whom 244 had cancer: positive predictive value 75.5% (95% CI 70.5 to 80.1), negative predictive value 97.6%, sensitivity 66.3% (61.2 to 71.1) and specificity 98.4% (98.1 to 98.8). Sensitivity rose with stage, from 24.2% (16.0 to 34.1) at stage I to 95.3% at stage IV. The predicted site of origin was accurate in 85.2%.

## Fields

- Kind: Key paper
- Last checked: 2026-10-29
- Journal: The Lancet Oncology
- Year: 2023
- DOI: 10.1016/S1470-2045(23)00277-2
- Authors: Nicholson BD, Oke J, Virdee PS, et al.
- Findings: Positive predictive value 75.5%; negative predictive value 97.6%.; Sensitivity 66.3% overall; 24.2% at stage I and 95.3% at stage IV.; Specificity 98.4%; site of origin accurate in 85.2%.
- What it means: In people who already have symptoms the test is more often right when positive, because cancer is commoner, but it still misses most stage I cancers, so a negative result cannot cancel an urgent referral.
- Caveats: Results were not returned to patients or doctors; the study measured accuracy, not effect on care.; Funded by GRAIL Bio UK.

## Sources

- Lancet Oncology 2023: SYMPLIFY: https://doi.org/10.1016/S1470-2045(23)00277-2
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37352875/
- ISRCTN10226380: https://www.isrctn.com/ISRCTN10226380

## Connected records

- fronts: [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- technologies: [Cell-free DNA methylation tests](https://onco.cc/technologies/cfdna-methylation-testing/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/)
- drugs: [Galleri](https://onco.cc/drugs/galleri/)
- companies: [GRAIL](https://onco.cc/companies/grail/)
- terms: [Positive predictive value (PPV)](https://onco.cc/terms/ppv/), [Sensitivity and specificity](https://onco.cc/terms/sensitivity-specificity/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

---
JSON: https://onco.cc/api/v1/entities/paper-symplify-lancet-oncol-2023.json