Biomarkers for the early detection of upper-gastrointestinal cancers in primary care: a systematic review

A new systematic review guided by the CanTest Framework found that while there is a large number of biomarkers being developed for the detection of upper GI cancers, more evidence from evaluations in low-prevalence populations like primary care is still needed before their adoption in clinical practice can be recommended.

Cancers of the stomach, oesophagus, pancreas and biliary tract represent a significant burden worldwide, with over 2.1 million cases diagnosed worldwide in 2018. While most patients first present with symptoms in primary care, early diagnosis is challenging as initial symptoms are common and often intermittent. Substantial investment has been made to identify biomarkers for cancer detection, but most research is still carried out in laboratory and specialist settings. This new CanTest review, performed by researchers from the Universities of Cambridge,  Melbourne and Leeds, aimed to identify novel biomarkers for the early detection of upper gastrointestinal cancers which had been validated and show sufficient promise to be further evaluated in primary care.

While the research identified 431 unique biomarkers, only 35 of these were investigated in more than one study, and just four biomarkers (apolipoproteins apoAII-AT and apoAII-AEQ for pancreatic cancer and pepsinogens PGI and PGII for gastric cancer) showed some promise for further evaluations.  Many studies were carried out in a mix of high- and low-prevalence populations, including hospital patients, general population cohorts, screening populations, and patients presenting with symptoms. Due to wide variation in methods, populations, biomarkers, outcomes and comparisons, it was not appropriate to carry out meta-analysis. The team highlights the importance of research collaborations to avoid duplicate efforts, ensure more consistency in the use of biomarkers, and achieve appropriate samples when investigating populations where cancer prevalence is low.

CanTest Research Associate Dr Natalia Calanzani said: “Whilst there is a huge growth of research in this area, the evidence for any new individual or panels of biomarkers is still at an early stage, and we need more studies carried out in the intended populations like primary care. Then, we need to go beyond clinical performance, assessing implementation, patient safety and quality, and cost effectiveness in this setting before clinical adoption can be recommended”.

This review is part of a larger programme of work: a second review focusing on novel biomarkers for lower gastrointestinal cancers has also been carried out, and results are expected in early 2021.

Calanzani N, Druce PE, Snudden C et al. Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review. Adv Ther (2020). https://doi.org/10.1007/s12325-020-01571-z