Biomarkers for the early detection of lower gastrointestinal cancers in primary care: a systematic review and meta-analysis

A new systematic review and meta-analysis investigating biomarkers for the early detection of lower gastrointestinal cancers in primary care found some promising biomarkers, but further research is needed to validate their use in primary care to assess patients presenting with symptoms.

Lower gastrointestinal (GI) cancers represent a substantial public health problem, with over 1.8 million cases diagnosed worldwide in 2018. While many countries have organised colorectal cancer screening programmes, most patients with such cancers first present in primary care with symptoms. New approaches with non-invasive tests are required to help improve early detection and reduce the unnecessary use of resource-intensive, expensive, and invasive procedures such as colonoscopies. This review, carried out by researchers at the University of Melbourne, Cambridge and Leeds, investigated biomarkers that show sufficient promise to be evaluated in primary care for the early detection of lower GI cancers. This was part of a larger programme of work that also investigated biomarkers for upper GI cancers (Calanzani 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. doi: 10.1007/s12325-020-01571-z).

The research identified 378 unique biomarkers used for the detection of colorectal cancers, but only 35 of these were investigated by more than one study. Due to heterogeneity of designs, populations and samples, meta-analysis was only possible for two biomarkers: methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). Both were shown to have good performance. The sensitivity and specificity for colorectal cancer of mSEPT9 was 80.6% (95% CI 76.6-84.0%) and 88.0% (95% CI 79.1-93.4%) respectively, and for M2-PK was 81.6% (95% CI 75.2-86.6%) and 80.1% (95% CI 76.7-83.0%) respectively.

Included studies often investigated biomarkers in settings where cancer prevalence is higher (such as hospitals), or for patients who had already been referred for investigations (for whom the cancer risk is also higher). As these characteristics influence test performance, these biomarkers need to be further evaluated in primary care (where cancer prevalence is low) before their use can be recommended in this setting.

Paige Druce, the lead author in the study, said: “We identified some promising biomarkers, but there is little evidence to support their use in primary care at this stage. We need large-scale studies in low-prevalence populations in order to accurately evaluate the potential role of biomarkers to support diagnostic assessment in primary care and other community settings”.

Druce P, Calanzani N, Snudden C, et al. Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Lower Gastrointestinal Cancers: A Systematic Review and Meta-Analysis. Adv Ther, 2021. https://doi.org/10.1007/s12325-021-01645-6