Urinary biomarkers for the detection of ovarian cancer: a systematic review

Currently, the only definitive method for diagnosing ovarian cancer involves histological examination of tissue obtained at time of surgery or by invasive biopsy. Blood has traditionally been the biofluid of choice in ovarian cancer biomarker discovery; however, there has been a growing interest in exploring urinary biomarkers, particularly as it is non-invasive. In this systematic review, we present the diagnostic accuracy of urinary biomarker candidates for the detection of ovarian cancer. A comprehensive literature search was performed using the MEDLINE/PubMed and EMBASE, up to 1 April 2021. All included studies reported the diagnostic accuracy using sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. Risk of bias and applicability of included studies were assessed using the QUADAS-2 tool. Twenty-seven studies were included in the narrative synthesis. Protein/peptide biomarkers were most commonly described (n = 18), with seven studies reporting composite scores of multiple protein-based targets. The most frequently described urinary protein biomarker was HE4 (n = 5), with three studies reporting a sensitivity and specificity > 80%. Epigenetic (n = 1) and metabolomic/organic compound biomarkers (n = 8) were less commonly described. Overall, six studies achieved a sensitivity and specificity of >90% and/or an AUC > 0.9. Evaluation of urinary biomarkers for the detection of ovarian cancer is a dynamic and growing field. Currently, the most promising biomarkers are those that interrogate metabolomic pathways and organic compounds, or quantify multiple proteins. Such biomarkers require external validation in large, prospective observational studies before they can be implemented into clinical practice.