LAUSR

Simple Summary Early diagnosis of ovarian cancer is challenging due to vague symptoms and a lack of screening tools. We aimed to evaluate two simple, non-invasive urine biomarkers, CA125 and HE4, for the diagnosis of ovarian cancer in symptomatic women. Paired urine and serum samples were collected from women undergoing treatment for ovarian cancer (cases) or investigations for gynaecological symptoms (controls) and were tested for CA125 and HE4. This study found urine CA125 and HE4 levels to be higher in women with cancer compared to controls, and that a combination of urine CA125 and HE4 had a sensitivity that was similar to the currently used serum CA125 for the detection of ovarian cancer. This suggests that urine CA125 and HE4 may be useful non-invasive diagnostic tools to triage women for formal ovarian cancer investigations and could be used as point-of-care testing in the community or low resource settings. Abstract The symptoms of ovarian cancer are vague, and current risk assessment tools such as serum CA125 and transvaginal ultrasound scan fail to reliably detect the disease early. This study aimed to evaluate urine CA125 and HE4 as diagnostic biomarkers for ovarian cancer in symptomatic women. Paired urine and serum samples were collected from women undergoing treatment for ovarian cancer (cases) or investigations for gynaecological symptoms (controls). Biomarkers were measured using an automated chemiluminescent enzyme immunoassay analyser. Standard diagnostic accuracy metrics were calculated. In total, 114 women were included, of whom 17 (15%) were diagnosed with an epithelial ovarian malignancy. Levels of urine CA125 and HE4 were significantly elevated in women with ovarian cancer compared to controls [CA125: 8.5 U/mL (IQR: 2.4–19.5) vs. 2.3 U/mL (IQR: 1.0–6.4), p = 0.01. HE4: 12.0 nmol/L (IQR: 10.3–23.1) vs. 6.7 nmol/L (IQR: 3.4–13.6), p = 0.006]. Urine CA125 and HE4 detected ovarian cancer with an AUC of 0.69 (95% CI: 0.55–0.82) and 0.71 (95% CI: 0.69–0.82), respectively (p = 0.73). A combination of urine CA125 and HE4 at optimal thresholds had a sensitivity of 82.4% (95% CI: 56.6–96.2) and was comparable to the sensitivity of serum CA125 [88.2% (95% CI: 63.6–98.5)]. Larger studies are required to confirm our findings, standardise urine collection, and evaluate optimal biomarker thresholds. Urine CA125 and HE4 may be useful non-invasive diagnostic tools to triage women for formal ovarian cancer investigations.