Circulating biomarkers for the preoperative diagnosis of uterine sarcoma: A systematic review and meta-analysis

Objective

A way to improve the early diagnosis of uterine sarcoma is by identifying circulating protein biomarkers that allow for differentiation between uterine sarcoma and benign leiomyomas. However, to date, no systematic review has gathered data on the diagnostic accuracy of these biomarkers as diagnostic tools for uterine sarcomas.

Methods

We performed a systematic review and meta-analysis. An electronic search was conducted using PubMed, EMBASE, Web of Science, and CENTRAL (Cochrane) to identify clinical studies investigating the potential role of circulating biomarkers for the diagnosis of uterine sarcoma. We selected only studies that compared patients with a histologically confirmed diagnosis of leiomyoma versus uterine sarcoma. This study was conducted according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies statement.

Results

A total of 20 observational studies were included, with a total of 13 biomarkers. Five studies reported data on diagnostic accuracy, including sensitivity and specificity. Lactate dehydrogenase levels showed a statistically significant difference between patients with uterine sarcoma and controls with leiomyoma (p < 0.001), with a sensitivity and specificity ranging between 0.47 and 1.00 and 0.86 to 1.00, respectively. Three studies reported data on diagnostic accuracy of carbohydrate antigen 125: the estimates for sensitivity and specificity ranged from 0.43 to 0.64 and 0.50 to 0.77, respectively, with substantial heterogeneity between the studies. Data on diagnostic accuracy for C-reactive protein was available for two studies, with sensitivity and specificity ranging between 0.84 and 0.87 and 0.83 to 0.89, respectively. Data for two biomarkers, human epididymal protein 4 and D-dimer, were insufficient, as each was evaluated in only one study.

Conclusions

This systematic review and meta-analysis showed that the most encouraging results were available for lactate dehydrogenase. Other biomarkers may also prove to be useful tools in differentiating between leiomyomas and uterine sarcomas; however, further studies are needed to replicate these findings.