Background: In endometrial carcinoma (EC), preoperative classification is based on histopathological criteria, with only moderate diagnostic performance for the risk of lymph node metastasis (LNM). So far, existing molecular classification systems have not been evaluated for prediction of LNM. Optimized use of clinical biomarkers as recommended by international guidelines might be a first step to improve tailored treatment, awaiting future molecular biomarkers.

Aim: To determine the diagnostic accuracy of preoperative clinical biomarkers for the prediction of LNM in endometrial cancer.

Methods: A systematic review was performed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Studies identified in MEDLINE and EMBASE were selected by two independent reviewers. Included biomarkers were based on recommended guidelines (cancer antigen 125 [Ca-125], lymphadenopathy on magnetic resonance imaging, computed tomography, and F-fluorodeoxyglucose positron emission tomography/computed tomography [FDG PET-CT]) or obtained by physical examination (body mass index, cervical cytology, blood cell counts). Pooled sensitivity, specificity, area under the curve (AUC), and likelihood ratios were calculated with bivariate random-effects meta-analysis. Likelihood ratios were classified into (0.5-1.0 or 1-2.0), (0.2-0.5 or 2.0-5.0) or (0.1-0.2 or ≥ 5.0) impact.

Results: Eighty-three studies, comprising 18,205 patients, were included. Elevated Ca-125 and thrombocytosis were associated with a increase in risk of LNM; lymphadenopathy on imaging with a increase. Normal Ca-125, cytology, and no lymphadenopathy on FDG PET-CT were associated with a decrease. AUCs were above 0.75 for these biomarkers. Other biomarkers had an AUC <0.75 and incurred only impact.

Conclusion: Ca-125, thrombocytosis, and imaging had a and impact on risk of LNM and could improve preoperative risk stratification.

Implications For Practice: Routine lymphadenectomy in clinical early-stage endometrial carcinoma does not improve outcome and is associated with 15%-20% surgery-related morbidity, underlining the need for improved preoperative risk stratification. New molecular classification systems are emerging but have not yet been evaluated for the prediction of lymph node metastasis. This article provides a robust overview of diagnostic performance of all clinical biomarkers recommended by international guidelines. Based on these, at least measurement of cancer antigen 125 serum level, assessment of thrombocytosis, and imaging focused on lymphadenopathy should complement current preoperative risk stratification in order to better stratify these patients by risk.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738307PMC
http://dx.doi.org/10.1634/theoncologist.2019-0117DOI Listing

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