Abstract
The utility of comprehensive surgical staging in patients with low risk disease has been questioned. Thus, a reliable means of determining risk would be quite useful. The aim of our study was to create the best performing prediction model to classify endometrioid endometrial cancer (EEC) patients into low or high risk using a combination of molecular and clinical-pathological variables. We then validated these models with publicly available datasets. Analyses between low and high risk EEC were performed using clinical and pathological data, gene and miRNA expression data, gene copy number variation and somatic mutation data. Variables were selected to be included in the prediction model of risk using cross-validation analysis; prediction models were then constructed using these variables. Model performance was assessed by area under the curve (AUC). Prediction models were validated using appropriate datasets in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A prediction model with only clinical variables performed at 88%. Integrating clinical and molecular data improved prediction performance up to 97%. The best prediction models included clinical, miRNA expression and/or somatic mutation data, and stratified pre-operative risk in EEC patients. Integrating molecular and clinical data improved the performance of prediction models to over 95%, resulting in potentially useful clinical tests.
Highlights
Endometrial cancer is the most common gynecologic cancer diagnosed in the United States, with an estimated 61,380 new cases and 10,920 deaths in 2017 [1]
Prediction models based on lymph node (LN) involvement to identify high risk endometrial cancer patients have a positive predictive value of around 20% in EEC [7,8] and rely on uterine factors obtained intra-operatively and/or on frozen pathologic evaluation
There are major risks associated with surgical staging and LN dissection; these include increased operative time, potential for blood loss associated with vascular injury, genitofemoral nerve injury, lymphocyst formation, and lymphedema [10,11,12,13]
Summary
Endometrial cancer is the most common gynecologic cancer diagnosed in the United States, with an estimated 61,380 new cases and 10,920 deaths in 2017 [1]. Prediction models based on lymph node (LN) involvement to identify high risk endometrial cancer patients have a positive predictive value of around 20% in EEC [7,8] and rely on uterine factors obtained intra-operatively and/or on frozen pathologic evaluation. Using these algorithms for prediction of LN involvement, it would be necessary to perform 4 to 8 lymphadenectomies to find one patient with true positive LNs [9]. Recurrence occurs in up to 8% of EEC patients with none of these risk factors [10]
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