Current challenges and emerging tools in endometrial cancer diagnosis

The diagnostic process of endometrial cancer includes imaging methods such as trans-vaginal ultrasound, along with procedures to obtain endometrial tissue for histologic evaluation. Common techniques for tissue sampling include Pipelle endometrial biopsy, hysteroscopy, and dilation and curettage, which are used to confirm the diagnosis, determine tumor histology, grade, and molecular profile. However, diagnostic algorithms for endometrial cancer differ significantly across countries, influenced by local resources, protocols, and the availability of diagnostic methods. These variations include differences in the endometrial thickness threshold for recommending a biopsy and the choice of the initial diagnostic test. Moreover, patients often have multiple tests and appointments before a definitive diagnosis, although only 5%-10% of women with post-menopausal bleeding are diagnosed with endometrial cancer. Current diagnostic techniques have limitations. Pipelle endometrial biopsy has a significant false-negative rate (10%-20%) and may fail to provide adequate diagnostic material in up to 30% of cases. Hysteroscopy, while useful, is associated with pain in up to 65% of patients and can delay diagnosis because of limited availability. Dilation and curettage is an invasive procedure requiring general anesthesia and has a higher complication rate. In response to these challenges, there is growing interest in developing new diagnostic tools that are less invasive and provide 1-step diagnoses, including liquid biopsies from urine, blood, cervico-vaginal and endometrial fluid samples by means of genomics and proteomics. This review will examine the current diagnostic algorithms in European and American guidelines, evaluate the sensitivity, specificity, and accuracy of current techniques, and explore new diagnostic tools under development.