Risk Stratification of Endometrial Cancer Patients: FIGO Stage, Biomarkers and Molecular Classification

Abstract

Endometrial cancer (EC) is the most common gynaecologic malignancy in developed countries. The main challenge in EC management is to correctly estimate the risk of metastases at diagnosis and the risk to develop recurrences in the future. Risk stratification determines the need for surgical staging and adjuvant treatment. Detection of occult, microscopic metastases upstages patients, provides important prognostic information and guides adjuvant treatment. The molecular classification subdivides EC into four prognostic subgroups: POLE ultramutated; mismatch repair deficient (MMRd); nonspecific molecular profile (NSMP); and TP53 mutated (p53abn). How surgical staging should be adjusted based on preoperative molecular profiling is currently unknown. Moreover, little is known whether and how other known prognostic biomarkers affect prognosis prediction independent of or in addition to these molecular subgroups. This review summarizes the factors incorporated in surgical staging (i.e., peritoneal washing, lymph node dissection, omentectomy and peritoneal biopsies), and its impact on prognosis and adjuvant treatment decisions in an era of molecular classification of EC. Moreover, the relation between FIGO stage and molecular classification is evaluated including the current gaps in knowledge and future perspectives.

Keywords: FIGO stage; ProMisE; TCGA; TRANSPORTEC; endometrial cancer; molecular classification; surgical staging; uterine neoplasm.

Figure 1

Surgically based FIGO staging system for endometrial cancer. Adapted from Cancer Research UK [CC-BY-SA-4.0] [32].

Figure 2

Relation between the traditional histologic classification and the molecular classification. Each traditional histologic diagnosis is connected to the molecular subgroup they represent. The thicker the connecting line, the stronger the relation. The figure demonstrates that each molecular classification is detected in each histologic subgroup, though NSMP is overrepresented amongst grade 1 and 2 EEC and p53abn cancers are most often diagnosed in patients with SC. EEC: endometrioid endometrial cancer, CCC: clear cell carcinoma, SC: serous cancer. NSMP: nonspecific molecular profile, MMRd: mismatch repair deficient, POLE: POLE ultramutated, p53abn: copy number high/TP53 mutated. Modified from UpToDate Endometrial cancer: Pathology and classification by Huvila J, MD, PhD, McAlpine JN, MD, FACOG, FRCPSC, available from: URL: https://www.uptodate.com/contents/endometrial-cancer-pathology-and-classification?source=history_widget (accessed on 10 November 2021).