Implementation of the 2021 molecular ESGO/ESTRO/ESP risk groups in endometrial cancer

This was a retrospective study of 604 patients with endometrial carcinoma, classified into ESGO-ESTRO-ESP 2021 clinicopathologic and molecular integrated risk groups. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) and Leiden classifier were employed for molecular classification. Median follow-up time was 81 months. Clinicopathologic and molecular integrated risk groups were similarly associated with distinct prognoses (p < 0.001). Disease-specific survival was similar for all molecular subgroups within clinicopathologic intermediate-risk, high-risk, and advanced/metastatic groups. In contrast, the p53 abnormal subgroup (hazard ratio 9.1, 95% confidence interval 2.0–41; p = 0.004) and mismatch repair deficient subgroup (hazard ratio 3.5, 95% confidence interval 1.2–10; p = 0.024) were associated with disease-related death within clinicopathologic low-risk and high-intermediate-risk carcinomas, respectively. A risk-group shift occurred in 6.0% (36/604) and 7.4% (38/515) of patients classified by ProMisE and Leiden, respectively (p = 0.341). Of the 36 patients shifted in the ProMisE cohort, 27 were upshifted and 9 downshifted. Based on the Leiden classifier, polymerase-ϵ sequencing could be omitted in 60% (311/515) of patients without affecting the risk-group assessment. ESGO-ESTRO-ESP 2021 guidelines provide a platform for risk classification in future trials on molecularly directed treatment of endometrial carcinoma.

Section: Discussionmentioning

confidence: 95%

Clinicopathologic vs. Molecular Integrated Prognostication of Endometrial Carcinoma by European Guidelines

Loukovaara

Pasanen

Bützow

2022

“…Carcinosarcomas mainly fall into the p53abn group and might have a worse prognosis than serous EC in the p53abn group. Whether combining information on histotype with the molecular subgroup could improve prognosis prediction is under study [ 74 , 75 ].…”

Section: Molecular Risk Classificationmentioning

confidence: 99%

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

Kasius¹,

Pijnenborg

Lindemann

et al. 2021

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.

“…In this study, we have provided one of the first evaluations of this new risk classification in a cohort of patients and, to our knowledge, the first comparison of the three classifiers focused on early-stage EC. Two recent publications have evaluated the 2020 Classifier in two large patient cohorts, including those with advanced disease [ 32 , 33 ]. Similar to our results, Ortoft et al described fewer patients allocated to the high-risk group using the 2020 Classifier and reported a poorer RFS for this group than that achieved with the 2016 Classifier [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Prognosis Stratification Tools in Early-Stage Endometrial Cancer: Could We Improve Their Accuracy?

Ramon-Patino

Ruz-Caracuel

Heredia-Soto

et al. 2022

There are three prognostic stratification tools used for endometrial cancer: ESMO-ESGO-ESTRO 2016, ProMisE, and ESGO-ESTRO-ESP 2020. However, these methods are not sufficiently accurate to address prognosis. The aim of this study was to investigate whether the integration of molecular classification and other biomarkers could be used to improve the prognosis stratification in early-stage endometrial cancer. Relapse-free and overall survival of each classifier were analyzed, and the c-index was employed to assess accuracy. Other biomarkers were explored to improve the precision of risk classifiers. We analyzed 293 patients. A comparison between the three classifiers showed an improved accuracy in ESGO-ESTRO-ESP 2020 when RFS was evaluated (c-index = 0.78), although we did not find broad differences between intermediate prognostic groups. Prognosis of these patients was better stratified with the incorporation of CTNNB1 status to the 2020 classifier (c-index 0.81), with statistically significant and clinically relevant differences in 5-year RFS: 93.9% for low risk, 79.1% for intermediate merged group/CTNNB1 wild type, and 42.7% for high risk (including patients with CTNNB1 mutation). The incorporation of molecular classification in risk stratification resulted in better discriminatory capability, which could be improved even further with the addition of CTNNB1 mutational evaluation.