Comparison of Molecular and Clinicopathologic-Based Classifications and the Transition of Adjuvant Treatment Mode for Early-Stage Endometrial Cancer

Abstract

Due to the division in classification strategies based on different molecular and clinicopathologic guidelines, the current emergence of multiple molecular typing methods greatly challenges the traditional classification-guided hierarchical treatment model. The early-stage ECs who underwent a total hysterectomy and comprehensive molecular analyses were analyzed consecutively between May 2021 and December 2022. All enrolled patients were performed with immunohistochemistry for lymph-vascular space invasion (LVSI), p53, and mismatch repair (MMR) proteins, NGS-panel Sanger sequencing for POLE exonuclease domain, and TP53. The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) classifier and the ESGO/ESTRO/ESP guidelines with and without molecular character were respectively employed to reclassify the enrolled patients. Categorical variables of the risk-group shift were compared by Pearson's χ2 or two-sided Fisher's exact test. A total of 81 early-stage ECs patients were enrolled. Molecular analyses identified four subgroups across the 81 ECs: 9 (11%) POLE mut, 22 (27.1%) MMRd, 38 (46.9%) NSMP, and 12 (14.8%) p53 abn. Compared with ESGO/ESTRO/ESP 2016 classifier, 26 (32.1%) and 23 (28.4%) patients in ESGO/ESTRO/ESP 2020 cohort with and without molecular classification, respectively, were risk-group downshifted (p>0.05). Ten (12.3%) patients were upshifted in ESGO/ESTRO/ESP 2020 molecular classification comparing to clinical classifier. Remarkably, two patients demonstrated discordance between the ProMisE and TCGA classifiers since the different sequences of classification strategies. On the other hand, 48 of 81 patients received adjuvant radiotherapy, and 12 patients received external beam radiation therapy (EBRT). According to the final molecular test, eight of 12 were classified into low and intermediate risk. The treatment of endometrial cancer is in a period of transition from the clinicopathologic-based model to the era of molecular precision. Discordance between different classifiers and overtreatment remain in clinical practice. Therefore, we should be cautious about using molecular typing to guide adjuvant treatment decisions until it is finally validated in prospective trials.