Further refining 2020ESGO/ESTRO/ESPmolecular risk classes in patients with early‐stage endometrial cancer: A propensity score–matched analysis

Abstract

BACKGROUND:The integration of molecular features with clinicopathological findings in endometrial cancer classification seems to be able to significantly refine risk assessment. Nevertheless, clinical management remains challenging, and different therapeutic options are available for each class. Further prognostic characterization of the subgroups within each risk class could be helpful in the decisionmaking process. METHODS: This study evaluated the role of the 2020 European Society of Gynaecological Oncology (ESGO)/European Society for Radiotherapy and Oncology (ESTRO)/European Society of Pathology (ESP) risk assessment system and the three prognostic profiles adopted in the PORTEC-4a trial in predicting disease-free and overall survival in a retrospective study cohort of patients with early-stage endometrial cancer. Patients were selected according to a 1:2 propensity score matching analysis. Moreover, the sequencing of 29 genes was undertaken for tumor samples. RESULTS: The study included 137 patients. No differences in disease-free or overall survival at 5 years were observed among the 2020 ESGO/ESTRO/ESP risk classes without molecular features (p = .766 and p = .176, respectively). Once molecular features were integrated, the probability of overall survival was significantly different (p = .011). When the three prognostic profiles were applied, the probability of recurrence had a p value of .097, and significant differences were observed in overall survival (p = .004). Among patients experiencing recurrence, 17.6% showed mutations in BRCA1/2, RAD50, BRIP1, and XRCC2, whereas 22.5% had PD-L1-positive expression and an MUTYH mutation. CONCLUSIONS: Further stratification within each risk class according to the most relevant prognostic features could better define the prognosis of patients with early-stage endometrial cancer. Nearly half of the patients who experienced recurrence showed a targetable molecular alteration for which dedicated trials should be encouraged.

Cancer statistics, 2023

“…91 The recent identification of distinct molecular subtypes offers opportunities for the development of targeted therapies, which could have a large impact because almost one half of early stage, recurrent endometrial cancers have targetable molecular alterations. 92,93 However, equitable dissemination of future advances will be critical to avoid exacerbating the current disparity, which is already one of the largest of all cancers. Stagnant survival trends for cervical cancer likely reflect in part an increased proportion of adenocarcinoma, which has poorer survival than squamous cell carcinoma, 94 because of the disproportionate detection of cervical intraepithelial neoplasia and early invasive squamous cell carcinoma during cytology screening.…”

“…Black women have the highest mortality rate of all racial and ethnic groups for every histologic subtype of uterine corpus cancer 91 . The recent identification of distinct molecular subtypes offers opportunities for the development of targeted therapies, which could have a large impact because almost one half of early stage, recurrent endometrial cancers have targetable molecular alterations 92,93 . However, equitable dissemination of future advances will be critical to avoid exacerbating the current disparity, which is already one of the largest of all cancers.…”

Outcomes and endpoints of relevance in gynecologic cancer clinical trials

“…In endometrial cancer, translational studies derived from the PORTEC trial biobank, incorporating comprehensive analysis of molecular factors, led to improved risk assessment of uterine carcinoma. 72 There are some potential roadblocks to completing translational endpoints that could be overcome by predefining them in the protocol, assuring an adequate and efficient sample management, even by central collection of pathologically reviewed samples, considering cost-benefit impact analyses, improving data sharing between different international research consortiums and, finally, increasing the involvement of patient advocates in the design of clinical trials.…”

Molecular classification in endometrial cancer: Opportunities for precision oncology in a changing landscape

“…It is within the context of molecular classification that Nero et al, 43 in this issue of Cancer , apply the PORTEC‐4a risk assignment stratification to a cohort of early‐stage (IA and IB) ECs both for prognostic stratification and to direct treatment. They further profile recurrent EC cases and identify potential therapeutic targets.…”