A Retrospective Study on Multiple Classifier Endometrial Cancer

Multiple Classifier Endometrial Cancer

Endometrial cancer is not a single entity but rather a very heterogeneous group of diseases. Historically, endometrial cancer patients have been classified as endometrioid (type I) or non-endometrioid (type II) according to the dualistic Bokhman model- However, this approach has been limited in accurately predicting prognosis and guiding treatment owing to heterogeneity within subtypes, inadequate incorporation of molecular and genetic information, and high interobserver variability .

In the last ten years, after the publication of The Cancer Genome Atlas (TCGA)[5], the molecular classification of endometrial cancer into four molecular subtypes [(i) POLE/ultramutated group (POLE mutated), (ii) mismatch repair deficiency/microsatellite-instable, hypermutated group (MMRd/MSI-H), (iii) copy-number-high, TP53-mutant (CNH/p53abn), and (iv) copy-number-low, TP53-wild-type (CNL, or No Specific Mutational Profile [NSMP])] has rapidly gained interest. Recently, the European Societies of Gynaecological Oncology, Radiotherapy and Oncology, and Pathology (ESGO-ESTRO-ESP), the European Society of Medical Oncology (ESMO), the National Comprehensive Cancer Network (NCCN), and the new 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system have promoted the use of (surrogate) molecular classification. Retrospective studies supported the value of adopting molecular classification to offer reliable data on prognostication and adjuvant treatment decisions. Although no prospective data are available, current guidelines promote the use of molecular profiles to tailor adjuvant treatment after surgery. As only a few retrospective studies have investigated the association between molecular profiles and response to various adjuvant treatments, it is important to note that data are limited. Interestingly, the growing adoption of molecular profiling led to the detection of a subgroup of tumors called multiple classifiers, characterized by multiple (two or three) molecular features. According to the guidelines, tumors with a POLE mutation should be considered POLEmut, regardless of other molecular features, whereas MMRd/MSI-H tumors with a p53 abnormality should be considered MMRd/MSI-H. Data on these patients is limited and fragmentary. The aforementioned consensus is based solely on a large retrospective cohort of multiple classifiers collected by Leon-Castillo et al.. Hence, to fill this literature gap, the investigators designed this retrospective study, which aimed to collect multiple classifiers patients to improve knowledge on this emerging category.

Study Overview

• Status: Recruiting
• Conditions: Uterine Cancer
• Intervention / Treatment: Other: Observation only

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
    • Contact: Giorgio Bogani; Phone Number: 3803933116; Email: giorgiobogani@yahoo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a retrospective study with patients diagnosed with multiple classifier endometrial cancer Data of consecutive patients treated between June 1, 2019, and January 31, 2023, were collected.

Description

Inclusion criteria were the following: (i) histological diagnosis of endometrial cancer; (ii) execution of hysterectomy (with or without salpingo-oophorectomy) with or without nodal dissection; (iii) apparent early-stage disease; (iv) conventional pathological evaluation; and (v) molecular/genomic evaluation of the disease (including at least POLE sequencing, MMR protein immunostaining or MSI assessment, p53 immunostaining or TP53 sequencing). Exclusion criteria were: (i) consent withdrawal, (ii) execution of neoadjuvant therapy, and (iii) stage IV disease.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with multiple classifier endometrial cancer; Endometrial cancer patients who have two or more molecular features	Other: Observation only; Just obsrevation following standard of care (including surgery, chemotherapy and radiation when appropriate)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
progression-free survival	24 months

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2023
• Primary Completion (Estimated): August 31, 2023
• Study Completion (Estimated): August 31, 2023

Study Registration Dates

• First Submitted: July 27, 2023
• First Submitted That Met QC Criteria: July 27, 2023
• First Posted (Actual): August 4, 2023

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms; Uterine Neoplasms
• Other Study ID Numbers: 1402020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No