A Retrospective Study on Multiple Classifier Endometrial Cancer

Uterine Cancer Clinical Trial

Official title:

Multiple Classifier Endometrial Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05976113
• Other study ID #: 1402020
• Status: Recruiting
• Start date: July 27, 2023
• Est. completion date: August 31, 2023

Study information

• Verified date: July 2023
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Endometrial Neoplasms
• Uterine Cancer
• Uterine Neoplasms

Intervention

Other:
• Observation only
Just obsrevation following standard of care (including surgery, chemotherapy and radiation when appropriate)

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival		24 months