# Alignment of Molecular Classification Between Diagnosis and Recurrence in Endometrial Cancer: Lessons from a Single-Institution Experience to Inform Future Pathways

## TL;DR

This study examines how the molecular classification of endometrial cancer changes from diagnosis to recurrence, offering insights for future treatment strategies.

## Contribution

The study is the first to focus on molecular classification discordance in endometrial cancer relapses compared to initial diagnosis.

## Key findings

- Out of 221 cases, 18 recurrences were found with only two showing molecular classification changes.
- The discordance rate was not statistically significant but highlights the need for further research.
- The findings suggest potential evolution in molecular profiles, warranting larger studies.

## Abstract

Endometrial cancer treatment and prognosis have greatly improved thanks to advances in understanding its molecular profile. However, it is still unclear whether these molecular characteristics remain stable over time, particularly when the disease returns after initial treatment. This study explores the concordance and potential evolution of molecular classification between primary diagnosis and recurrence in endometrial cancer, building upon emerging evidence that has begun to address this question. This study explores the concordance and potential evolution of molecular classification between primary diagnosis and recurrence in endometrial cancer, building upon emerging evidence that has begun to address this question. By examining this relationship, our research provides valuable preliminary data that could guide future studies on the biological behavior of recurrent disease. These insights may ultimately contribute to more precise and personalized treatment strategies for patients with endometrial cancer.

Introduction: Endometrial carcinoma (EC) is the most prevalent gynecological cancer. It is characterized by a clinical, pathological, and prognostic trajectory that has become inextricably linked to the disease’s molecular profile. Therefore, it is imperative to examine its relevance across all facets associated with the disease. Methods: This is a single-center retrospective study to assess tumor molecular profile concordance between EC diagnosis and recurrence. All patients who underwent hysterectomy for EC between 2016 and 2020 were included. Results: In total, 221 cases of EC were collected. In total, 18 recurrences were found. In two cases, there was a molecular classification (MC) change: an MMR-deficient endometrioid EC shifted to a “multiple classifier” subtype. The second, an NSMP subtype, at second recurrence revealed a switched MC to an aberrant mutated p53 profile. This discordance rate was non-significant in our cohort. However, considering the lack of evidence, it opens new insights to be revealed. Conclusions: This is the first study focusing on the discordance rate of MCs in EC relapses compared to the initial diagnosis. Future large-scale retrospective and prospective multicenter studies are essential for exploring this aspect.