Overview

This multicenter retrospective observational cohort study aims to evaluate the prognosis of patients with non-myoinvasive endometrial cancer harbouring high-risk molecular features by determining the rate of lymph node involvement (assessed by sentinel lymph node biopsy and/or lymphadenectomy), evaluating recurrence rates, progression-free survival (PFS) and overall survival (OS), and comparing oncological outcomes according to different adjuvant treatments.

The study will include patients with the following molecular subgroups of non-myoinvasive endometrial cancer:

• p53-abnormal tumours without myometrial invasion.
• High-grade NSMP tumours without myometrial invasion.
• ER-negative NSMP tumours without myometrial invasion.

Participating centres will be invited to retrospectively identify eligible patients diagnosed between 2010 and 2025 and enter anonymised data into a standardised REDCap database. Given the rarity of these clinical scenarios, international collaboration is essential to generate robust evidence that may help inform future clinical guidelines and optimize patient management.

Eligibility

Inclusion Criteria:

1. Patients over 18 years old.
2. Patients with:

   2.1. p53-abnormal (p53-abn) endometrial carcinoma. 2.2. ER-negative NSMP tumours. 2.3. High-grade NSMP tumours. POLE mutations assessment is not mandatory. MMR and p53 status is mandatory, according to ESGO criteria.

   In whom:

   • No myometrial invasion is present in the final surgical specimen (nor cervical or adnexal invasion).
   • Tumours are identified by endometrial biopsy or hysteroscopic polypectomy with no residual tumour in the final surgical specimen (these cases will also be considered tumours without myometrial invasion).
3. Patients who underwent nodal staging, either with pelvic sentinel lymph node biopsy, associated with pelvic and/or para-aortic lymphadenectomy, or staged by lymphadenectomy alone.

3.1. To assess the rate of lymph node involvement, we will analyze tumors with the previous molecular characteristics mentioned and no myometrial invasion, regardless of whether lymph node involvement is present. Stage IIIC tumours will not be excluded; cases will be selected based on the absence of myometrial infiltration in the final pathology specimen. 3.2. On the other hand, for the survival statistical analyses, only patients with a final stage IC (FIGO 2023) will be included.

Exclusion Criteria:

Patients who do not meet the above inclusion criteria and who additionally present with the following conditions will be excluded:

1. Molecular profile not available.
2. Absence of nodal staging (sentinel lymph node biopsy or lymphadenectomy)
3. Inadequate follow-up.
4. Mismatch repair-deficient tumors.
5. POLE-ultramutated tumors, when identified.
6. Incomplete information regarding adjuvant treatment.
7. Presence of myometrial invasion.