Comparison of sentinel lymph node mapping with comprehensive lymphadenectomy in p53-mutated endometrial cancer: a prospective, multi-center, non-inferiority, open-label, de-escalation, randomized, controlled trial (Study Protocol - SENTIMETREP53).

BACKGROUND

The therapeutic value of lymphadenectomy in endometrial cancer remains controversial, particularly in high-risk patients as defined by the European Society of Gynaecological Oncology-European Society for Radiotherapy and Oncology 2021 histologic and molecular classification. While pelvic and para-aortic lymphadenectomy is the standard of care for high-risk endometrial cancer, sentinel lymph node (SLN) mapping has emerged as a promising alternative for low-risk patients with reduced post-operative morbidity. Recently, the advent of molecular classification has significantly influenced the diagnosis and management of endometrial cancer. In particular, p53 mutation has been recognized as an important prognostic marker and has been included in the criteria for high-risk classification.

PRIMARY

OBJECTIVE

To evaluate the impact of SLN mapping versus pelvic and para-aortic lymphadenectomy on disease-free survival at 3 years in high-risk patients with endometrial cancer with p53 mutation and a negative pre-operative positron emission tomography computed tomography scan.

STUDY HYPOTHESIS: SLN mapping will provide non-inferior survival outcomes compared with pelvic and para-aortic lymphadenectomy in this population, with reduced post-operative morbidity.

TRIAL

DESIGN

This is a prospective, multicentre, non-inferiority, open-label, de-escalation, randomized, controlled trial in patients with International Federation of Gynecology and Obstetrics 2023 stage I and II endometrial cancer with p53 mutation and negative pre-operative positron emission tomography computed tomography scans. Patients will be randomized 1:1 to SLN mapping or pelvic and para-aortic lymphadenectomy.

MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible participants are aged ≥18 years, with International Federation of Gynecology and Obstetrics 2023 stage I or II endometrial cancer confirmed by magnetic resonance imaging, a p53 mutation verified by biopsy, and planned surgery including total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy if indicated. Exclusion criteria include recurrent endometrial cancer, prior chemotherapy, radiotherapy, endocrine therapy, or contraindications to lymphadenectomy or laparoscopy.

PRIMARY ENDPOINT: Disease-free survival at 36 months.

SAMPLE SIZE: A total of 374 patients.

ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING

RESULTS

Estimated completion of recruitment in September 2028, with 36 months of follow-up completed by September 2031.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06900582.