Clinical trial NCT06900582: SENTInel Node Mapping Versus Comprehensive Lymphadenectomy in P53-Mutated Endometrial Cancer: a Non-Inferiority Randomized Trial
Official title: Comparing SENTInel Node Mapping to Comprehensive Lymphadenectomy in P53-Mutated EndoMETRial Cancer: a Prospective, Open-label, Controlled, Randomized, Non-inferiority, De-escalation Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Lymphadenectomy
Endometrial Cancer
Gene, P53
Sentinel Lymph Node Biopsy (SLNB)
Keywords: Endometrial cancer
Sentinel lymph node biopsy
Lymphadenectomy
p53 mutation
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2025-03-28
Enrollment: 374
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates surgical strategies for treating patients with FIGO 2023 stage I and II high-risk endometrial cancer (EC) exhibiting p53 mutations. The trial aims to assess whether a less invasive sentinel lymph node (SLN) mapping approach provides non-inferior oncological outcomes compared to the current standard of systematic pelvic and para-aortic lymphadenectomy (PL+PALND). By minimizing surgical morbidity, this study seeks to determine if SLN mapping can safely replace comprehensive lymphadenectomy without compromising disease-free survival (DFS). Eligible patients will be randomized to undergo either sentinel lymph node mapping or complete lymphadenectomy, followed by standard hysterectomy and bilateral salpingo-oophorectomy. The primary outcome is DFS at 36 months, with secondary outcomes including overall survival, disease-specific survival, perioperative complications, and quality of life.

Detailed description: The necessity of extensive lymph node dissection in endometrial cancer remains a subject of debate. Although systematic pelvic and para-aortic lymphadenectomy (PL+PALND) improves disease staging and influences adjuvant therapy, its impact on survival in high-risk endometrial cancer (EC) is still controversial. Recent evidence suggests that SLN mapping may provide comparable staging accuracy while reducing surgical complications. However, the oncological safety of replacing PL+PALND with SLN mapping in high-risk EC patients, particularly those with p53 mutations, remains uncertain.

This study is designed as a prospective, multicenter, randomized controlled trial to evaluate the non-inferiority of SLN mapping versus PL+PALND in patients with high-risk EC characterized by p53 mutations. Patients will be stratified based on tumor histology and imaging findings before undergoing surgery. The trial will enroll 374 patients across 22 participating centers.

Key issues addressed include:

* Oncological Safety: Assessing whether SLN mapping provides equivalent DFS compared to PL+PALND.
* Survival Outcomes: Evaluating overall survival (OS) and disease-specific survival (DSS) at 36 months.
* Surgical Morbidity: Comparing perioperative and postoperative complications
* Quality of Life: Determining patient-reported outcomes related to surgical recovery and long-term functional status.

This study integrates modern molecular classifications, recognizing p53 mutations as a significant prognostic marker. If SLN mapping is proven non-inferior, it could lead to a paradigm shift, reducing the extent of surgical intervention for high-risk EC patients while maintaining oncological safety.

Eligibility criteria: Inclusion Criteria:

1 . ≥ 18 years old 2. High-risk endometrial cancer, as defined by the ESGO-ESTRO 20211 histological and molecular classification, with p53 mutation confirmed on endometrial biopsy or curettage in the two months before the surgery 3. Magnetic Resonance Imaging (MRI) confirmed FIGO 2023 stage I and II endometrial cancer, i.e., confined to the uterine corpus, ovary and the cervical stroma.

4. Participant with a scheduled surgical intervention (total hysterectomy and bilateral salpingo-oophorectomy, with omentectomy in the case of serous, carcinosarcoma and undifferenciated type EC) 5. Eligible for comprehensive lymphadenectomy by laparoscopy 6. Participant with a negative Positron Emission Tomography scan (PET-CT scan) for lymph node involvement in the two months before the intervention 7. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1 8. Participant able to provide written informed consent

Exclusion Criteria:

1. Recurrent EC
2. Previous chemo-, radio, or endocrine therapy for EC
3. Any contra-indication to lymphadenectomy and/or chemotherapy
4. Any contraindication to laparoscopy
5. Any criteria, based on the investigator's judgment, that would contraindicate the surgical procedure (e.g., but not limited to, anesthetic risk, bleeding, significant comorbidities)
6. Any known disorder or circumstances making participation in trial and follow-up questionable
7. Patients with other malignancies for whom the disease(s) and/or associated treatment(s) might have an impact on the patient's cancer prognosis
8. Known HIV-infection or AIDS
9. Simultaneous participation in another interventional clinical trial
10. Within the exclusion period following participation in another interventional clinical trial
11. Patients with difficulties in reading or understanding French, or an inability to understand the delivered information
12. Patients in emergency medical situations
13. Patient under guardianship or limited guardianship

Primary outcomes:
measure: Disease-free-survival (DFS)
timeFrame: 36 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 36 months
measure: Disease-specific survival (DSS)
timeFrame: 36 Months
measure: Perioperative complications rate and postoperative complications rate
timeFrame: At 30- and 90-days
measure: Return to intended oncologic treatment (RIOT)
timeFrame: From the date of surgery (Day 0) until the first day of adjuvant treatment, assessed up to 90 days.
measure: Quality of life - EORTC QLQ-C30 questionnaire score
timeFrame: At baseline, 1, 6 and 12 months
measure: Quality of life - EORTC QLQ-EN24 questionnaire score
timeFrame: At baseline, 1, 6 and 12 months
measure: Accuracy of PET-CT scan in the detection of metastatic lymph nodes
timeFrame: From Day -60 to Day -1 before surgery (Day 0)
measure: Assessment of the rate of unsuccessful SLN mapping, requiring conversion to pelvic lymphadenectomy
timeFrame: At surgery time
Other outcomes:
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