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

Overview

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.

Interventions

• Procedure Sentinel Lymph Node Mapping
  The SLN mapping protocol will follow the EU guidelines and the consensus in competency assessment tool. Prior to SLN mapping, a full inspection of the pelvic areas with white light is performed to exclude the presence of extrauterine disease. The next surgical steps will be 1- identification of external iliac vessels, 2- identification of internal iliac artery, 3- dissection of the ureter, 4- development of paravesical space and 5- identification of obliterated umbilical ligament. The dissection
• Procedure Comprehensive pelvic and para-aortic lymphadenectomy
  The resection of at least one lymph node in each of the 12 retroperitoneal regions is necessary: A: upper para-aortic region B: lower para-aortic region C: interaorto-caval region D: paracaval region E: right and left iliaca communis region F: right and left iliaca externa region G: right and left fossa obturatoria region: defined by external and internal arteria iliaca, pelvic sidewall H: right and left iliaca interna region: lymph nodes adjacent to or medial of the internal iliacal artery

Primary outcome measures

• Disease-free-survival (DFS) [Time frame: 36 months]

Secondary outcome measures (8)

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

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

• Recurrent EC
• Previous chemo-, radio, or endocrine therapy for EC
• Any contra-indication to lymphadenectomy and/or chemotherapy
• Any contraindication to laparoscopy
• 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)
• Any known disorder or circumstances making participation in trial and follow-up questionable
• Patients with other malignancies for whom the disease(s) and/or associated treatment(s) might have an impact on the patient's cancer prognosis
• Known HIV-infection or AIDS
• Simultaneous participation in another interventional clinical trial
• Within the exclusion period following participation in another interventional clinical trial
• Patients with difficulties in reading or understanding French, or an inability to understand the delivered information
• Patients in emergency medical situations
• Patient under guardianship or limited guardianship

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Akladios C, Lecointre L, Lefebvre F, Eberst L, Menoux I, Ouldamer L, Lavoue V, Huchon C, Dabi Y, Gertych W, Guyon F, Laas E, Bonneau C, Kerbage Y, Chauleur C, Fauvet R, Brun JL, Raimond E, Gauthier T, Costaz H, Rouzier R, Hotton J, Marchal F, Loaec C, Ramanah R, Chopin N, Querleu D, Jochum F. Comparison of sentinel lymph node mapping with comprehensive lymphadenectomy in p53-mutated endometrial ca PMID 41796475

Identifiers

NCT: NCT06900582 · 9423

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗