Sentinel Lymph Node Sampling for Patients With Middle-high Risk Endometrial Cancer Confined to the Uterus

Sentinel Lymph Node Sampling Versus Systematic Pelvic Lymphadenectomy on the Prognosis for Patients With Middle-high Risk Endometrial Cancer Confined to the Uterus Before Surgery: a Non-inferiority Randomized Controlled Trial

Aim To investigate the effect of sentinel lymph node (SLN) sampling on the prognosis of patients with middle-high risk endometrial cancer obviously confined to the uterus before surgery.

Study Overview

• Status: Recruiting
• Conditions: Prognosis; Middle-high Risk Endometrial Cancer; Sentinel Lymph Node Sampling
• Intervention / Treatment: Procedure: sentinel lymph node sampling (SLN); Procedure: pelvic lymphonodectomy (PLN)

Detailed Description

Aim to investigate the effect of sentinel lymph node (SLN) sampling on the prognosis of patients with middle-high risk endometrial cancer obviously confined to the uterus before surgery.

Rationale The diagnostic value of sentinel lymph node sampling has been widely approved. NCCN guideline suggested that "SLN mapping can be considered for the surgical staging of apparent uterine-confined malignancy when there is no metastasis demonstrated by imaging studies or no obvious extrauterine disease at exploration". However, the role of SLN in the prognosis of mid-high risk endometrial cancer clinically confined to the uterus is unclear. There are big concerns that SLN sampling only without lymph node dissection might miss isolated para-aortic lymph node metastasis or remain lymph node with metastasis other than SLN unremoved and thus affect the prognosis of patients. NCCN also suggested that "Para-aortic nodal evaluation from the inframesenteric and infraenal regions may also be utilized for staging in women with high-risk tumors such as deeply invasive lesions, high-grade histology, and tumors of serous carcinoma, clear cell carcinoma or carcinosarcoma. Thus, it is necessary to carry out a randomized trail to investigate the role of SLN in the prognosis of middle-high risk endometrial cancer obviously confined to the uterus before surgery.

Ethnics This study were approved by the Ethics Committees of Obstetrics and Gynecology Hospital of Fudan University and all other institutes. Before initiation of study procedures, written informed consent will be obtained from each patient regarding risks of treatments and agreement of using their clinical data for research purpose.

Randomization and Treatment This is a multicentered, open-label, randomized clinical trial. Randomization will be carried out in each center. A computer-based procedure of simple randomization (SPSS for Mac, version 22.0; IBM ) will be used for participant enrollment and randomization. Before an individual is successfully enrolled, her treatment assignment will remain concealed. This trial will be open label: patients and study physicians were aware of treatment assignment.

Eligible patients in each center will be randomly assigned (1:1) to receive:

1. Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus pelvic lymphonodectomy (PLN) with para-aortic sampling, or 2. Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus sentinel lymph node sampling (SLN).

1. The principles of surgery procedures and post-operative adjuvant therapies will follow the latest NCCN guidelines.
2. Surgery carried out by laparotomy, laparoscope, or robotic surgery are accepted.
3. Colored dyes including indocyanine green (ICG) (preferred), methylene blue, carbon nanotube for sentinel lymph node are accepted.
4. Postoperative adjuvant treatments are carried out following the latest NCCN guidelines according to doctors' choice.

Statistical analyses On the basis of data from previous studies (GOG249, FRACOGYN), the 2-year PFS is expected to be 88% in the PLN group and 87% in SLN group. SLN would be considered as inferior to PLN if the 2-year PFS in SLN group is higher than 80%. An accrual of 780 patients in 3 years will provide the study with adequate power (80%) to detect a clinically relevant absolute difference of 8% in 2-year PFS (88% vs 80%) between both groups (one-sided test, a=0.025), with a lost follow up rate ≤10% . Analyses will be done firstly by intention to treat.

• Study Type: Interventional
• Enrollment (Estimated): 780
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaojun Chen, Ph.D; Phone Number: 862163455050; Email: cxjlhjj@163.com
• Study Contact Backup: Name: Jun Guan, M.D; Phone Number: 862163455050; Email: junguan2018@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200011
      • Recruiting
      • Obstetrics and Gynecology Hospital, Fudan University
      • Contact: Xiaojun Chen, PhD; Phone Number: 862163455055; Email: cxjlhjj@163.com
      • Contact: Jun Guan, MD; Phone Number: 862163455055; Email: junguan2018@163.com
      • Principal Investigator: Xiaojun Chen, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Older than 18 years old;

2. Clinically diagnosed (by pre-surgical pathology and radiology) as primary endometrial cancer confined to uterus with middle-high risk factors:

   1. Disease limited to the uterus on image study (MRI, CT or ultrasound);
   2. including all histological types of endometrial cancer (endometrioid, serous, clear cell, carcinosarcoma, and undifferentiated carcinoma); not including uterine sarcoma
   3. excluding low-risk endometrial cancer (endometrioid G 1-2 with pre-surgical endometrial lesion≤2cm and myometrial invasion <50%);
   4. with one or more middle-high risk factors including: endometrioid endometrial cancer G3, myometrial invasion ≥50%, tumor size≥2cm, type II endometrial cancer; LVSI
   5. diagnosis should be confirmed by at least two senior clinicians.
3. Be able to undergo staging surgery.

Exclusion Criteria:

1. During pregnancy or perinatal period;
2. With malignancies other than endometrial cancer;
3. With history of important organs transplantation;
4. With immune diseases requiring taking immunosuppressants
5. With severe mental illness or brain function disorders
6. With history of drug abuse;
7. Allergic to contrast agent;
8. Still participating in other clinical trials;
9. Not willing to accept surgery or trial protocol;
10. Not eligible for surgery;
11. Had hysterectomy, chemotherapy, radiotherapy, or hormone therapy before the trail;
12. Had retroperitoneum lymph node dissection for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sentinel lymph node sampling; Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus sentinel lymph node sampling (SLN)	Procedure: sentinel lymph node sampling (SLN); Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus sentinel lymph node sampling (SLN).; The principles of surgery procedures and post-operative adjuvant therapies will follow the latest NCCN guidelines；; Surgery carried out by laparotomy, laparoscope, or robotic surgery are accepted；; Colored dyes including indocyanine green (ICG) (preferred), methylene blue, carbon nanotube for sentinel lymph node are accepted.
Active Comparator: Pelvic lymphadenectomy; Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus pelvic lymphonodectomy (PLN) with para-aortic sampling	Procedure: pelvic lymphonodectomy (PLN); Total hysterectomy with/without bilateral salpingooophorectomy (THBO) plus pelvic lymphonodectomy (PLN) with para-aortic sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The 2-year progression-free survival (2-year PFS)	The percentage of patients who have first relapse within 2 years after surgery (SLN or LND)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The 5-year PFS	The percentage of patients who have first relapse within 5 years after surgery (SLN or LND)	5 years
The 5-year overall survival (OS)	The percentage of patients who die within 5 years after surgery (SLN or LND)	5 years
Adverse effect and quality of life (QOL)	The occurence rate of each adverse effects related to surgery (SLN or LND, the scores of each QOL survay	Adverse effect: during the surgery, 30 days after surgery; QQL: 1 month before surgery, 6 months, 12 months after surgery

Collaborators and Investigators

• Sponsor: Xiaojun Chen
• Collaborators: Chongqing University Cancer Hospital; Sun Yat-sen University; Fudan University; Tongji Hospital; West China Second University Hospital

Publications and helpful links

General Publications

• Guan J, Xue Y, Zang RY, Liu JH, Zhu JQ, Zheng Y, Wang B, Wang HY, Chen XJ. Sentinel lymph Node mapping versus systematic pelvic lymphadenectomy on the prognosis for patients with intermediate-high-risk Endometrial Cancer confined to the uterus before surgery: trial protocol for a non-inferiority randomized controlled trial (SNEC trial). J Gynecol Oncol. 2021 Jul;32(4):e60. doi: 10.3802/jgo.2021.32.e60.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2020
• Primary Completion (Estimated): February 12, 2025
• Study Completion (Estimated): February 12, 2028

Study Registration Dates

• First Submitted: February 13, 2020
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (Actual): February 19, 2020

Study Record Updates

• Last Update Posted (Estimated): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Prognosis; Pelvic lymphadenectomy; Middle-high risk endometrial cancer; Sentinel lymph node sampling
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Endometrial Neoplasms
• Other Study ID Numbers: V01 2019-12

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No