NCT04073706: ENDO-3

A Phase III Randomised Clinical Trial Comparing Sentinel Node Biopsy With No Retroperitoneal Node Dissection in Apparent Early-Stage Endometrial Cancer

Recruiting now Phase 3 Last updated 28 January 2026

What this trial tests

Phase 3 trial testing TH BSO with SNB Note: If participants (≤45yo), Grade 1 endometrial adenocarcinoma with myometrial invasion <50%, wish to retain their ovaries a BSO may be omitted in Endometrial Cancer Stage I in 760 participants. Currently enrolling.

Timeline

18 January 2021

Primary endpoint
1 January 2031

1 February 2031

Quick facts

Lead sponsor	Queensland Centre for Gynaecological Cancer
Phase	Phase 3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	760
Start date	18 January 2021
Primary completion	1 January 2031
Estimated completion	1 February 2031
Sites	19 locations across United States, Argentina, Australia, Brazil, Colombia, Italy, Singapore

Drugs / interventions tested

• TH BSO with SNB Note: If participants (≤45yo), Grade 1 endometrial adenocarcinoma with myometrial invasion <50%, wish to retain their ovaries a BSO may be omitted
• TH BSO without retroperitoneal node dissection Note: If participants (≤45yo), Grade 1 endometrial adenocarcinoma with myometrial invasion <50%, wish to retain their ovaries a BSO may be omitted

Conditions studied

• Endometrial Cancer Stage I — all drugs for Endometrial Cancer Stage I →
• Sentinel Lymph Node — all drugs for Sentinel Lymph Node →
• Surgery — all drugs for Surgery →

Sponsor

Queensland Centre for Gynaecological Cancer — full company profile →

Who can join

18 and older, female only, with Endometrial Cancer Stage I or Sentinel Lymph Node. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Stage 1: Return to usual activities
  Time frame: 12 months from surgery
  Proportion of participants returning to usual daily activities at 12 months from surgery using the EQ-5D which will determine when women in both groups can return to their usual activities.
• Stage 2: Disease Free Survival
  Time frame: 4.5 years from surgery
  Compare disease-free survival for participants randomised to receive hysterectomy, bilateral salpingo-oophorectomy with SNB compared to participants randomised to hysterectomy, bilateral salpingo-oophorectomy without retroperitoneal node dissection

Sponsor's own description

Endometrial cancer (EC) is the most common gynaecological cancer. Current treatment of EC typically includes removal of the uterus and to determine the extent of the disease (removal of fallopian tubes, ovaries \& if required a lymph node dissection (surgical staging)). While lymph node dissection may be valuable to guide the need for adjuvant treatment (chemo or radiotherapy) after surgery, it has been a topic of controversy for the last 30 years. In some patients it causes morbidity, specifically lymphoedema. This recently has been replaced with sentinel node biopsy (SNB). It requires an injection of a dye into the cervix with specific equipment \& surgical dissection of the lymph node in which the dye first becomes visible. Despite this promising proposition \& similar to a lymph node dissection, the value to patients, cost effectiveness \& potential harms (e.g. lymphedema) of SNB compared to no-node dissection in EC has never been established. Aim: determine the value of SNB for patients, the healthcare system and exclude detriment to patients using a randomised approach 1:1. Stage 1 - 444 patients. Stage 2 additional 316 patients.

Primary Outcome Stage 1:

Proportion of participants returning to usual daily activities at 12 months from surgery using the EQ-5D which will determine when women in both groups can return to their usual activities.

Primary Outcome Stage 2:

Treatment non-inferiority as evaluated by disease-free survival status at 4.5 years post-surgery, as measured by the time interval between the date of randomisation and date of first recurrence. Confirmation of recurrent disease will be ascertained through clinical assessment, radiological work-up and/or histological results.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. A phase III randomized clinical trial comparing sentinel node biopsy with no retroperitoneal node dissection in apparent early-stage endometrial cancer - ENDO-3: ANZGOG trial 1911/2020.
   Obermair A, Nicklin J, Gebski V, Hayes SC, et al · · 2021 · cited 39× · PMID 34728527 · DOI 10.1136/ijgc-2021-003029
2. Sentinel node biopsy for diagnosis of lymph node involvement in endometrial cancer.
   Nagar H, Wietek N, Goodall RJ, Hughes W, et al · · 2021 · cited 39× · PMID 34106467 · DOI 10.1002/14651858.cd013021.pub2
3. Paucity of data evaluating patient centred outcomes following sentinel lymph node dissection in endometrial cancer: A systematic review.
   Obermair HM, O'Hara M, Obermair A, Janda M. · · 2021 · cited 10× · PMID 33869716 · DOI 10.1016/j.gore.2021.100763
4. Sentinel Lymph Node Mapping in High-Grade Endometrial Cancer.
   Salman L, Cusimano MC, Marchocki Z, Ferguson SE. · · 2022 · cited 9× · PMID 35200595 · DOI 10.3390/curroncol29020096
5. The Sentinel Lymph Node in Treatment Planning: A Narrative Review of Lymph-Flow-Guided Radiotherapy.
   Ah-Thiane L, Rousseau C, Aumont M, Cailleteau A, et al · · 2023 · cited 2× · PMID 37345071 · DOI 10.3390/cancers15102736
6. Real-life utilization of sentinel lymph node mapping in endometrial cancer: Patterns of practice in unmapped patients and effect on treatment and outcomes.
   Glassman D, Kher R, Ananth CV, Girda E. · · 2025 · PMID 40511364 · DOI 10.1177/20503121251342047