Comparison Between High and Low Level Para-aortic Lymphadenectomy in High and Intermediate Risk Endometrial Carcinoma

Endometrial cancer (EC) is the most frequent gynecological malignancy in developed countries and ranks second in incidence worldwide after cervical cancer, accounting for nearly 10% of cancers in women . With the adoption of comprehensive surgical staging, the identification of extra-uterine disease has become central to treatment and prognosis. Lymph node involvement, particularly para-aortic nodal metastasis, represents one of the most important independent prognostic factors .

The uterus has a complex lymphatic drainage, with pathways leading to the obturator, iliac, caval, aortic, parametrial, and presacral basins. Direct channels from the uterine fundus to the para-aortic nodes via the infundibulopelvic ligament explain metastatic spread to the para-aortic region, although isolated para-aortic involvement in the absence of pelvic nodal disease is uncommon. Recognition of these drainage patterns underscores the importance of evaluating both pelvic and para-aortic lymph nodes in high- and intermediate-risk patients .

Several studies suggest that systematic lymphadenectomy, including the para-aortic region, improves survival by enhancing staging accuracy and guiding adjuvant therapy. Combined pelvic and para-aortic lymphadenectomy (PALD) has been associated with increased 5-year overall survival, improved disease-free survival, reduced recurrence, and decreased need for adjuvant radiotherapy . However, the optimal extent of para-aortic dissection remains debated. Para-aortic nodes are subdivided relative to the inferior mesenteric artery (IMA) into inframesenteric (low-level) and supramesenteric (high-level). While high-level PALD may improve detection of occult metastases, it increases surgical complexity and morbidity .

Risk stratification of EC guides the extent of staging. High-risk disease includes non-endometrioid histologies, grade 3 endometrioid carcinoma with >50% myometrial invasion, and advanced local spread. Intermediate-risk disease encompasses grade 1-2 tumors with deep or larger-volume myometrial invasion. Patients in these categories have a significant risk of nodal involvement (up to 16%), warranting para-aortic evaluation .

The present study aims to compare high versus low PALD in intermediate- and high-risk EC with emphasis on nodal yield, histopathological characteristics, staging, and oncological outcomes.

Study Overview

• Status: Completed
• Conditions: Endometrial Cancer
• Intervention / Treatment: Procedure: high level para-aortic lymphadenectomy; Procedure: low level para-aortic lymphadenectomy

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Kafr ash Shaykh, Egypt
    • Kafr Elsheikh University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The inclusion criteria consisted of women diagnosed with either intermediate- or high-risk EC, based on established pathological and radiological criteria. •Intermediate-risk patients included those with grade 1/2 endometrioid carcinoma with <50% myometrial invasion and tumor size >2 cm, grade 1/2 with 50-66% invasion, or grade 3 with <50% invasion.

  • High-risk cases were defined as non-endometrioid histology (serous or clear cell), grade 1 or 2 endometrioid carcinoma with more than 66% invasion, grade 3 with more than 50% invasion, or the presence of adnexal metastasis.

Exclusion Criteria:

• Patients were excluded if they had general contraindications to surgery, morbid obesity that precluded safe operative access, or if they declined to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: group A high; underwent high-level PALD, where lymphatic dissection was extended above the IMA up to the left renal vein.	Procedure: high level para-aortic lymphadenectomy; All women underwent total hysterectomy with bilateral salpingo-oophorectomy combined with systematic pelvic lymphadenectomy and high-level PALD was done .The small bowel and mesentery were carefully mobilized to expose the aorta and inferior vena cava (IVC) above the IMA, with dissection proceeding cranially to the left renal vein. The anatomical landmarks were consistently identified to ensure complete lymphatic clearance within the defined field. Excised lymph nodes were counted intraoperatively and verified by histopathology.
Active Comparator: group B low; underwent low-level PALD, in which lymph node dissection was confined to the infra-mesenteric region, extending from the aortic bifurcation to just below the IMA.	Procedure: low level para-aortic lymphadenectomy; All women underwent total hysterectomy with bilateral salpingo-oophorectomy combined with systematic pelvic lymphadenectomy and high-level PALD was done .The small bowel and mesentery were carefully mobilized to expose the aorta and inferior vena cava (IVC) , the dissection was restricted to the infra-mesenteric region between the aortic bifurcation and the IMA. The anatomical landmarks were consistently identified to ensure complete lymphatic clearance within the defined field. Excised lymph nodes were counted intraoperatively and verified by histopathology.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
descriptive operative outcome	The primary surgical outcome is para-aortic nodal yield how to measure paraaortic LN Yeild : surgical removal and pathological analysis, focusing on the number of nodes harvested (total yield) and the number of positive nodes (involved yield) relative to total nodes.	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
survival outcome	Long-term oncological outcome, including (Overall survival) survival status at follow-up (alive, deceased, or lost to follow-up).	1 year

Collaborators and Investigators

• Sponsor: Ahmed Aouf

Publications and helpful links

General Publications

• Somashekhar, S. P. et al. Prospective Non-randomized Control Trial on Role of Systematic High Para-Aortic Lymphadenectomy in Endometrial Cancer: Indian Study. Indian J Gynecol Oncolog 19, 6 (2021). 2. Jung, U. S., Choi, J. S., Bae, J., Lee, W. M. & Eom, J. M. Systemic Laparoscopic Para-Aortic Lymphadenectomy to the Left Renal Vein. JSLS 23, e2018.00110 (2019). 3. El-Agwany, A. S. & Meleis, M. H. Value and best way for detection of Sentinel lymph node in early stage endometrial cancer: Selective lymphadenectomy algorithm. European Journal of Obstetrics & Gynecology and Reproductive Biology 225, 35-39 (2018). 4. Petousis, S. et al. Combined pelvic and para-aortic is superior to only pelvic lymphadenectomy in intermediate and high-risk endometrial cancer: a systematic review and meta-analysis. Arch Gynecol Obstet 302, 249-263 (2020). 5. AlHilli, M. M. & Mariani, A. The role of para-aortic lymphadenectomy in endometrial cancer. Int J Clin Oncol 18, 193-199 (2013). 6. Zammarrelli, W. A. et al. Risk Stratification of Stage I Grade 3 Endometrioid Endometrial Carcinoma in the Era of Molecular Classification. JCO Precis Oncol e2200194 (2022) doi:10.1200/PO.22.00194. 7. Yang, Y., Wu, S. F. & Bao, W. Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies. International Journal of Gynecology & Obstetrics 164, 436-459 (2024). 8. Thammineedi, S. R., Iyer, R. R., Naren, B. & Patnaik, S. C. Lymphadenectomy in Endometrial Cancers-A Review. Indian J Gynecol Oncolog 19, 77 (2021). 9. AlHilli, M. M. et al. Preoperative biopsy and intraoperative tumor diameter predict lymph node dissemination in endometrial cancer. Gynecologic Oncology 128, 294-299 (2013). 10. Hashmi, A. A. et al. Morphological Spectrum and Pathological Parameters of Type 2 Endometrial Carcinoma: A Comparison With Type 1 Endometrial Cancers. Cureus 12, (2020). 11. Song, S.-H. et al. Clinicopathologic Characteristics and Prognostic Factors of Stage I and II Endometrial cancer of the uter

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): May 1, 2025

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 26, 2025
• First Posted (Actual): December 29, 2025

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 26, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Endometrial Cancer; hystrectomy; para-aortic lymphadenectomy; high level para-aortic lymphadenectomy; low level para-aortic lymphadenectomy; survival outcome
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms
• Other Study ID Numbers: KFSIRB200-762

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: there is a plan to make IPD available. It also means that a data dictionary (a description of the variables, or types of data, collected for each individual) will be provided so that the data can be fully interprete
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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