Lymphedema After Primary Surgery for Endometrial Cancer (LASEC)

Prevalence, Complications and Risk Factors for Lymphedema After Pelvic and Paraaortic Lymphadenectomy in Primary Radical Surgery for Early Stage Endometrial Carcinoma.

The purposes of this study are

• to determine the prevalence, size and impact on quality of life of lymphedema of the lower extremities after primary radical surgery with hysterectomy +/- pelvic - and paraaortic lymphadenectomy in women with endometrial uterine carcinoma FIGO (International Federation of Gynecology and Obstetrics) stage 1 and 2
• to analyze risk factors for development of lymphedema in this specific group of patients.

Our hypotheses are that women who have lymphadenectomy more often suffer from lymphedema, subjectively and objectively, and have an impaired quality of life.

This is a Swedish multicenter study carried out in 17 departments of Obstetrics and Gynecology and in 3 departments of Oncology. All participants are treated according to the Swedish National Guidelines for Endometrial Cancer.

130 women with endometrial cancer who have a hysterectomy with lymphadenectomy (high-risk endometrial carcinomas) and 130 women with endometrial cancer who have a hysterectomy without lymphadenectomy (low-risk endometrial carcinomas) are prospectively enrolled in the study.

The participants are examined preoperatively and on 3 occasions postoperatively, i.e. 4-6 weeks , 6 months and 12 months postoperatively.

Determination of occurrence of lymphedema of the lower extremities are determined objectively by 1) a standardized clinical evaluation according to Bruna et al.[1] and 2) determining the leg volume according to the cone model by Sitzia [2] by systematically measuring of leg circumferences. In addition, occurrence of lymphedema is measured subjectively by the participants.

On the same four occasions as the leg circumference measurements are conducted the patients complete two generic health related quality of life forms (the EuroQol EQ-5D and the Short-Form 36 SF-36) and the condition specific quality of life form for limb lymphedema (LYMQOL).

Demographic and clinical data are systematically collected until one year postoperatively including occurrence of complications and given adjuvant oncological therapy such as chemo- and radiation therapy.

On each occasion of clinical control a vaginal ultrasound examination is carried out in order to register pelvic and abdominal lymphocele formation or lymphatic fluid effusion intraabdominally.

Study Overview

• Status: Completed
• Conditions: Hysterectomy; Lymphadenectomy; Carcinoma of the Endometrium
• Intervention / Treatment: Procedure: Lymphadenectomy

Detailed Description

Not included

• Study Type: Observational
• Enrollment (Actual): 262

Contacts and Locations

Study Locations

• Sweden
  • Falun, Sweden, 79182
    • Falu Central Hospital
  • Gävle, Sweden, 80187
    • Gävle County Hospital
  • Göteborg, Sweden, 41345
    • Sahlgrenska University Hospital
  • Halmstad, Sweden, 30233
    • Region Halland Halmstad Hospital
  • Kalmar, Sweden, 39185
    • County Hospital in Kalmar
  • Karlskrona, Sweden, 37185
    • Blekinge hospital
  • Karlstad, Sweden, 65185
    • Karlstad Central Hospital
  • Linkoping, Sweden, 58185
    • Linkoping University Hospital
  • Skövde, Sweden, +4651085000
    • Södra Älvborgs Sjukhus
  • Sundsvall, Sweden, 85186
    • Sundsvall Hospital
  • Trollhättan, Sweden, 46185
    • Norra Älvborgs Hospital
  • Umeå, Sweden, 90185
    • Norrlands University Hospital
  • Uppsala, Sweden, 75185
    • Akademiska University Hospital
  • Varberg, Sweden, 43281
    • Region Halland Varberg hospital
  • Västervik, Sweden, 59381
    • Västervik County Hospital
  • Jonkopings Län
    • Eksjo, Jonkopings Län, Sweden, 57533
      • Highland Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

All women admitted to the participating clinics for primary surgery of endometrial carcinoma FIGO stage 1 and 2 will be asked to participate in the study.

Description

Inclusion Criteria:

• Age >=18 years.
• Women with endometrial carcinoma preoperatively evaluated to be uterine cancer FIGO stage1 or 2 who are planned for primary radical surgery including simple or radical hysterectomy, bilateral salpingoophorectomy,+/- pelvic and paraaortic lymphadenectomy and +/- omentectomy with curative intention.
• WHO performance status ≤ 2.
• Understand and speak Swedish fluently
• Accept to participate in the study by giving verbal and written informed consent.

Exclusion Criteria:

• Sarcoma of the uterus
• Previous pelvic or paraaortic lymphadenectomy.
• Previous having had pelvic radiation therapy.
• Ongoing treatment of arterial or venous insufficiency of the lower limbs
• Congenital or acquired malformations in the lymphatic system.
• Ongoing or previous treatment of lymphedema of the upper or lower limbs.
• Physically disability which impair mobilisation immediately postoperatively.
• Severe psychiatric disease and untreated mild/moderate psychiatric disease.
• Mentally retarded to a degree so she does not understand the meaning of the participation or cannot fill in the questionnaires.or the physician finds it ethically doubtful to enroll the patient in the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group with lymphadenectomy; The group of women with high risk endometrial cancer who undergoes pelvic and/or paraaortic lymphadenectomy at primary surgery	Procedure: Lymphadenectomy; Pelvic and/or paraaortic lymphadenectomy
Group without lymphadenectomy; The group of women with low risk endometrial cancer who do not have lymphadenectomy at primary surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in leg volume from baseline (preoperatively) to 4-6 weeks postoperatively	Leg volume is determined by the cone model according to Sitzia by measuring leg circumferences systematically.	4-6 weeks after the primary surgery
Change in leg volume from baseline (preoperatively) to 6 months postoperatively	Leg volume is determined by the cone model according to Sitzia by measuring leg circumferences systematically.	6 months after the primary surgery
Change in leg volume from baseline (preoperatively) to 12 months postoperatively	Leg volume is determined by the cone model according to Sitzia by measuring leg circumferences systematically.	12 months after the primary surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quality of life assessment from baseline (preoperatively) to 4-6 weeks postoperatively	Quality of life measured by means of The EuroQol (EQ-5D), the Short-Form 36 (SF-36) and the condition specific quality of life form LYMQOL.	4-6 weeks from the primary surgery
Change in quality of life assessment from baseline (preoperatively) to 6 months postoperatively	Quality of life measured by means of The EuroQol (EQ-5D), the Short-Form 36 (SF-36) and the condition specific quality of life form LYMQOL.	6 months from the primary surgery
Change in quality of life assessment from baseline (preoperatively) to 12 months postoperatively	Quality of life measured by means of The EuroQol (EQ-5D), the Short-Form 36 (SF-36) and the condition specific quality of life form LYMQOL.	12 months from the primary surgery
Percentage of participants with an increase in leg volume of > 15% 12 months postoperatively		12 months after the primary surgery
Percentage of participants who states they have lymphedema	Occurrence of lymphedema subjectively graded as 2 or more on an ordinal scale from 1 to 4. 1 express no swelling of the legs and 4 express severe swelling.	12 months from the primary surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk factors for lymphedema after primary surgery with lymphadenectomy for endometrial cancer	Risk factors defined in terms of number of lymphnodes removed, site of lymphnodes, peri- and postoperative complications, adjuvant chemotherapy, adjuvant radiation therapy, age, histopathological subtype, surgical FIGO stage, DNA-ploidy status of the tumor, comorbidity and relapse of the cancer.	Within 12 months after the surgery

Collaborators and Investigators

• Sponsor: Preben Kjolhede, MD, professor
• Collaborators: Linkoeping University; Ostergotland County Council, Sweden; Medical Research Council of Southeast Sweden; Swedish Cancer Society
• Investigators: Study Chair: Preben Kjölhede, MD, PhD, Dept of Obs/Gyn, University Hospital, Linköping; Study Chair: Per Rosenberg, MD,PhD, Dept of Oncology, University Hospital, Linköping; Study Chair: Gabriel Lindahl, MD, Dept of Oncology, University Hospital, Linköping; Study Chair: Eva Ahlner, RPT, Dept of Oncology, University Hospital, Linköping; Study Chair: Janusz Marcickiewicz, MD, PhD, Dept of Obs/Gyn, Region Halland Varberg Hospital, Varberg; Study Chair: Karin Stålberg, MD, PhD, Dept of Obs/Gyn, Univeristy Hospital, Uppsala; Principal Investigator: Ulrika Ottander, MD, PhD, Dept of Obs/Gyn, Norrlands University Hospital, Umeå; Principal Investigator: Kristina Aglund, MD, PhD, Dept of Oncology, Norrlands University Hospital, Umeå; Principal Investigator: Åsa Åkesson, MD, PhD, Dept of Obs/Gyn, Sahlgrenska University Hospital, Göteborg; Principal Investigator: Eva Blank, MD, PhD, Dept of Obs/Gyn, Norra Älvsborg County Hospital in Trollhättan, Trollhättan; Principal Investigator: Lars Högström, MD, PhD, Dept of Obs/Gyn, Södra Älvsborgs Hospital, Borås; Principal Investigator: Eva Rundqvist, MD, Dept of Obs/Gyn, Blekinge Hospital, Karlskrona; Principal Investigator: Margareta Lood, MD, Dept of Obs/Gyn, Central Hospital, Karlstad; Principal Investigator: Lotta Andreen, MD, PhD, Dept of Obs/Gyn, Central Hospital, Sundsvall; Principal Investigator: Peter Smith, MD, PhD, Dept of Obs/Gyn, Central Hospital, Gävle; Principal Investigator: Åsa Nyberg, MD, PhD, Dept of Obs/Gyn, Central Hospital, Falun; Principal Investigator: Lisbeth Liest, MD, Dept of Obs/Gyn, Highland Hospital, Eksjö; Principal Investigator: Gunnel Lindell, MD, PhD, Dept of Obs/Gyn, Kalmar County Hospital, Kalmar; Principal Investigator: Anders Rosenmüller, MD, Dept of Obs/Gyn, Västervik County Hospital, Västervik

Publications and helpful links

General Publications

• Miller AJ, Bruna J, Beninson J. A universally applicable clinical classification of lymphedema. Angiology. 1999 Mar;50(3):189-92. doi: 10.1177/000331979905000302.
• Sitzia J. Volume measurement in lymphoedema treatment: examination of formulae. Eur J Cancer Care (Engl). 1995 Mar;4(1):11-6. doi: 10.1111/j.1365-2354.1995.tb00047.x.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2014
• Primary Completion (Actual): December 17, 2018
• Study Completion (Actual): December 17, 2018

Study Registration Dates

• First Submitted: April 13, 2014
• First Submitted That Met QC Criteria: April 13, 2014
• First Posted (Estimate): April 16, 2014

Study Record Updates

• Last Update Posted (Actual): October 25, 2019
• Last Update Submitted That Met QC Criteria: October 24, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Lymphedema; Lymphadenectomy; Hysterectomy; Uterus cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Lymphatic Diseases; Neoplasms, Glandular and Epithelial; Lymphedema; Carcinoma
• Other Study ID Numbers: Version 2013-09-22/2014-03-21; The Swedish Cancer Society (Other Grant/Funding Number: CAN 2013/620)