On lymphedema of the lower limbs after treatment of endometrial cancer : with emphasis on incidence, quality of life, risk factors, and health economy

Abstract: Objectives: The overall purpose of this study was to investigate the long-term consequences of primary surgical treatment of endometrial cancer with emphasis on lymphadenectomy, lymphedema development in the limbs, health-related quality of life, and health economy aspects. The primary objective was to assess the incidence of lymphedema both objectively and subjectively by using three different methods to determine lymphedema. Secondary objectives were to determine risk factors for lymphedema, and to analyze the impact of lymphadenectomy and lymphedema on health-related quality of life. Another secondary objective was to evaluate the hospital costs of lymphadenectomy and lymphedema one year after primary treatment of endometrial cancer.Material and methods: The study was a prospective observational longitudinal multicenter study with 15 Swedish hospitals participating between June 2014 and January 2018. Two hundred sixty-two women with presumed early stage endometrial cancer were included; 235 women completed the study. Of these, 119 were classified as having high-risk endometrial cancer and underwent surgery including lymphadenectomy, and 116 were classified as having low-risk endometrial cancer where no lymphadenectomy was performed. The women were evaluated preoperatively according to the national guidelines for endometrial cancer. The women were all monitored on four occasions: preoperatively, then four to six weeks, six months, and one year postoperatively. On all occasions, lymphedema was evaluated by means of two objective methods: systematic circumferential measurements of the lower limbs, enabling estimation of the leg volume, and by clinical grading of lymphedema of the lower limbs, and subjectively by means of the patient-reported perception of leg swelling. Health-related quality of life was evaluated using three different quality of life questionnaires. Two were generic: the SF-36 and EQ-5D-3L, and one was lymphedema-specific: the LYMQOL. Intraabdominal lymphocysts were evaluated by transvaginal ultrasound. Cost analysis of hospital costs was performed in relation to lymphadenectomy and lymphedema development.Results: The incidence of lymphedema varied between 9.5% and 29.6%, depending on the method of assessment of lymphedema. The highest incidence was found when using patient-reported swelling. The incidences of lymphedema were significantly higher in the lymphadenectomy group (14.9% - 38.1%) compared with the non-lymphadenectomy group (3.4% - 21.4%). The inter-rater agreement of lymphedema between the various methods of determining lymphedema was low. The incidence of lymphocysts was 4.3% and did not seem to pose a clinical problem. Lymphadenectomy per se did not seem to affect health-related quality of life negatively; however, lymphedema, independent of the method of assessing lymphedema, affected the lymphedema-specific quality of life significantly negatively, mainly in physical domains. Lymphadenectomy, age, and adjuvant radiation therapy were independent risk factors for lymphedema. Lymphadenectomy generated higher hospital costs, independent of the mode of surgery.Conclusions: A significant number of women develop lymphedema after lymphadenectomy in the treatment of endometrial cancer. The incidences vary, depending on the method of determining lymphedema. This inconsistency is also reflected in risk factors for lymphedema. Lymphadenectomy, increasing age, and adjuvant radiation are factors to pay attention to when planning treatment of endometrial cancer, not least because lymphedema has a negative impact on health-related quality of life. Lymphadenectomy is a cost-driving procedure and its use should be carefully evaluated in relation to its potential benefits.