Addition of prophylactic compression garments to standard care to prevent irreversible lower limb lymphoedema after gynaeco-oncological therapy (Gynolymph): protocol for a randomised controlled trial embedded within an observation cohort study.

INTRODUCTION

In female patients diagnosed with gynaecological cancer, the main priority is treating cancer itself. However, a significant number of these patients develop lower limb lymphoedema (LLL), with its incidence strongly influenced by the diagnostic cut-off (a difference in leg circumference between both legs of 5% or 10%). LLL significantly impacts patients' quality of life (QoL) due to functional impairment, the daily time investment required for treatment, financial costs and affected body image. Additionally, it increases the risk of cellulitis, often leading to hospitalisation for intravenous antibiotics. Timely recognition and acknowledgement of symptoms are crucial first steps in improving the QoL for these women. LLL is a common and irreversible complication following treatment for gynaecological cancer. Despite its clinical significance, there are limited prospective studies investigating LLL incidence, risk factors, early detection and clinical course in this patient population. Therefore, the objective of this observational cohort study is to investigate the incidence rate of stage 0-1 or stage 2-3 LLL based on the International Society of Lymphology criteria in the first 2 years after gynaecological cancer treatment. The embedded randomised control study (RCT) examines the added value of prophylactic compression garments (class II) to standard care in preventing irreversible lymphoedema after gynaeco-oncological therapy.

METHODS AND ANALYSIS

In June 2022, two university hospitals in Belgium initiated a multicentre observational cohort study, which also includes an embedded RCT. The study aims to enrol 400 patients before they begin cancer treatment or within 14 days of starting chemotherapy, radiotherapy or surgery. This cohort will be followed for up to 2 years. The embedded RCT will focus on patients who develop clinical lymphoedema stage 0-1 within the first 12 months following their initial cancer treatment. A total of 196 patients will be randomised into two groups: the intervention group (98 patients), receiving usual care plus prophylactic compression garments (compression class 2 (CCL2): 23-32 mm Hg), and the control group (98 patients), receiving only usual care. The RCT aims to assess the impact of adding prophylactic compression garments to standard care on further deterioration. Assessments will be conducted at baseline, and at 3, 12 and 24 months after initial cancer treatment. An additional assessment (T-visit) will be provided if there is a transition to LLL stage 0-1 or from stage 0-1 to stage 2-3 LLL, based on follow-up findings or patient initiative, using the predictive value of a validated self-report lower extremity questionnaire. This questionnaire is part of a lymph diary app provided to all patients. The primary outcome of the observational study is to determine the incidence rate of stage 0-1 or stage 2-3 LLL in the first 2 years after gynaecological cancer treatment. The primary outcome of the RCT is to evaluate the effect of wearing CCL2 preventive garments to avoid progression to higher-stage lymphoedema in patients who develop LLL within 1 year of treatment. Key secondary outcomes of the observational study include the timing of the development of LLL, risk factors for developing LLL and the impact of LLL on QoL and sexuality, as well as the evaluation of screening and diagnostic tools. The secondary outcomes of the RCT include tolerance and compliance with wearing the preventive compressive garments, the impact of the garments on limb volume and the patient's time and financial investment.

ETHICS AND DISSEMINATION

The study was approved by the Ethics Committee of the two academic hospitals: the University Hospital of Ghent in September 2021 and the University Hospital of Leuven in December 2021. Approval has been granted for the study protocol, informed consent forms and other related documents by the main Ethics Committee of Ghent (BC-09915) and the local Ethics Committee of Leuven (S65724). All patients will provide written informed consent before participating in the trial. The results will be shared through peer-reviewed journals and presentations.

TRIAL REGISTRATION NUMBER

NCT05469945.