Review ArticleStandardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers
Introduction
Lower extremity lymphedema (LEL) is an abnormal accumulation of fluid, which in gynecologic cancers occurs below the navel and can involve the bilateral legs and feet, the lower abdomen, bilateral hip area and genitals. LEL is a multifaceted disease of waxing and waning nature requiring quantitative objective measurements and qualitative subjective measurements, in addition to potential known risk factors (i.e., body mass index [BMI], age, race, and presence of pre-clinical lymphedema [LE]) and treatment factors (i.e., sentinel lymph node [SNL} dissection versus lymphadenectomy [LD], +/− radiation therapy, and +/− chemotherapy) for full assessment.
Lack of standardization regarding the definition and quantification of LE has been an ongoing barrier limiting the ability to move knowledge in this field forward [1]; however, advancing understanding is critical due to the potential for progression. Given the non-linear relationship between symptoms and severity of LE, even those with minimal early swelling may be symptomatic, leading to increased morbidity and a costly burden on both patients and the healthcare system.
There has been more research on post-operative LE related to breast cancer compared to gynecologic cancers. Therefore, the incidence of LEL has been under-recognized with comparatively limited data on the physical and emotional impact of LEL [2]. However, many gynecologic cancer survivors are living with discomfort, disfigurement, disruption of activities, and diminished quality of life because of LEL. For some, this is further compounded by recurrent infections and hospitalizations that lead to the degradation of a patient's condition and eventual disability.
The ability to differentiate swelling from multiple pre-operative cofounders (i.e., obesity, venous stasis or insufficiency) and normal post-surgical swelling from the signs or symptoms of developing LE is critical to the proper assessment of LEL. To avoid the overestimation of LE incidence and diminish the risk of post-operative swelling being attributed to LE, a designated time period after surgery (i.e., three months) should not be factored into the LE analysis. In the Gynecologic Oncology Group (GOG) 244, the Lymphedema and Gynecologic Cancer Study (The LEG Study), a multi-institutional study of 1054 women newly diagnosed with endometrial, cervical, and vulvar cancer who received surgery with a lymphadenectomy (LD) as primary intervention, LEL was greatest in the 4–6 weeks post-operative period, however, peak LEL appeared to be from 6 to 12 months and then taper through 2 years [3]. Although peak incidence of LEL may be six to twelve months, clinical trials should collect data for at least an 18–24 months post-surgery for complete assessment.
Section snippets
Measurement of lower extremity lymphedema
Four techniques have most often been employed to measure LE: (1) circumferential measurements (2) perometry, (3) water displacement, and (4) bioimpedance spectroscopy (BIS), with perometry and BIS largely restricted to the upper extremities in widespread usage thus far. Water displacement, due to impracticality and potential for imprecision, has largely been replaced by circumferential measurements via tape measures. However, these measurements can be imprecise and present challenges when
Objective measurement: bioimpedance spectroscopy (BIS) and emerging technologies
Over the past three decades, BIS has increasingly been used to screen for breast-cancer-related LE [5]. The National Lymphedema Network [6] position paper on screening and measurement for early detection of breast-cancer-related LE supports the use of BIS as an alternative to circumferential tape measurements. Yet, the Breast Cancer Evaluation Database to Guide Effectiveness Task Force rated BIS, circumference measurement, and water displacement each as Level 4 (highly recommended) due to good
SLNB —value in gynecologic cancer
At the core of advancing prevention is the need to evaluate the benefits and risks of SLNB in both cervical and endometrial cancer. Based on our current knowledge, we must investigate whether SLNB can become the standard of care by improving quality of life without impacting recurrence or survival.
Typically, patients with clinical stage I endometrial cancer have a good prognosis and are at low risk for lymph node metastasis. The primary role of lymphadenectomy (LD) in the treatment of
Patient-reported outcome assessment tools
In addition to quantitative measurements, physical examination, symptoms, and patient-reported outcomes (PRO) all contribute to the initial diagnosis and progression of LE.
For a PRO instrument to be effective, it must be brief, simple to complete, easy to score, and cover content consistent with clinical understanding of the signs and symptoms commonly reported in patients with LEL.
The Lymphedema Symptom Intensity and Distress Survey-Lower Limb (LSIDS-L) is a brief assessment tool that evolved
Summary and future goals
Research to date and the practical clinical experience of experts in attendance at the workshop, points strongly toward the need for standardization of optimal LEL quantitative measurements and baseline measurements prior to surgical intervention, as well as, the integration of PROs into gynecologic oncology protocols. Findings across sites and studies show potential for (a) improvements in protocol adherence and patient compliance to protocol measurements, (b) pre-operative baseline
Author contributions
Study concept and design: All authors.
Provision of materials or patients: All authors.
Acquisition of data: All authors.
Analysis and interpretation of data: All authors.
Manuscript writing: All authors.
Critical review of the manuscript: All authors.
Final approval of manuscript: All authors.
Financial support
The National Cancer Institute, Division of Cancer Prevention provided the financial support for the workshop meeting and preparation of the article.
Declaration of Competing Interest
Dr. Walker, Dr. Carlson, Dr. Carter, Dr. Covens, Dr. Tanner, Dr. Amer, Dr. Hayes, Dr. Lopez-Acevedo, Dr. Davidson, Dr. Schaverien, Dr. Ghamande, Dr. Cheville, Dr. Yost, Dr. Schmitz, Dr.Ford and Michael Bernas report no conflicts of interest. Dr. Russo and Dr. McCaskill-Steven report grants from government to support this workshop. Dr. Ward reports personal fees from Impedimed Inc., outside the submitted work. Dr. Ridner reports grants from Impedimed, during the conduct of the study. Dr. Taghian
References (44)
- et al.
GOG 244 - the lymphedema and gynecologic cancer (LEG) study: incidence and risk factors in newly diagnosed patients
Gynecol. Oncol.
(2020) - et al.
A pilot study of lower extremity lymphedema, lower extremity function, and quality of life in women after minimally invasive endometrial cancer staging surgery
Gynecol. Oncol.
(2019) - et al.
Diagnostic accuracy of bioimpedance spectroscopy in patients with lymphedema: a retrospective cohort analysis
J. Plast. Reconstr. Aesthet. Surg.
(2018) - et al.
Peripheral magnetic resonance lymphangiography: techniques and applications
Tech. Vasc. Interv. Radiol.
(2016) - et al.
Evaluation of lymphedema in upper extremities by MR lymphangiography: comparison with lymphoscintigraphy
Magn. Reson. Imaging
(2018) - et al.
Establishing a sentinel lymph node mapping algorithm for the treatment of early cervical cancer
Gynecol. Oncol.
(2011) - et al.
Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer
Gynecol. Oncol.
(2017) - et al.
The sentinel node procedure in early stage cervical cancer, taking the next step; a diagnostic review
Gynecol. Oncol.
(2015) - et al.
Sentinel lymph node biopsy for early cervical cancer: results of a randomized prospective, multicenter study (SENTICOL 2) comparing adding pelvic lymph node dissection vs. sentinel node biopsy only
Gynecol. Oncol.
(2017) - et al.
Sentinel lymph node biopsy vs. pelvic lymphadenectomy in early stage cervical cancer: is it time to change the gold standard?
Gynecol. Oncol.
(2010)