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Lymphedema: Separating Fact From Fiction

29 Feb 2016


he incidence of breast cancer–related lymphedema has been difficult to quantify due to delayed onset of symptoms and the lack of standardized diagnostic criteria. A recent meta-analysis reports the incidence of breast cancer–related lymphedema to range from 0 to 3% after lumpectomy alone to as high as 65% to 70% after modified radical mastectomy (removal of breast and axillary lymph nodes) with regional nodal radiation.[3] Overall, 80% to 90% of women who will develop lymphedema do so within 3 years of treatment,[4,5] but the risk persists years later as the remaining 10% to 20% will develop lymphedema at a rate of 1% per year.[5] Petrek et al followed 263 patients and found that nearly 50% developed lymphedema by 20 years.[5] These data suggest that lymphedema is probably more common than generally reported, and clearly the length of follow-up in a given study influences the reported incidence. A uniform definition of lymphedema does not exist. Although volume displacement methods are considered the gold standard for diagnosis, these methods are cumbersome and unable to identify subclinical lymphedema. Thus, displacement methods are rarely used in clinical settings. Circumferential arm measurements performed with a nonelastic tape measure are commonly used to determine upper extremity size differences. It is essential to obtain baseline preoperative measurements of the ipsilateral and contralateral extremities, as differences of up to 2 cm may naturally exist between the dominant and nondominant arms at baseline.[6] Published literature demonstrates significant heterogeneity, as studies lack agreement on the location and minimal number of measurements performed. Furthermore, they use multiple definitions of what constitutes lymphedema, including measurement changes greater than 2 cm, volume increase of more than 200 mL, or percentage increases in volume (> 10% or > 20%) compared with baseline when controlled for changes in the contralateral arm.[7,8] Aside from objective measurements, some studies define lymphedema by patient subjective symptoms or patient perceptions of swelling. Controversy remains as to whether a measurement change or a patient’s perception of swelling should be considered diagnostic. While a measurement change is objective, measurements may be affected by inter-rater and even intra-rater variability affecting reproducibility. Perhaps more importantly, a defined measurement change may be asymptomatic in an obese patient, while a thin woman may be bothered by more subtle measurement changes not meeting measured criteria for lymphedema. Alternatively, a patient’s perception of swelling may more accurately diagnose symptomatic lymphedema, but this perception may be influenced by sensory changes from the surgery and additional adjuvant therapies. Further, women with surgery in their dominant arm may perceive functional issues to a greater degree than if it were the nondominant arm that was affected.[9] In fact, one study found only 41% of women with perceived swelling had circumferential arm measurement changes greater than 2 cm, the objective threshold used in the study to define lymphedema.[9] Several contemporary studies have evaluated the differences between measured and perceived lymphedema and have validated patient perceptions against physical therapist–directed measurements.[4,10] These studies conclude that each evaluation method is valid but not interchangeable, and they do not endorse one method over another. The clinical introduction of a single-frequency bioelectrical impedance device manufactured by Impedimed (Mansfield, Australia) can minimize both inter-rater and intra-rater variability seen with other measurement techniques. The device produces easily interpretable values measuring the changes in extracellular fluid when compared with the unaffected contralateral upper extremity. A score increase of 10 or more or one that registers outside the normal range should prompt intervention with a compression garment or a referral for physical therapy. Some investigators report that measurement of bioimpedance has improved sensitivity in detecting subclinical lymphedema up to 4 months prior to standard measurement changes.[11] For these reasons, the current National Lymphedema Network (NLN) breast cancer–related lymphedema guidelines recommend that all breast cancer patients receive pre- and post-treatment measurements (of any type) on both arms and encourage the use of bioimpedance spectroscopy or infrared perometry as alternatives to tape measures, to limit measurement variations.

ABSTRACT: Lymphedema is a feared complication of cancer treatment and one that negatively impacts survivorship. The incidence of breast cancer–related lymphedema ranges from 6% to 70%, but lymphedema may be a common and under-reported morbidity. No standard guidelines for its diagnosis and assessment exist. Although the true etiology of lymphedema remains unknown, radiation, chemotherapy, type of breast surgery, and extent of axillary surgery are commonly cited risk factors. However, the relationship between the number of nodes removed and the risk of lymphedema is not clearly correlated. Clinical trials are focusing on ways to reduce the need for axillary dissection even in the setting of a positive sentinel node, to help minimize axillary morbidity. Risk-reduction practices, including avoidance of skin puncture and blood pressures in the ipsilateral upper extremity, and precautionary behaviors such as wearing compression garments during air travel continue to be advocated by the medical and survivor communities, despite a lack of rigorous evidence supporting their benefit. Emerging data support exercise in at-risk and affected women with lymphedema when started gradually and increased cautiously.
Lymphedema: Separating Fact From Fiction

Lymphedema in right arm of patient; from Boris M, et al. Oncology. 11:99-109,1997
The most recent survivorship data from the Surveillance, Epidemiology, and End Results (SEER) database demonstrate a significant increase in the number of US cancer survivors over the last 30 years, from roughly 3 million in 1973 to nearly 12 million in 2008.[1] As a result, issues of survivorship have stimulated new focus for clinical trials, not only to determine the most effective therapeutic regimen (surgery, drug, or radiation) but also to identify the one with the least influence on future quality of life. Lymphedema has long been a feared complication of surgical cancer treatment, and notably one that negatively impacts survivorship. Fear of lymphedema stems from patient concerns regarding the chronic, progressive nature of the condition and the clinician’s relative inability to predict or prevent its development. Furthermore, decades of physician and allied health teachings based on opinion and theory have perpetuated the myths shrouding lymphedema risk, prevention, and treatment.
A vast body of literature documents the occurrence of breast cancer–related lymphedema, with more than 1400 articles indexed in PubMed-MEDLINE databases alone. Importantly, lymphedema also exists after surgery for non–breast-cancer-related malignancies, but data documenting this occurrence are rare in comparison. Recently, Cormier et al found only 47 studies between 1972 and 2008 with more than 10 patients that prospectively evaluated lymphedema as a primary or secondary outcome after treatment for melanoma, bladder, sarcoma, penile, prostate, vulvar, cervical, endometrial, or head and neck cancers.[2] The authors’ analysis of these studies demonstrated the overall incidence of lymphedema to be 16.3% after melanoma, 10.1% after genitourinary cancers, and 19.6% after gynecologic malignancies, and notes that lymphedema rates are higher when the lower rather than upper extremity is affected. Given the abundance of breast cancer data, this review will focus on breast cancer–related lymphedema. However, the principles and controversies discussed are relevant regardless of the type of malignancy to which the lymphedema is attributed.

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