Although the exact incidence of treatment-related lymphedema among cancer survivors is unknown—most likely due to its prolonged latency period—it can be a lifelong chronic side effect that negatively impacts survivors’ quality of life. Although the condition is often linked to treatment for breast cancer, lymphedema can occur after treatment for any cancer type that requires lymph node removal or radiation therapy in any lymph node basin, potentially affecting the lives of millions of cancer survivors.1
Characterized by the accumulation of lymphatic fluid in the soft tissues, most commonly of a patient’s arms or legs, lymphedema can cause lasting damage to limbs and lead to serious complications (including cellulitis, lymphangitis, thickening or hardening of the skin, and stiff joints). The condition can also heighten patients’ level of anxiety and depression and may result in a significant financial burden.
Sarah A. McLaughlin, MD, FACS
During the ASCO20 Virtual Education Program in August, Sarah A. McLaughlin, MD, FACS, Professor of Surgery and Chair, Division of General Surgery, Section of Surgical Oncology, at the Mayo Clinic in Jacksonville, Florida, presented a review of study data on the surgical and radiation oncology considerations to reduce the risk of lymphedema. The ASCO Post talked with Dr. McLaughlin about the perils of this common condition, how clinicians can reduce patients’ lymphedema risk, and the role palliative medicine plays in reducing the symptom burden for patients.
Determining the Long-Term Risk of Lymphedema
How soon after lymph node removal in the treatment of cancer do patients experience symptoms of lymphedema?
We know that between 80% and 90% of women treated for breast cancer who are likely to experience lymphedema will present with the condition between 6 months and 3 years following treatment. However, some studies have demonstrated there is an ongoing risk of about 1% per year for up to 20 years. So, the risk can be immediate or long term, which is why the condition is considered common but underreported, because most studies do not follow patients long enough to document its true incidence.
In general, studies suggest that for patients who have a sentinel lymph node biopsy in which just a couple of lymph nodes are removed, the risk of lymphedema is between 3% and 5%. If there is axillary dissection in which all of the lymph nodes are removed, the risk is between 15% and 20%. However, if there is axillary dissection followed by radiation therapy, the risk doubles to between 30% and 40%, so it is a pretty significant problem for these patients.
Anything we can do to decrease the number of lymph nodes removed during surgery or to reduce the amount of radiation therapy to the lymph node basin, the more likely we will be able to reduce the risk of the development of lymphedema.
Lymphedema can affect multiple parts of the body and may have a profound effect on the quality of life of patients. Is lymphedema potentially a lifelong problem for survivors?
It definitely is a lifelong concern for patients. A major area of research now is to determine how to identify the condition when there might be subtle changes in the lymphatic flow, but before there is evidence of swelling, so we can intervene earlier and prevent lymphedema from developing.
Jamie H. Von Roenn, MD, FASCO
As I mentioned previously, there can be a late onset of the condition after treatment, but that isn’t talked about much because patients are so glad to be cured of their cancer, they aren’t thinking about a potential life-altering problem such as lymphedema. However, lymphedema may have a significant impact on a patient’s life, because it is a constant reminder of the cancer diagnosis, and the condition requires a great amount of time-consuming care, including massage, lymphatic drainage, and compression sleeves. This is why lymphedema is a feared complication after breast cancer surgery or surgery for any cancer in which lymph nodes are removed; it is very difficult to predict which patients will develop the condition, and it is a nuisance to manage.
When we were performing much more extensive nodal dissection, there was a much higher prevalence of severe lymphedema, in which an arm or leg was more than 20% larger than the healthy limb. Trends today in the deliberate de-escalation of surgical intervention of lymph nodes suggest that more patients have a mild to moderate form of the condition. However, even in this early to moderate stage, unless there is intervention, the problem can progress to more severe disease.
Is there a way to determine which patients might be good candidates for de-escalated therapy?
Much of our ability to determine who might benefit from de-escalated surgical therapy comes from several clinical trials, which show that many patients do not do better or live longer because we remove more lymph nodes that are negative or free of cancer. We even recognize that, in select patients who have a small volume of cancer in the lymph nodes (ie, only one or two sentinel nodes that are positive for cancer), removing more lymph nodes that are probably negative does not prolong survival.
“In select patients who have a small volume of cancer in the lymph nodes, removing more lymph nodes that are probably negative does not prolong survival.”— Sarah A. McLaughlin, MD, FACS
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We also know there are other factors that increase the risk for lymphedema, including obesity, having a larger number of positive lymph nodes, and certain chemotherapies. We think about all of these factors when we weigh the risks and benefits of how best to manage the cancer. This is why it is so important to personalize treatment for patients and not have a one-size-fits-all approach.
Reducing the Risk of Lymphedema: Axillary Reverse Mapping
In your presentation, you talked about how there is a significant reduction in lymphedema risk in patients undergoing axillary reverse mapping. How might axillary reverse mapping reduce lymphedema risk?
The breast has lymphatic pathways that drain into the axilla. The upper extremity also has designated lymphatic pathways and lymph nodes that drain into the axilla. Axillary reverse mapping facilitates the identification and avoidance of upper extremity lymphatics within the axilla. In axillary reverse mapping, technetium is injected into the breast, and isosulfan blue dye is injected into the ipsilateral upper arm to identify the lymphatics that are draining from the arm. The theory is that, by protecting those blue lymph nodes and blue lymphatics, lymphatic flow from the arm is maintained, reducing the risk of upper extremity lymphedema.
With axillary reverse mapping, there is relatively good salvage of the arm lymph nodes and pathways, up to 80%, but the incidence of finding crossover drainage, in which the lymph node may drain both the arm and the breast does happen. There is also an incidence of cancer found in these arm lymph nodes, so more research is needed regarding the benefit of axillary reverse mapping.
Clinical trials are currently evaluating the feasibility and impact of axillary reverse mapping on lymphedema rates. Single-institution data suggest axillary reverse mapping results in a significant reduction in lymphedema.2
Identifying Early Lymphedema
Please talk about the importance of screening patients before cancer treatment using the prospective surveillance model for the early identification and treatment of lymphedema.
For many years, we practiced the reactionary model of care in which we waited for patients to develop lymphedema and then we tried to intervene. The prospective surveillance model of care provides a strategy to educate, support, and empower patients about the risks of lymphedema before they have any type of intervention, including surgery, chemotherapy, or radiation therapy, and then we monitor them for symptoms of the condition and provide early intervention.
Before treatment is initiated, a baseline assessment should be made to establish patients’ level of limb function and measurements taken of the ipsilateral and contralateral arms. Both objective and subjective assessments should be performed. Then, at each interval screening following treatment—every 3 months during active treatment to every 6 months for patients at low risk for lymphedema—we address the same objectives for lymphedema prevention and look for any subtle volume changes in limbs that may signal the start of early lymphedema.
If a 5% or higher increase is found in an affected limb from the baseline measure compared with the contralateral limb, that triggers patient intervention. Further, if we do find symptoms of the condition, clinical interventions to reduce limb volume—for example, the application of compression garments, fitted and prescribed for each patient; self-manual lymphatic drainage techniques; and exercise—are recommended.
If a patient has advanced cancer and we know axillary dissection and axillary radiation will be necessary, we act preemptively to get the patient referred to a lymphedema therapist for formal education regarding prevention strategies and options to reduce the risk of the condition after treatment.
Using Palliative Care to Reduce Lymphedema Symptoms
What is the role of palliative medicine in reducing the development of treatment-related lymphedema, and how can palliative care help mitigate the condition?
A lymphedema specialist or a physical medicine and rehabilitation specialist should be part of a patient’s overall palliative care team. These specialists serve several roles, including patient education, disease prevention, and early intervention. Often, these specialists can see patients for a one-time consultation to evaluate personal risk factors before therapy and then design an exercise intervention with a physical medicine and rehabilitation physician when early symptoms appear.
A lymphedema therapist is an invaluable member of the palliative medicine team to help patients cope with both the physical and psychosocial symptom management of the condition. Most cancer centers and hospital-based cancer programs have a lymphedema therapist on staff. Patients can also find a certified therapist near their home through the National Lymphedema Network (https://lymphnet.org/find-treatment) and the Lymphology Association of North America (www.clt-lana.org/search/therapists/.html).
“A lymphedema therapist is an invaluable member of the palliative medicine team to help patients cope with both the physical and psychosocial symptom management of the condition.”— Sarah A. McLaughlin, MD, FACS
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The critical piece to providing personalized care for our patients is to acknowledge that lymphedema is a serious condition that can affect patients’ lifelong quality of life; the responsibility is on all of us as clinicians to minimize that risk. We need to educate our patients about this potential treatment side effect, alert them to the symptoms, and be diligent about supporting them throughout cancer survivorship (including through risk stratification, monitoring for symptom burden, and early detection and intervention).
It is critical for all clinicians treating patients with cancer to understand the available resources for lymphedema prevention and treatment, so patients can live high-quality lives following a cancer diagnosis and treatment.
DISCLOSURE: Dr. McLaughlin reported no conflicts of interest.
1. McLaughlin SA, Stout NL, Schaverien MV: Avoiding the swell: Advances in lymphedema prevention, detection, and management. Am Soc Clin Oncol Educ Book 40:1-10, 2020.
2. Tummel E, Ochoa D, Korourian S, et al: Does axillary reverse mapping prevent lymphedema after lymphadenectomy? Ann Surg 265:987-992, 2017.