Preventing Clinical Lymphedema With Bioimpedance Spectroscopy

Patrick W. Whitworth, MD

Breast cancer-related lymphedema affects from 3 million to 5 million people in the United States. Approximately 23,000 new cases (7% after sentinel node biopsy, 25% after axillary dissection) are expected this year. On top of the daily harm to quality of life, lymphedema can make it impossible for a patient to successfully move on from cancer treatment. And from an economic standpoint, a recent analysis of commercial payers found that within 2 years of treatment, a diagnosis of lymphedema adds $14,600 to the average cost of treatment for a patient with breast cancer.¹

But now, several breast cancer treatment programs are reporting a substantially reduced incidence of clinical lymphedema, particularly for patients at high risk after axillary dissection, radiation, or taxane-based chemotherapy. Employing preclinical detection using bioimpedance spectroscopy (BIS), breast centers are reporting progression to clinical lymphedema in less than 10% of such high-risk patients. How is such a significant reduction possible? The answer comes from one of the main principles in breast cancer treatment: early detection and tailored intervention.

To understand how such an improvement is possible with early detection, it’s helpful to recognize that lymphedema begins with a clinically undetectable increase in the ratio of limb extracellularto-intracellular fluid (stage 0 lymphedema). Sophisticated tape-measure and water-displacement techniques cannot detect stage 0 lymphedema. Stage 0 can be detected only by optical perometry, bioimpedance scanning, or lymphoscintigraphy. Stage I lymphedema is intermittent because tissues still retain their elasticity and fluid accumulation is reversible with elevation, compression, or even dehydration. Stage I lymphedema is detectable by all methods but only if it happens to be present during examination and measurement. Tissue elasticity is progressively and permanently lost in stage II, when all methods reliably detect lymphedema, but it is too late to prevent permanent fibrosis and loss of elasticity. Stage II is a chronic condition requiring a lifetime of caution and management, but without early detection, stage II is when most patients with lymphedema receive a diagnosis. In stage III, excess limb volume is actually due to accumulation of fat; very little fluid remains in the extracellular space in these most advanced cases.

Because BIS is widely available and noninvasive, it is the most commonly employed method for preclinical (stage 0) detection of lymphedema. In a prospective observational study from the University of Pittsburgh, 16 (36%) of 44 axillary dissection patients developed clinical lymphedema when monitored with regular tape measurements over 21 months. In comparison, only 2 (1.4%) of 136 patients progressed to clinical lymphedema when monitored with BIS after axillary dissection. Forty-five (33%) of 136 patients in the BISmonitoring group had a 10-point elevation in their lymphedema index (L-Dex) score (generated by the BIS technology used in the study). If a patient had a 10-point (3 standard deviations) elevation, she was managed with an OTC compression sleeve and massage, usually for 1 month. Presumably these are patients who would have progressed to clinical lymphedema in the same way that 36% of the control group did. At Nashville Breast Center, 3% of 596 patients (80% with high-risk features) monitored with BIS required ongoing decongestive treatment. In general, patients are monitored with BIS every 3 months for 2 years, then every 6 months for 3 more years. A 10-point elevation in the L-Dex score has been used as a trigger for intervention with an OTC compression sleeve and massage, usually for 4 weeks. In a multi-institutional prospective randomized trial led by Vanderbilt University, investigators are evaluating a 7-point (2 standard deviations) elevation as an effective cutoff to trigger intervention.

Compelling evidence that preemptive treatment can prevent progression to lymphedema comes from a prospective randomized trial reported in BMJ in 2010. Patients (n = 110) were randomized to receive regular, preemptive, decongestive physiotherapy, versus conventional patient education, and were followed for 1 year after axillary dissection.² In the education group, 25% of patients developed lymphedema. In the prevention group, lymphedema occurred in 7% of patients (P = .01). Although the trial provides level 1 evidence that lymphedema can be prevented with preemptive treatment, most clinicians believe preventive decongestive physiotherapy treatment for all patients at risk for lymphedema is impractical, cost-prohibitive, and unacceptable to patients. On the other hand, targeted intervention for patients found to have significant increases in limb extracellular-to-intracellular fluid ratio—when simple OTC sleeve compression is effective— appears practical, cost-effective, and acceptable to patients.

Estimating cost and savings with such an approach suggests potentially substantial costeffective results. Assuming the cost per BIS test is $125 (based on 2017 Medicare payment), 2 years of tests (every 3 months) for 100 patients would cost $100,000. Using the results from the randomized prevention trial, 7 of 100 axillary dissection patients monitored with BIS plus targeted simple intervention would develop clinical lymphedema at an added healthcare cost of $102,200 ($14,600 added cost from lymphedema over 2 years × 7 patients). For patients not monitored this way, the added cost would be $365,000 for the 25 patients expected to develop clinical lymphedema, yielding potential gross savings of $262,800 and net savings of $160,800 (subtracting $100,000 for BIS tests and estimating a $2000 cost for sleeves). Applying an estimated savings of approximately $160,000 per 100 patients to the group of approximately 40,000 US patients expected to develop lymphedema over 2 years yields an estimated potential savings of $64 million over 2 years. Considering that most experts accept a cost of $50,000 to $100,000 per quality adjusted life year (QALY), preclinical (stage 0) detection of lymphedema with effective simple intervention represents a rare opportunity to reduce healthcare costs and add QALYs at the same time.

References

1. Caudle AS, Hunt KK, Tucker SL, et al. American College of Surgeons Oncology Group (ACOSOG) Z0011: impact on surgeon practice patterns. Ann Surg Oncol. 2012;19(10):3144-3151. doi: 10.1245/s10434- 012-2531-z
2. Cheville A. Prevention of lymphedema after axillary surgery for breast cancer. BMJ. 2010;340:b5235. doi: 10.1136/bmj.b5235.