New Data Recommend Continuous Monitoring of Lymphedema for Breast Cancer

Findings from the PREVENT study found that bioimpedance spectroscopy use may reduce progression to chronic lymphedema compared with tape measure use.

Patients who have completed breast cancer treatment are at an increased risk of developing lymphedema and may need to be monitored for at least 3 years following therapy completion, including careful targeted monitoring over the first 9-month period, according to the findings from the PREVENT study (NCT02167659) published in Annals of Surgical Oncology.¹

Findings from the randomized controlled study found that bioimpedance spectroscopy (BIS) use correlated with early detection and intervention of lymphedema, limiting progression to chronic lymphedema when compared with tape measure (TM) use. Additionally, early detection and intervention of subclinical breast cancer–related lymphedema (sBCRL) was integral in decreasing progression rates in chronic breast cancer–related lymphedema (cBCRL).

Within 9 months of breast cancer treatment, 52.6% of the patients had measurements consistent with sBCRL. For 2.5 years post-surgery, patients had detection of sBCRL regardless of screening method (P >.242). During the 3-year period, 39 patients progressed to cBCRL and did not develop sBCRL.

Over the 3-year monitoring period, 209 patients were triggered for sBCRL in each 3-month interval between the 2 groups. For the first 9 months after breast cancer treatment, the TM group had a higher trigger rate of 16.7% vs 7.2% in the BIS group (P <.0001). For the rest of the monitoring period, the trigger remained similar for both groups at 9.3% vs 12.3% (P = .1744), respectively.

In the TM group, at 9 months, the rate of progression after intervention was 24.7% (n = 19/77) vs 6.1% (n = 2/33) in the BIS group (P = .0446). Certain patients who had 4 weeks of intervention continued to cBCRL with a median time to progression of 18.8 months. Additionally, those who progressed between visits and prior to intervention during the 3-year monitoring period had a median time to progression of 10.2 months.

"Late-developing [cBCRL] is a particularly harsh blow to patients who thought they had put their treatment behind them," lead study author Chirag Shah, MD, co-director of the Comprehensive Breast Cancer Program at Cleveland Clinic and scientific advisor to ImpediMed, said in a news release on the study findings.² "Early detection and intervention are the keys to preventing chronic lymphedema. By showing that patients can develop breast cancer-related lymphedema from a few months to even years after treatment, this analysis highlights the need for careful screening for years following treatment."

The trial was designed to determine if a subclinical increase of extracellular fluid in the arm monitored by BIS plus early treatment may improve rates of cBCRL. The screening occurred using the L-Dex U400 to measure the impedance of both arms and report a score for the assessment of lymphedema.

Patients were followed up with at 3-, 6-, 12-, 18-, 24-, 30-, and 36-months post-surgery and could have optional 15- and 18-month visits. If sBCRL was identified during any visit, early intervention treatment was initiated.

Early intervention consisted of wearing a 22 mmHg to 32 mmHg compression sleeve and gauntlet for 12 hours a day for 4 weeks. Patients were measured at the end of the 4-week period to determine if a benefit occurred.

A total of 918 patients were randomly assigned to either the BIS group with subsequent early treatment for improved rates of cBCRL (n = 461) or the tape measurements (TM) with BIS group for detecting BCRL (n = 457). Risk factors for BCRL included body mass index, stage of cancer, axillary surgery, and radiation therapy. Additionally, there were significant differences between patients who were triggered for sBCRL and did not progress to cBCRL including stage of cancer (P <.001), axillary surgery (P = .003), and chemotherapy treatment (P = .015).

Of those enrolled, 22.8% developed sBCRL and were eligible for the 4-week compression sleeve intervention. Each group was monitored, with 19.3% by BIS and 26.3% by TM. Of the 30 patients who progressed to cBCRL, 7.9% were in the BIS group, and 19.2% were in the TM group.

The median time to trigger progression was 5.8 months vs trigger with no progression of 8.9 months (P = .007). Of note, there was no difference between trigger outcomes for the time between the previous visit and trigger visit. This included trigger progression of 4.2 months vs no trigger progression of 3.8 months (P = .4599). The investigators suggested monitoring treatment more frequently than every 3 to 4 months may not improve outcomes.

There was a delayed time to progression between years 1 and 2 for all those who progressed to cBCRL and those who triggered sBCRL and received early intervention (year 1: trigger, progression, 8.0 ± 2.5 months vs. progress, no intervention, 4.9 ± 2.4 months, p = 0.0039, year 2: trigger, progression, 18.9 ± 3.1 months vs. progress, no intervention, 15.9 ± 2.9 months p = 0.0428).

If patients did not receive early intervention before cBCRL, the median time to progression visit and the previous screening visit was consistent with the measurement frequency of the 6 monthly visits. In year 2, the median was 6.3 months (P = .5420), and at year 3, it was 6.2 months (P = .4962).Of these patients, 94.9% complied with protocol and showed that a 6-month screening may not be adequate post-surgery for patients who are high-risk.

The study follows guidelines from the Multinational Association of Supportive Care in Cancer (MASCC), which recommend BIS as an early lymphedema detection option.³

References

1. Shah C, Boyages J, Koelmeyer L, Chen SL, Vicini F. Timing of breast cancer related lymphedema development over 3 years: observations from a large, prospective randomized screening trial comparing bioimpedance spectroscopy (BIS) versus tape measure. Ann Surg Oncol. Published July 04, 2024. doi:10.1245/s10434-024-15706-x
2. Additional data published in "Annals of Surgical Oncology" recommends extended monitoring of lymphedema for breast cancer patients. ImpediMed. July 16, 2024. Accessed July 22, 2024. https://tinyurl.com/37zvhawz
3. Multinational Association of Supportive Care in Cancer. Update to lymphedema prevention and management: comprehensive evidence-based approaches. Revised February 27, 2024. Accessed July 22, 2024. https://tinyurl.com/39ac5cvr