LYMPHA Technique to Prevent Arm Lymphedema After Breast Cancer Treatment: 15-Year Follow-Up

Authors: Boccardo F, Santori G, Fedre B, Fregatti P, De Paoli F, Murelli F, Dessalvi S, De Cian F

Affiliation: University of Genoa and San Martino Polyclinic Hospital, Genoa, Italy

Journal: Annals of Surgical Oncology, July 2026

PMID: 41886031

Key takeaways

• At up to 15 years, arm lymphedema occurred in 6/270 (2.2%) patients undergoing ALND with LYMPHA versus 95/230 (41.3%) without LYMPHA.

• The apparent benefit persisted despite radiotherapy: lymphedema developed in 2.5% with LYMPHA plus radiation versus 45% without LYMPHA plus radiation.

• Most lymphedema presented within 24 months, and no new cases occurred after 36 months in this cohort.

• The magnitude and durability of effect are striking, but the study is retrospective and nonrandomized, so causal certainty remains limited.

Background

Axillary lymph node dissection (ALND) remains necessary for selected breast cancer patients and carries a substantial lifelong risk of breast cancer-related lymphedema. LYMPHA, an immediate lymphatic reconstruction technique, attempts to restore arm lymphatic drainage at the time of ALND.

Objective

Assess the long-term effectiveness of LYMPHA for primary prevention of arm lymphedema after ALND, with follow-up extending to 15 years.

Methods

• Design: Retrospective, single-center observational cohort.

• Population: 550 consecutive Caucasian women undergoing ALND from January 2008 through July 2009; 500 completed long-term follow-up and were analyzed.

• Groups: 270 underwent ALND plus LYMPHA; 230 underwent ALND without preventive microsurgery. Radiotherapy exposure was identical at 75.2% in each group.

• Selection: LYMPHA use was determined preoperatively by microsurgical team availability, organizational factors, and patient preference. Three attempted LYMPHA cases without suitable lymphatics were excluded.

• Technique: Dual tracer mapping with blue dye and indocyanine green achieved 99% lymphatic identification. Two to four brachial lymphatics were anastomosed to a preserved collateral axillary venous branch using a sleeve technique under 15x to 20x microscopy.

• Outcomes: Lymphedema was defined as at least 5% excess arm volume versus the contralateral arm or tissue dielectric constant ratio at least 1.4. Assessments were every 6 months for 2 years, then annually.

• Statistics: Mann-Whitney U, chi-square, Kaplan-Meier analysis, and log-rank testing; two-tailed alpha 0.05. No power calculation or multivariable adjustment was reported.

Results

• Overall lymphedema: 6/270 (2.2%) with LYMPHA versus 95/230 (41.3%) without LYMPHA.

• With radiotherapy: 5/203 (2.5%) with LYMPHA versus 78/173 (45%) without LYMPHA.

• Without radiotherapy: 1/67 (1.5%) with LYMPHA versus 17/57 (30%) without LYMPHA.

• 15-year lymphedema-free cumulative probability: 0.978 with LYMPHA versus 0.587 without LYMPHA, p < 0.001.

• Lymphedema onset ranged from 6 to 36 months, with most cases in the first 24 months. All affected patients required long-term conservative therapy.

• Axillary web syndrome occurred in 5 (2%) LYMPHA patients versus 97 (42%) controls.

• Baseline age, BMI, arm volume, TDC ratio, radiation, number of nodes removed, nodal burden, chemotherapy, and breast surgery type were similar between groups.

Conclusion

The authors conclude that LYMPHA is an effective method for primary prevention of secondary arm lymphedema after ALND, with a preventive effect that appears durable through long-term follow-up.

Strengths

• Exceptionally long follow-up, with mean follow-up of 13.2 years and assessment out to 15 years.

• Large cohort with standardized serial arm volumetry and tissue dielectric constant measurements by trained lymphedema therapists.

• Balanced major treatment-related lymphedema risk factors between groups, including radiotherapy, nodal burden, chemotherapy, and breast surgery type.

• Detailed technical description from the group that originally developed LYMPHA.

Limitations

• Retrospective, nonrandomized design with potential selection and center-expertise bias; treatment depended partly on team availability and patient preference.

• Fifty of 550 patients were lost to or lacked complete long-term follow-up.

• No multivariable model, propensity adjustment, or randomized comparison was used to address residual confounding.

• The paper contains a reporting inconsistency on page 6, stating that the groups 'did not differ significantly' in 15-year volume/TDC changes while also reporting p < 0.01.

• Generalizability to lower-volume programs is uncertain because the procedure used dual tracers, dedicated lymphatic microsurgeons, operative microscopy, and an acknowledged learning curve.

Clinical relevance

For patients who truly require ALND, this study provides unusually long-term support for immediate lymphatic reconstruction. The effect size is clinically large and remains apparent in irradiated patients, making LYMPHA highly relevant when microsurgical expertise and coordinated axillary planning are available.

Editorial notes

This is one of the most important long-term datasets supporting immediate lymphatic reconstruction. The headline result is difficult to ignore: lymphedema occurred in 2.2% with LYMPHA versus 41.3% without it, an absolute difference of about 39 percentage points. That translates to an approximate number needed to treat of 3, although this is a simple calculation from an observational study and should not be interpreted as randomized efficacy.

The strongest message is durability. The Kaplan-Meier curves separate early and remain essentially flat after 3 years, suggesting that successful immediate reconstruction may alter the long-term trajectory of lymphatic failure rather than merely delay its presentation.

The major caveat is causal inference. This is not a randomized comparison, and the procedure was performed by a highly specialized team using dual mapping, microscope-based anastomosis, and 2 to 4 lymphatic channels. The enormous difference between groups may reflect a true biologic effect, but the study design cannot fully exclude selection, surveillance, or expertise effects. I would view these data as compelling support for offering immediate lymphatic reconstruction during ALND at experienced centers, while recognizing that reproducibility depends heavily on technique and team execution.