Radiotherapy may cut lymphoedema risk

Radiotherapy to the armpit instead of surgery may cut lymphoedema risk in some breast cancer patients, early trial results suggest.

Lymphoedema is swelling of the arm or armpit that can happen after surgery to remove lymph nodes.

New findings suggest axillary radiotherapy may be as effective at killing any remaining cancer cells while being less likely to trigger this complication.

The results come from the pilot phase of a phase III randomised international clinical trial looking at whether axillary radiotherapy has a lower risk of lymphoedema than axillary lymph node dissection in breast cancer patients who have had chemotherapy or hormone therapy before surgery, and whose cancer has spread to only one or two lymph nodes.

The trial will also assess overall survival and disease-free survival.

The researchers stressed that these are preliminary results from two years of follow-up in the pilot study, and that clinicians should wait for results from the ongoing phase III trial before considering changes to clinical practice.

Amparo Garcia-Tejedor, from the Functional Breast Unit at Bellvitge University Hospital in Spain and the Institut Català d’Oncologia, is leading the trial.

She said studies had already shown that axillary radiotherapy was a good alternative to axillary lymph node dissection in patients whose first line of treatment was surgery.

She said: “In situations where patients have received chemotherapy or hormone therapy before surgery, it is expected that results could be similar. However, robust prospective data are not yet fully established or published.

“Many patients treated with neoadjuvant therapy experience a significant reduction in axillary disease burden and ultimately present with only one or two lymph nodes that are positive for cancer metastases, which often correspond to the sentinel lymph node, while the remaining axillary nodes are negative.

“This observation strongly suggested that further axillary surgery might be unnecessary in a substantial proportion of patients and that a strategy of de-escalation should be explored.”

From June 2021 to April 2023, the ADARNAT trial recruited 272 breast cancer patients whose disease might have spread to one or more lymph nodes.

The patients had received neoadjuvant therapy and, at the time of surgery, had metastatic cancer in one or two sentinel lymph nodes, the lymph nodes where cancer typically spreads first.

Patients were randomised to receive either axillary radiotherapy or axillary lymph node dissection, and patients in both groups also received radiotherapy to areas of the breast and chest. Results were available for 46 patients in the radiotherapy group and 56 in the surgery group, with a median follow-up of two years.

No cancer recurred in the axillary area in the radiotherapy group, compared with one recurrence in the surgery group, or 1.8 per cent.

Cancer spread to other parts of the body in 4.4 per cent of radiotherapy patients and 5.5 per cent of surgery patients, and there were two deaths in the surgery group, or 4.3 per cent.

Lymphoedema was more common after surgery, at 26.7 per cent, than after radiotherapy, at 18.9 per cent, although the researchers said this difference was not statistically significant. Disease-free and overall survival rates were similar after two years.

Garcia-Tejedor said: “These results indicate that ART instead of ALND is feasible and has good cancer outcomes at two years.

“While some specialists have already begun to substitute axillary lymph node dissection with axillary radiotherapy without waiting for definitive results, the only way to determine with certainty whether this strategy is truly safe and effective is through participation in a well-designed clinical trial such as the one we are now conducting.

“This is particularly important given that the study population includes patients with residual axillary disease and, therefore, a potentially worse prognosis.

“In this context, treatment decisions should not be made without robust evidence.

“Our trial is designed to provide the necessary data to definitively answer this question and to ensure that any future change in standard practice is safe in terms of cancer outcomes and is also beneficial for patients.”

Maria Laplana-Torres, a radiation oncologist at the Hospital Clínic de Barcelona, presented pilot-phase results showing that although axillary radiotherapy was linked to more skin damage from radiation, this was usually temporary and easily treated.

Acute skin damage of grade 2 or above occurred in 27.8 per cent of radiotherapy patients compared with 13.3 per cent after surgery.

It mainly involved skin redness, pigment changes or, in some cases, skin peeling. There were no significant differences in later skin damage between the two groups.

She said: “Some patients experienced mild, temporary difficulty raising the arm above the shoulder or lifting it to the side. These limitations were usually short-lived and did not affect everyday activities.

“We found that treating the axilla with radiotherapy instead of extensive surgery can avoid a more aggressive operation without compromising treatment safety in patients with sentinel lymph node involvement.

“One and two years after treatment, there were no meaningful differences in arm mobility or quality of life between the two groups, although there was a more favourable trend in the ART patients.

“These results show that axillary radiotherapy may be a safe and less invasive option for some women treated with chemotherapy or hormone therapy before surgery.’

“This kind of research is essential to continue improving patient outcomes and to define safer, equally effective therapeutic approaches.”

More than 500 patients have now joined the main phase III trial. The researchers estimate that about three more years will be needed to complete recruitment, followed by five years of follow-up to fully assess cancer outcomes.