Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i1): The OPBC-05/ICARO Study

This study has explored the need for completion ALND in patients with residual isolated tumour cells after SLNB post neoadjuvant chemotherapy.  The standard management of these patients is completion clearance based on the premise that any residual disease after NACT will be innately resistant to the systemic therapy the patient received.   However, the validity of this approach was questioned because these patients often go on to receive second line systemic therapy (TDM1, PARPi, endocrine therapy, capecitabine) often combined with radiotherapy, which should be able to destroy these tiny clusters of cells.   The morbidity of ALND is considerable and this may be unnecessary over treatment.  

ICARO was a retrospective, International, multicentre cohort study, run by the Oncoplastic Breast Consortium of collaborators.   It reviewed data on 583 patients with ITCs in their SLNB after NACT who either had completion ALND (182/583, 31%) or no further surgery (401/583, 69%).   It reported on the rate of finding further disease in the ALND group, stratified by disease characteristics, and also the rate of axillary recurrence at median follow up of 3 years.

The patients were fairly young with a median age of 48, and with mixed stage, tumour biology and breast surgery.  Stage varied from I to III, (T1-T4, excluding inflammatory, cN0-N3).   Biology was 38% Her2+, 21% TNBC, 41% ER+/Her2-.  Roughly half of the patients had mastectomy.   A high proportion received either whole breast radiotherapy or chest wall radiotherapy or nodal radiotherapy.   The initial node sampling procedure was either dual tracer SLNB, TAD, or MARI.    

They found that the majority of patients who had ALND had no further nodal involvement and of those that did, these were further ITCs in the majority, with few patients having residual macrometastases.   The findings varied by the initial stage at diagnosis, with those who were clinically N0, 73% had no further disease, 17% ITC only, 7% micromets and 3% macromets.   In contrast in those with N2/3 disease at presentation 60% had no further disease, 30% had ITCs, 3% micrometastases and 7% macrometastases.   

The study found no significant difference in rates of axillary recurrence at 3 and 5 years and also that ALND had no impact of adjuvant therapy decision making.   They conclude that surgery for post-NACT patients with ITCs in their SLNs is not necessary in all patients.   
The study was observational and therefore subject to bias, in that women who did have an ALND were likely those with more aggressive disease, which might tend to increase the recurrence risk in these women.  However the data represent a very large series from multiple international sites, which gives validity to their findings and conclusions.

In some women, with low axillary disease burden (cN0, cN1), selective omission of ALND may be safe.

Longer follow up would be ideal.  

References:

1. Montagna G, Laws A, Ferrucci M, et al. Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study. J Clin Oncol 2025; 43(7): 810-20.

Summary author:

Professor Lynda Wyld: Professor of Surgical Oncology, University of Sheffield, Consultant Oncoplastic Breast Surgeon, Doncaster and Bassetlaw Teaching Hospitals.