Breast
Surgical de-escalation of the axilla continues to lean on nodal RT rather than replace it.
SENOMAC NCT02240472
ForcN0 T1-T3 breast, 1-2 sentinel-node macromets, planned nodal RT
HR 0.89
95% CI 0.66-1.19, P<0.001 for noninferiority (margin 1.44)
TL;DR5yr RFS 89.7% vs 88.7% omitting completion ALND, HR 0.89 (0.66-1.19), noninferior in 1-2 SLN macromets.
The axilla here was irradiated, not left alone: 89.9% vs 88.4% received nodal target volumes, so this validates SLNB plus regional nodal RT, not surgical de-escalation without RT. Untreated non-SLN disease was present in 34.5%, meaning the RT field is carrying real burden. Nodal level doses and volumes are not yet reported.
In cN0 T1-T3 disease with one or two sentinel macrometastases, including mastectomy, T3 and extracapsular extension, this supports omitting completion dissection when regional nodal irradiation is planned; it does not speak to pts in whom nodal RT is being omitted.
Nodal target volumes were treated in 89.9% vs 88.4%, so the axilla was managed, not observed, and the RT field is covering the 34.5% non-sentinel-node burden the surgery would have removed. Doses and nodal levels are not yet reported, so the trial supports covering the regional nodes without specifying how.
Systemic therapy shares the load: approximately 65% received chemotherapy and 93% endocrine therapy, and 9.9% of dissected pts were upstaged to pN2 with 3.0% pN3, meaning omission removes nodal counts that currently inform adjuvant intensity. Decisions will rest on tumour biology and genomic tools rather than final node count.
Completion dissection can be omitted in the subgroups the earlier trials could not answer: mastectomy (36.7%), T3 (5.5%) and extracapsular extension, with 5yr RFS 89.7% vs 88.7%. The trade is accepting known residual disease, since 34.5% of dissected pts had additional non-sentinel-node metastases and 9.9% were pN2.
13 details 5 trials watching
Prospective randomized phase 3 noninferiority trial, 1:1, 67 hospitals in Sweden, Denmark, Germany, Greece and Italy. 2766 enrolled Jan 2015 to Dec 2021; per-protocol population 2540 (1335 sentinel-node biopsy only, 1205 completion dissection). Median follow-up 46.8 months (range 1.5 to 94.5).
cN0, T1 to T3 breast cancer with one or two sentinel-node macrometastases (>2mm). Preoperative axillary ultrasound was mandatory; suspicious nonpalpable nodes were still eligible even with FNA-confirmed metastasis. Additional micrometastases and extracapsular extension were allowed, and both breast-conserving surgery (63.3% / 64.3%) and mastectomy (36.7% / 35.7%) were eligible. Mean age 61.
RT including nodal target volumes was given to 89.9% (1192/1326) of the sentinel-node-only group and 88.4% (1058/1197) of the dissection group. Whole-breast RT was mandatory after breast-conserving surgery, but the protocol stipulated no specific target volumes or doses, deferring to national guidelines. QA on 1154 plans showed eCRF-to-plan concordance of 99.3% for breast or chest wall and 96.6% for nodal volumes.
Primary: overall survival (switched from breast cancer-specific survival in 2020 on DSMB advice). Prespecified secondary endpoints were recurrence-free survival, breast cancer-specific survival and patient-reported outcomes. Noninferiority required the upper CI bound for recurrence or death below 1.44.
No clinical lymphedema measurements were performed; arm morbidity relies on the LYMPH-ICF, QLQ-C30, QLQ-BR23 and EQ-5D questionnaires at 1, 3, 5 and 10 years. Only 1-year data from a Swedish-Danish subpopulation are published; 3-year data for the whole trial are not yet available.
Consistent with ACOSOG Z0011 and AMAROS, but the authors place SENOMAC alongside AMAROS and OTOASOR rather than Z0011, SINODAR-ONE or POSNOC, because nodal irradiation was routine here. Where the earlier trials enrolled nearly 40% micrometastasis-only pts, one T3 patient between them, and only 248 mastectomies (17.4%) in AMAROS, SENOMAC filled each of those gaps.
Detailed nodal level doses and volumes are not yet reported, so the RT dose actually treating the residual axilla is unquantified. Withdrawal was higher in the dissection arm, reflecting pts' wish to avoid the operation. The ER+/HER2+ subgroup HR of 0.26 (0.07-0.96) rests on 3 versus 10 events among 13 subgroups and should not be read as a real interaction.
The completion dissection arm shows what is being left behind: 34.5% (403/1167) had additional non-sentinel-node metastases, rising to 51.3% with two macrometastases, and 9.9% were upstaged to pN2 with 3.0% pN3. Noninferior recurrence-free survival despite that residual burden is a statement about what systemic therapy plus nodal RT can control, not about the axilla being clean.
| Event | SLNB only (N=1335) | cALND (N=1205) |
|---|---|---|
| Local recurrence | 12 (0.9) | 10 (0.8) |
| Regional recurrence | 6 (0.4) | 6 (0.5) |
| Distant recurrence | 44 (3.3) | 53 (4.4) |
| Death | 62 (4.6) | 69 (5.7) |
| Recurrence or death as first event | 95 (7.1) | 96 (8.0) |
CONSORT flow
Prespecified noninferiority met with wide margin to boundary; enrolls the mastectomy, T3 and ECE subgroups Z0011 and AMAROS excluded, resolving the residual uncertainty.
- Nodal RT target volumes and doses needed for this result n=1900 · primary completion 2026-07 · axillary treatment vs none, 1-2 SLN macrometsrecruiting The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases. Phase NAn=1350 · primary completion 2028-12 · omits regional RT in ER+ 1-2 SLN macrometsrecruiting Level I-II Axillary Irradiation in Breast Cancer With Sentinel-Node Macro-metastases Phase NAn=1608 · primary completion 2032-12 · level I-II axilla vs whole regional RT, SLN macromets
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