Regional Nodal Irradiation After Response to Neoadjuvant Chemotherapy
Regional nodal irradiation (RNI) can be safely omitted in patients with initially node-positive breast cancer who achieve a pathologic complete response (ypN0) after neoadjuvant chemotherapy, as it does not significantly improve invasive breast cancer recurrence-free interval or overall survival. 1
Current Guidelines vs. New Evidence
Traditional Approach
- The National Comprehensive Cancer Network (NCCN) has historically recommended that decisions regarding radiation therapy after neoadjuvant chemotherapy should be based on pre-chemotherapy tumor characteristics, regardless of response 2
- For patients with clinical stage III disease who achieve pathologic complete response to neoadjuvant chemotherapy, radiation therapy has been traditionally recommended 3
- Strong consideration for RNI has been recommended for patients with 1-3 positive lymph nodes, with definitive recommendations for those with 4 or more positive nodes 2
New Evidence
- The NSABP B-51/RTOG 1304 trial (2025) specifically addressed whether RNI improves outcomes in patients with initially node-positive breast cancer who achieve ypN0 status after neoadjuvant chemotherapy 1
- After a median follow-up of 59.5 months, the addition of RNI did not significantly improve:
Clinical Decision Algorithm
Step 1: Assess Nodal Response to Neoadjuvant Chemotherapy
- Determine if patient has achieved pathologic complete response (ypN0) in previously positive nodes 1
- Confirm complete axillary evaluation was performed (sentinel lymph node biopsy or axillary dissection) 4
Step 2: Treatment Decision Based on Nodal Response
For patients with ypN0 status:
For patients with residual nodal disease (ypN+):
Safety Considerations
- No deaths related to protocol-specified therapy were reported in the NSABP B-51 trial 1
- Grade 4 adverse events occurred in only 0.5% of patients in the irradiation group versus 0.1% in the no-irradiation group 1
- Omitting RNI in appropriate patients may reduce the risk of lymphedema (25.0% with axillary lymph node dissection vs. 9.4% without) 5
Important Caveats
- This recommendation applies specifically to patients with initial clinical stage T1-T3, N1, M0 disease who achieve ypN0 status 1
- Careful patient selection remains important, as patterns of recurrence can vary 6, 5
- The decision to omit RNI should be made in the context of other patient and tumor characteristics 7
- Breast/chest wall radiation should still be considered according to standard indications 3
Conclusion
The NSABP B-51/RTOG 1304 trial provides high-quality evidence that RNI can be safely omitted in patients with initially node-positive breast cancer who achieve a pathologic complete response after neoadjuvant chemotherapy, representing a significant change from previous guideline recommendations that were based on pre-chemotherapy staging.