Clinical Report: Efficacy Comparison of Neoadjuvant Radiotherapy Regimens

Overview

This systematic review and network meta-analysis evaluates the efficacy of short-course radiotherapy (SCRT) and long-course chemoradiotherapy (LCRT) regimens, with and without immunotherapy, for patients with proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC). The findings suggest that SCRT combined with immunotherapy may enhance pathologic complete response rates compared to LCRT regimens.

Background

Locally advanced rectal cancer (LARC) management has shifted towards multimodal approaches, primarily involving neoadjuvant radiotherapy followed by total mesorectal excision (TME). With over 90% of LARC cases being proficient mismatch repair (pMMR), understanding the optimal neoadjuvant strategy is crucial for improving patient outcomes. Recent advances in immunotherapy integration with radiotherapy present new opportunities for enhancing treatment efficacy.

Data Highlights

No numerical data available in the source material.

Key Findings

• SCRT-based regimens may achieve non-inferior or superior pathologic complete response (pCR) rates compared to LCRT-based regimens.
• The addition of immune checkpoint inhibitors (ICIs) to both SCRT and LCRT regimens significantly improves pCR rates in pMMR LARC cohorts.
• Modern treatment strategies emphasize total neoadjuvant therapy (TNT) to maximize tumor regression and facilitate organ preservation.
• Current guidelines recommend TNT as the default approach for stage II–III rectal cancer, particularly for high-risk patients.
• There is a notable absence of direct comparative trials between SCRT + ICIs and LCRT + ICIs, highlighting a gap in the evidence base.

Clinical Implications

Clinicians should consider the potential benefits of SCRT combined with immunotherapy for pMMR LARC patients, particularly in the context of total neoadjuvant therapy. The evolving landscape of treatment strategies necessitates careful patient selection and consideration of individual tumor biology to optimize outcomes.

Conclusion

This analysis underscores the need for further research to directly compare SCRT and LCRT regimens with immunotherapy in pMMR LARC, as current evidence suggests promising efficacy for SCRT-based approaches.

References

1. Techniques in Coloproctology, 2025 -- Efficacy and Safety of Short-Duration Radiotherapy Combined with Immunochemotherapy in Rectal Cancer with Proficient Mismatch Repair: A Perioperative Assessment
2. The ASCO Post, 2021 -- Total Neoadjuvant Therapy vs Standard Therapy for Locally Advanced Rectal Cancer
3. The ASCO Post, 2025 -- Total Neoadjuvant Therapy and Nonoperative Management in pMMR/MSS Stage II to III Rectal Cancer
4. The ASCO Post, 2025 -- Impact of Duration of Neoadjuvant Immunotherapy in MMRd Colorectal Cancer
5. Management of Locally Advanced Rectal Cancer: ASCO Guideline, 2024
6. Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial - PMC
7. NRG Oncology Study Determines Total Neoadjuvant Therapy with Pembrolizumab and Chemoradiotherapy is Safe, but May Not be Beneficial for Patients with Locally-Advanced Rectal Cancer - NRG Oncology
8. Management of Locally Advanced Rectal Cancer: ASCO Guideline
9. Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial - PMC
10. NRG Oncology Study Determines Total Neoadjuvant Therapy with Pembrolizumab and Chemoradiotherapy is Safe, but May Not be Beneficial for Patients with Locally-Advanced Rectal Cancer - NRG Oncology