Efficacy and Safety of SCRT Plus Immunochemotherapy in pMMR Rectal Cancer

Overview

This study compares short-duration radiotherapy combined with immunochemotherapy (SCRT + ICT) to conventional neoadjuvant chemoradiotherapy (NCRT) in patients with mismatch repair-proficient (pMMR) rectal cancer. Results indicate that SCRT + ICT improves pathological complete response (pCR) rates and sphincter preservation without increasing perioperative complications.

Background

Immunotherapy has shown significant efficacy in mismatch repair-deficient colorectal cancer but is less effective in the majority of rectal cancer patients who are mismatch repair-proficient (pMMR). Radiotherapy can modulate the tumor immune microenvironment, potentially sensitizing pMMR tumors to immunotherapy. Combining radiotherapy with immunotherapy is emerging as a promising strategy to enhance neoadjuvant treatment outcomes in pMMR rectal cancer. This study directly compares SCRT + ICT with standard NCRT to clarify their relative perioperative efficacy and safety.

Data Highlights

Key Findings

• SCRT combined with immunochemotherapy significantly increases pathological complete response rates in pMMR rectal cancer compared to conventional NCRT.
• The sphincter preservation rate is higher in patients receiving SCRT + ICT, potentially allowing more patients to avoid permanent stomas.
• SCRT + ICT does not increase perioperative complications or surgical difficulty compared to NCRT.
• Immunotherapy regimens included PD-1, PD-L1, and CTLA-4 inhibitors administered over 3–6 months alongside chemotherapy and radiotherapy.
• A "watch and wait" approach was considered for patients achieving complete clinical response after SCRT + ICT, individualized by multidisciplinary evaluation.

Clinical Implications

Incorporating short-duration radiotherapy with immunochemotherapy offers a promising neoadjuvant treatment option for pMMR rectal cancer patients, improving tumor response and sphincter preservation without added surgical risk. This approach may expand the feasibility of sphincter-sparing surgery or nonoperative management strategies. Multidisciplinary evaluation remains essential to tailor treatment and follow-up plans.

Conclusion

SCRT combined with immunochemotherapy enhances perioperative outcomes in pMMR rectal cancer, representing a viable alternative to conventional long-course chemoradiotherapy. Further studies are warranted to optimize regimens and confirm long-term benefits.

References

1. NCCN Guidelines 2024 -- Rectal Cancer Treatment
2. Dutch NICHE Study 2023 -- Neoadjuvant Dual Immunotherapy in Colon Cancer
3. Japanese Voltage Study 2023 -- Nivolumab Consolidation in MSS Rectal Cancer
4. Recent RCTs 2024 -- Neoadjuvant Chemoradiotherapy Plus Immunotherapy in pMMR Rectal Cancer