REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
This article is part of the Research TopicNational Colorectal Cancer Awareness Month 2025: Current Progress and Future Prospects on Colorectal Cancer Prevention, Diagnosis and TreatmentView all 19 articles
Neoadjuvant Therapy for pMMR / MSS Locally Advanced Rectal Cancer in the Immunotherapy Era: Current Landscape and Future Perspectives
Provisionally accepted
- 1School of Life Sciences, Lanzhou University, Lanzhou, China
- 2Gansu University of Chinese Medicine First School of Clinical Medical, Lanzhou, China
- 3State Key Laboratory of Herbage Improvement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University, Lanzhou, China
- 4Division of Radiation Oncology, Gansu Provincial Hospital, Lanzhou, China
- 5The Third Hospital and Clinical Medicine School, Lanzhou University, Lanzhou, China
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Numerous clinical studies indicate that neoadjuvant chemoradiotherapy (NCRT) with immunotherapy can significantly increase pathological complete response (pCR) and clinical complete response (cCR) rates to over 30-60%, substantially higher than the 15-20% observed with conventional NCRT. This allows more patients to become eligible for a Watch-and-Wait (WW) strategy, successfully preserving organ function. Several phase III randomized controlled trials (RCTs) are currently underway. The combination of NCRT and immunotherapy holds promise for breaking the therapeutic impasse in proficient mismatch repair/microsatellite stability (pMMR / MSS) rectal cancer, markedly enhancing tumor regression and the potential for organ preservation. However, challenges remain for NCRT combined with immunotherapy in this population. First of all, there is an unmet need to identify predictive biomarkers for treatment response in pMMR / MSS rectal cancer. Next, treatment protocols require further optimization, specifically in determining the best radiotherapy fractionation schedule, its sequencing with immunotherapy, and the radiotherapy target volume. Otherwise, the phenomenon of "pseudo-residual disease" complicates traditional radiological assessment of cCR and must be overcome. Furthermore, the long-term survival benefits of combining radiotherapy with immunotherapy need further confirmation. This review provided a comprehensive and in-depth view of immunotherapy-based NCRT (iNCRT) in patients with pMMR / MSS rectal cancer and discuss the new opportunities and challenges this strategy presents for achieving organ preservation.
Keywords: rectal cancer, pMMR/MSS, Immunotherapy, Watch and wait approach, pathological complete regression, Clinical complete remission, Long-course chemoradiotherapy, Short-course chemoradiotherapy
Received: 06 Oct 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 Farooq, Li, Xiao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaojun Liu, lxjmail2008@126.com
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