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Purpose <p>Microsatellite-stable (MSS) or mismatch repair-proficient (pMMR) metastatic colorectal cancer (mCRC) responds poorly to immune checkpoint inhibitors (ICIs). We investigated whether combining ICIs with radiotherapy (RT) promotes distant tumor regression and improves survival.</p> Methods <p>We retrospectively analyzed patients with MSS/pMMR mCRC treated with ICIs between October 2021 and November 2024. According to RT use, patients were divided into RT and non-RT (NRT) groups. Propensity score matching (PSM) was used to minimize selection bias. The primary endpoint was the out-of-field (abscopal) response rate (ARR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs), graded using Common Terminology Criteria for Adverse Events version 5.0.</p> Results <p>After PSM, 40 matched pairs were generated from the RT (<i>n</i> = 46) and NRT (<i>n</i> = 83) groups. ARR was higher in the RT group than in the NRT group (22.5% vs. 5.0%, <i>p</i> = 0.023). Median OS and PFS did not differ significantly between groups. Cox regression showed that pulmonary metastasis (<i>p</i> = 0.019) was an independent prognostic factor for OS. RT (hazard ratio = 0.466, <i>p</i> = 0.005) and neutrophil-to-lymphocyte ratio (<i>p</i> = 0.001) were independently associated with PFS. Lymphocytopenia was more frequent in the RT group (<i>p</i> = 0.006), with no other significant differences in TRAEs.</p> Conclusion <p>RT combined with ICIs significantly improved ARR in MSS/pMMR mCRC, suggesting clinical benefit with a manageable toxicity profile and supporting further investigation of this combination.</p>

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Efficacy of Radiotherapy Combined with Immunotherapy in MSS/pMMR Metastatic Colorectal Cancer: a Propensity-Matched Retrospective Study

  • 期刊论文

  • 发表日期：

    2025年12月22日

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  • Fengwei Mou,
  • Zheng Fang,
  • Jinwen Shen,
  • Ke Lu,
  • Lishu Lou

摘要

Purpose

Microsatellite-stable (MSS) or mismatch repair-proficient (pMMR) metastatic colorectal cancer (mCRC) responds poorly to immune checkpoint inhibitors (ICIs). We investigated whether combining ICIs with radiotherapy (RT) promotes distant tumor regression and improves survival.

Methods

We retrospectively analyzed patients with MSS/pMMR mCRC treated with ICIs between October 2021 and November 2024. According to RT use, patients were divided into RT and non-RT (NRT) groups. Propensity score matching (PSM) was used to minimize selection bias. The primary endpoint was the out-of-field (abscopal) response rate (ARR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs), graded using Common Terminology Criteria for Adverse Events version 5.0.

Results

After PSM, 40 matched pairs were generated from the RT (n = 46) and NRT (n = 83) groups. ARR was higher in the RT group than in the NRT group (22.5% vs. 5.0%, p = 0.023). Median OS and PFS did not differ significantly between groups. Cox regression showed that pulmonary metastasis (p = 0.019) was an independent prognostic factor for OS. RT (hazard ratio = 0.466, p = 0.005) and neutrophil-to-lymphocyte ratio (p = 0.001) were independently associated with PFS. Lymphocytopenia was more frequent in the RT group (p = 0.006), with no other significant differences in TRAEs.

Conclusion

RT combined with ICIs significantly improved ARR in MSS/pMMR mCRC, suggesting clinical benefit with a manageable toxicity profile and supporting further investigation of this combination.