ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmune landscape and therapeutic barriers in gastrointestinal cancersView all articles
Metastatic Organ Count Stratifies Survival in Immunotherapy-Treated Metastatic Colorectal Cancer: A Retrospective Cohort Study
Provisionally accepted
- Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
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Background: Immunotherapy for metastatic colorectal cancer (mCRC) leads to varying patient outcomes owing to the heterogeneity of metastatic organs. However, whether the metastatic organ count influences prognosis in mCRC patients receiving immunotherapy remains unclear. Therefore, this retrospective study aimed to investigate this issue to derive a clear conclusion to facilitate clinical treatment. Methods: This retrospective cohort study included 208 patients with mCRC receiving immunotherapy at the Sun Yat-sen University Cancer Center. Cox regression analysis was conducted to determine variables independently associated with immunotherapy response and progression-free survival (PFS). The Kaplan–Meier curve analysis and log-rank test were used to evaluate PFS across varying metastatic organ counts. Subsequently, a nomogram was constructed for PFS prediction. Results: Patients with varying metastatic organ counts exhibited significantly different objective response rates (ORRs) (1 to ≥4 organs: 49.3%, 30.0%, 19.6%, 5.9%, respectively, P<0.001). Multivariable Cox analysis identified low tumor mutational burden (hazard ratio [HR]=2.49, 95% confidence interval [CI]: 1.60–3.88, P<0.001), second-or-higher-line immunotherapy (HR=2.83, 95% CI: 1.81–4.44, P<0.001), and high metastatic organ counts (3 organs: HR=2.21, 95% CI: 1.40–3.51, P=0.001; ≥4 organs: HR=3.85, 95% CI: 2.06–7.22, P<0.001) as independent factors associated with low PFS time. Additionally, patients with lung metastasis had a markedly lower ORR (14.6%) than did others (distant lymph node [30.7%], liver [30.3%], peritoneum [29.5%]; P<0.001). Conclusions: Increased metastatic organ count in patients with mCRC was associated with decreased immunotherapy ORR and worse prognosis, with a particularly pronounced effect observed in patients with lung metastasis.
Keywords: Metastatic organ count, Metastatic colorectal cancer, Immunotherapy, prognosis, Lung metastasis
Received: 04 Aug 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Fu, Zhang, Wang, Huang, Tian, Wang, Bai and Wang. 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:
Na Wang
Kunhao Bai
Zhiqiang Wang
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