Metastatic organ count stratifies survival in immunotherapy-treated metastatic colorectal cancer: a retrospective cohort study

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Abstract
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.

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