Background <p>Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer, offering durable clinical benefits to a subset of patients. However, long-term survival is heterogeneous, and effective risk-stratification biomarkers for this subgroup are needed. This study investigated the prognostic significance of baseline serum uric acid (UA) levels in patients with dMMR/MSI-H colorectal cancer undergoing ICI therapy.</p> Patients and methods <p>This retrospective study enrolled 171 patients with advanced dMMR/MSI-H colorectal cancer receiving ICIs (monotherapy or combined with chemotherapy/targeted agents). Serum UA was measured within three days pre-treatment. An optimal UA cut-off was determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier estimates and Cox proportional hazards models assessed the UA-overall survival (OS) association.</p> Results <p>Median follow-up was 21.1 months (range: 1.2–48.0). ROC analysis identified an optimal serum UA threshold of 274 µmol/L (Area Under Curve (AUC) = 0.82; sensitivity = 70.0%; specificity = 70.8%). Patients with UA ≥ 274 µmol/L exhibited significantly shorter OS compared to those with lower UA (Hazard Ratio (HR) = 2.31; 95% CI: 1.04–6.12; <i>p</i> = 0.001). Multivariate analysis confirmed elevated UA as an independent predictor of poorer OS (HR = 2.73; 95% CI: 1.37–6.16; <i>p</i> = 0.015), alongside stage IV disease, concurrent use of multiple ICI agents and the use of immunotherapy in the ≥ 3rd-line setting.</p> Conclusion <p>Elevated baseline serum UA is associated with poorer long-term survival in patients with dMMR/MSI-H advanced colorectal cancer receiving immunotherapy. As an accessible and cost-effective biomarker, UA shows potential for early risk-stratification and guiding individualized treatment strategies within this immunotherapy-sensitive population.</p>

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Association between serum uric acid levels and clinical outcomes of immunotherapy in advanced colorectal cancer patients

  • Sufeng Fan,
  • Mingchen Shao,
  • Wang Ma

摘要

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer, offering durable clinical benefits to a subset of patients. However, long-term survival is heterogeneous, and effective risk-stratification biomarkers for this subgroup are needed. This study investigated the prognostic significance of baseline serum uric acid (UA) levels in patients with dMMR/MSI-H colorectal cancer undergoing ICI therapy.

Patients and methods

This retrospective study enrolled 171 patients with advanced dMMR/MSI-H colorectal cancer receiving ICIs (monotherapy or combined with chemotherapy/targeted agents). Serum UA was measured within three days pre-treatment. An optimal UA cut-off was determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier estimates and Cox proportional hazards models assessed the UA-overall survival (OS) association.

Results

Median follow-up was 21.1 months (range: 1.2–48.0). ROC analysis identified an optimal serum UA threshold of 274 µmol/L (Area Under Curve (AUC) = 0.82; sensitivity = 70.0%; specificity = 70.8%). Patients with UA ≥ 274 µmol/L exhibited significantly shorter OS compared to those with lower UA (Hazard Ratio (HR) = 2.31; 95% CI: 1.04–6.12; p = 0.001). Multivariate analysis confirmed elevated UA as an independent predictor of poorer OS (HR = 2.73; 95% CI: 1.37–6.16; p = 0.015), alongside stage IV disease, concurrent use of multiple ICI agents and the use of immunotherapy in the ≥ 3rd-line setting.

Conclusion

Elevated baseline serum UA is associated with poorer long-term survival in patients with dMMR/MSI-H advanced colorectal cancer receiving immunotherapy. As an accessible and cost-effective biomarker, UA shows potential for early risk-stratification and guiding individualized treatment strategies within this immunotherapy-sensitive population.