Modified Glasgow prognostic score predicts outcomes of tyrosine kinase inhibitor monotherapy and immune checkpoint inhibitor combination therapy for metastatic renal cell carcinoma

Tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) are standard treatments for metastatic renal cell carcinoma (mRCC). the modified Glasgow prognostic score (mGPS) was suggested as one of promising biomarkers. This study evaluated the clinical utility of mGPS in patients with mRCC receiving TKI and ICI therapy and investigated the differential impact of TKI monotherapy and ICI combination therapy on treatment outcomes. We retrospectively analyzed 265 patients with mRCC treated at Hiroshima University and its affiliated hospitals between 2007 and 2023. Patients were stratified according to mGPS (low: score 0; high: score 1, 2) and treatment modality (TKI monotherapy or ICI combination therapy). Overall survival (OS) was analyzed using the Kaplan-Meier method and multivariate Cox regression models. The clinical utility of mGPS was assessed using decision curve analysis. A high mGPS was associated with aggressive disease features and poor prognosis. Multivariate analysis identified mGPS as an independent predictor of OS (HR = 2.101, 95% CI: 1.082-4.078, P = 0.028). Its discriminative ability was comparable to that of the IMDC criteria (C-index: 0.681 vs. 0.682) while providing a superior net benefit, especially within the threshold probability range of 0.30-0.65. In the high-mGPS group, ICI combination therapy significantly improved OS compared to TKI monotherapy (median: 25.4 vs. 8.6 months, P = 0.011). The mGPS effectively predicted the oncological outcomes for mRCC. In particular, it may help identify patients with high mGPS who could benefit from ICI combination therapy.