IUC26678-94 Impact of Metastatic Patterns on First-Line Therapy in mRCC: Meet-URO 33

Abstract Background Metastatic site is a well-recognized prognostic factor in metastatic renal cell carcinoma (mRCC). Endocrine metastases, particularly to the pancreas and thyroid, are associated with favorable outcomes, whereas bone, liver, and brain metastases are linked to poorer prognosis. However, whether these metastatic patterns influence first-line treatment selection remains unclear. Methods Meet-URO 33 is an ongoing Italian multicenter retrospective/prospective observational study including patients with mRCC treated with first-line immune checkpoint inhibitor plus immune checkpoint inhibitor (ICI–ICI), immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI–TKI), or tyrosine kinase inhibitor (TKI) monotherapy. Patients were classified as having favorable-prognosis metastases (pancreatic and/or thyroid only) or poor-prognosis metastases (bone, liver, and/or brain only). Associations between metastatic patterns, treatment selection, progression-free survival (PFS), and overall survival (OS) were assessed. Results Among 2,027 enrolled patients, 189 (9%) had favorable-prognosis metastases (pancreas 8%, thyroid 1%), while 1,022 (50%) had poor-prognosis metastases (bone 30%, liver 15%, brain 5%). Patients with favorable-prognosis metastases more frequently received first-line TKI monotherapy than ICI–TKI or ICI–ICI (17% vs. 10% vs. 3%; p<0.001). Conversely, patients with poor-prognosis metastases were more commonly treated with ICI–TKI than ICI–ICI or TKI alone (50% vs. 38% vs. 33%; p<0.001). On multivariable analysis, favorable-prognosis metastases were independently associated with improved OS (HR 0.34, 95% CI 0.19–0.61; p<0.001) and PFS (HR 0.53, 95% CI 0.37–0.76; p<0.001), whereas poor-prognosis metastases were independently associated with worse OS (HR 1.32, 95% CI 1.11–1.57; p = 0.002) and PFS (HR 1.20, 95% CI 1.04–1.38; p = 0.013). Conclusions Favorable- and poor-prognosis metastatic patterns are associated with distinct survival outcomes and different first-line treatment choices in mRCC. Although the observational design precludes causal inference, TKI-based strategies appear to play a central role in both settings. TKI monotherapy is more frequently used in patients with favorable-prognosis metastases, likely reflecting their indolent and angiogenic biology, whereas ICI–TKI combinations are preferred in poor-prognosis disease, where tumor shrinkage and disease control are priorities. Prospective studies are warranted to determine the predictive value of these metastatic patterns across different treatment strategies.