Association between site of metastases and survival stratification of the IMDC classification in metastatic renal cell carcinoma (mRCC).

566 Background: The IMDC risk model is pivotal for prognostic stratification of mRCC, dividing patients into favorable (FAV), intermediate (INT) and poor-risk (POOR) groups with distinct overall survival (OS) estimates. While valuable for treatment decisions in first line, IMDC does not encompass sites of metastasis, potentially missing a significant prognostic factor. Methods: We retrospectively included mRCC patients receiving first-line therapy at Niguarda Cancer Center, Milan, Italy from 2008 to 2024. The primary aim was to evaluate if specific metastatic sites could redefine IMDC prognostic stratification. OS was analyzed using Kaplan-Meier estimates. Univariate and multivariate Cox regression analyses were performed including variables in the table. Results: 164 patients were eligible for analysis. Bone, liver and nodal metastases were independent negative prognostic factors both in univariate and multivariate analyses (HR 2.83, IC95% 1.78-4.49, p<0.001; HR 1.79, IC95% 1.12-2.85, p=0.014; HR 1.92, IC95% 1.28-2.88, p=0.002, respectively). As expected, FAV IMDC and first-line immunotherapy-based combinations (IO-IO or IO-TKI) were positive prognostic factors (both p<0.001). Having at least one bone and/or liver and/or nodal metastasis (B/L/N) was significantly associated with poorer prognosis and could re-stratify INT IMDC patients into two subpopulations with different OS (HR 1.88, p=0.046): B/L/N-positive INT OS rates were not different from POOR (p=0.193) and B/L/N-negative INT OS rates were comparable to FAV (p=0.193). Conclusions: B/L/N metastases are independent prognostic factors in mRCC, despite being unaddressed by IMDC. Present findings align with prior research supporting the inclusion of metastatic sites in prognostic scores. IMDC classification could be refined with inclusion of metastatic sites to improve prognostic accuracy. Patient characteristics. Age ≥50 147 (90) Sex Male 123 (75) IMDC FAV 42 (26) INT 85 (52) POOR 37 (22) Site of metastasis Bone 40 (24) Liver 31 (19) Nodal 85 (52) Oligometastases (<4) 33 (20) First-line immunotherapy-based combinations 38 (23) Data are shown as number of patients (N) and, within brackets, percentage (%).