Chromophobe renal cell carcinoma: Long-term survival and treatment patterns from a real-world cohort.

467 Background: Chromophobe renal cell carcinoma (chRCC) is an uncommon subtype of renal cell carcinoma (RCC), representing approximately 5-10% of kidney cancers. It shows distinctive morphologic and molecular features and generally favorable prognosis, but evidence on managing advanced disease remains scarce. This study evaluated clinicopathologic features and outcomes of localized and metastatic chRCC in a real-world setting. Methods: We conducted a retrospective cohort study including patients (pts) diagnosed with chRCC at a single tertiary cancer center from 2009 to 2024. Clinical, pathological, and survival data were extracted from electronic records. Overall survival (OS) and disease-free survival (DFS) were estimated by Kaplan-Meier; prognostic factors were assessed by univariate analyses Cox proportional hazards mode, separately for pts with localized and advanced disease. Results: Among 2,181 RCC pts, 792 (36.3%) had non–clear cell histology, including 170 (7.8%) chRCC. Twenty-three had advanced disease ( de novo metastatic, n = 9; relapsed, n = 14). Median age at diagnosis was 58.5 years (Interquartile ratio IQR = 50.0-68.0); 54.1% were female, 95.2% had ECOG performance status 0 or 1. Stages were T1–T2 in 60% and T3–T4 in 40%. A second malignancy occurred in 21.2%, including 9 pts with another RCC and 4 with thyroid cancers. In the advanced cohort, most common metastatic sites were bone (56.5%) and lymph nodes (43.5%). Systemic therapy was administered to 55% of pts (pazopanib 6, sunitinib 4, sorafenib 1), with a response rate as per RECIST 1.1 of 18.2%. Metastasis-directed therapy (MDT) was employed in 60.8% (surgery 9, radiotherapy 5, multimodal 2). The 5-year OS for all pts was 83.8% (95% CI 77.4–90.8%), after a median follow-up of 60.9 months. Shorter OS was associated with M1 stage (p < 0.001), T3–T4 (p = 0.02), and ECOG ≥ 2 (p = 0.03). Among advanced cases, 5-year OS was 19% (95% CI 7–52%), and MDT correlated with improved survival (HR 0.22, 95% CI 0.07–0.69) in univariate analysis. No OS benefit was observed in pts who underwent cytoreductive nephrectomy (p = 0.9). For pts with localized disease, the 5-year DFS was 84% (95% CI 77–91%), with no significant associations between DFS and stage (p = 0.18), ECOG-PS (p = 0.49), or histological grade (p = 0.13). Conclusions: Advanced chRCC is associated with limited survival and suboptimal responses to systemic therapy. Notably, pts receiving MDT achieved improved outcomes, although this observation may reflect underlying selection bias.