Oncological Outcomes of Non-clear Cell Renal Cell Carcinomas: A Retrospective Study From a Tertiary Care Center

Background Non-clear cell renal cell carcinomas (nccRCCs) are a histologically heterogeneous and clinically underrepresented group of renal malignancies, distinct from clear cell RCC in morphology, molecular profile, and prognosis. Despite accounting for 20-30% of RCCs, nccRCC subtypes are infrequently studied, especially in the Indian population. This study aimed to evaluate the clinicopathological features, immunohistochemical patterns, and oncological outcomes of primary nccRCCs in a tertiary care setting. Methods This was a retrospective, single-center study including 37 adult patients diagnosed with histologically confirmed nccRCC between January 2015 and December 2024. Subtypes analyzed included papillary RCC, chromophobe RCC, collecting duct carcinoma, Xp11.2 translocation RCC, mucinous tubular and spindle cell carcinoma (MTSCC), unclassified RCC, and other rare variants. Demographic, clinical, pathological, and immunohistochemical (IHC) data were evaluated. Kaplan-Meier analysis was used to estimate disease-free survival (DFS) and overall survival (OS), with comparisons between subtypes made using the log-rank test and Chi-square/Fisher's exact test. Results The cohort had a mean age of 54.3 ± 11.2 years and was predominantly male (67.6%). Papillary RCC (37.8%) and chromophobe RCC (21.6%) were the most common subtypes. Collecting duct carcinoma exhibited significantly higher rates of distant metastasis (80%, p = 0.014) and mortality (80%, p = 0.005), confirming its aggressive nature, as observed in prior studies. Median DFS and OS were 19 months (IQR: 12-36) and 31 months (IQR: 18-48), respectively. Five-year survival was highest for chromophobe RCC (87.5%) and lowest for collecting duct carcinoma (0%, p = 0.001). CK7 and CD117 were highly expressed in papillary and chromophobe RCCs, respectively, aiding subtype identification. The overall mortality rate was 37.8%. The small sample size and single-institution scope were key limitations. Conclusion This study demonstrates the prognostic variability among nccRCC subtypes, with papillary and chromophobe RCC showing relatively favorable outcomes, and collecting duct carcinoma associated with poor survival. Histological subtype remains the cornerstone of prognosis and therapeutic decision-making. Subtype-specific management strategies, early recognition through IHC, and incorporation of molecular profiling are essential to optimize outcomes. Larger, multicentric prospective studies are warranted to validate these findings and improve clinical guidance in resource-limited settings.