Clinicopathological characteristics and prognosis of metastatic non-clear cell renal cell carcinoma.

Abstract

504 Background: Non-clear cell renal cell carcinoma (nccRCC) is a clinicopathological heterogeneous disease that comprises a complex mixture of different pathology subtypes, accounting for approximately 20% of all RCC cases. Due to its heterogeneity and rarity, standard treatment strategy for metastatic nccRCC remain poorly defined. Methods: We conducted retrospective analysis of 105 metastatic nccRCC patients at our center from June 2010 to April 2022. Demographic, clinicopathological, and systemic therapy data were collected. The data of 872 metastatic ccRCC patients were also collected for comparison.The end points included progression-free survival (PFS) and overall survival (OS). Results: Among 105 metastatic nccRCC patients, the most prevalent histology was papillary RCC (pRCC, 39.0%). The second most common histological type was translocation RCC (tRCC, 29.5%), followed by unclassified RCC (24.8%). The median age of metastatic nccRCC patients was 50 years old. 68.6% patients had advanced primary tumor stage of T3/4, and 48.6% patients had regional lymph node metastasis. The most common distant metastasis site was lung metastasis (52.4%), followed by bone metastasis (33.3%), and 21.0% patients had liver metastasis. The proportion of the favorable, intermediate, and poor IMDC risk group were 19.0%, 54.3%, and 26.7%, respectively. Among metastatic nccRCC patients, 26 received first-line IO-TKI therapy, 79 received first-line TKI monotherapy therapy. During the median follow-up of 22.2 months, there was no statistical significance between the prognosis of IO-TKI and TKI monotherapy group (PFS: 10.9 months vs. 8.6 months, P = 0.23; OS: 23.3 months vs. 24.0 months, P = 0.39). The PFS of tRCC was significantly longer than pRCC and unclassified RCC (P＜0.001). According to the Cox regression model, unclassified RCC pathology (HR=2.027，P=0.023) and poor IMDC risk group (HR=2.285，P=0.011) were identified as the independent risk factors for PFS. Poor IMDC risk group was also identified as the independent risk factors for OS (HR=2.638，P=0.007). Compared to metastatic ccRCC, the metastatic nccRCC patients were younger, with more advanced T and N stage, having a higher proportion for liver metastasis. The outcome of metastatic nccRCC was also poorer than metastatic ccRCC patients (P＜0.001), with a median OS of 24.0 months and 38.0 months, respectively. Conclusions: Compared to metastatic ccRCC, the prognosis of the patients with metastatic nccRCC was poorer, and the metastatic nccRCC patients were younger, with more advanced T and N stage, having a higher proportion for liver metastasis. Unclassified RCC pathology and poor IMDC risk group were the independent risk factors for poor prognosis. For metastatic nccRCC, the efficacy of IO-TKI was not superior than TKI monotherapy.Therefore, it is of great significance to investigate novel therapeutic targets for metastatic nccRCC.