Advanced Non-Clear Cell Renal Cell Carcinoma Treatments and Survival: A Real-World Single-Centre Experience

SIMPLE SUMMARY: Non-clear cell renal cell carcinoma (nccRCC) represents about the 20% of all RCCs but recommendations on treatment lacks evidence since the clinical trials include only clear cell RCC (ccRCC). The aim of our retrospective studies was to evaluate the efficacy of TKI and immunotherapy-based combinations in this population. We confirmed that nccRCC are heterogeneous and have a poorer prognosis as compared to ccRCC. The introduction of immunotherapy increased the efficacy of the treatments and the survival outcomes. Prognostic factors such as IMDC score or NLR are valid also for nccRCC. We highlight the importance of a pathological review and the need for prospective randomized trials designed for the different subtypes. ABSTRACT: Background: Non-clear cell renal cell carcinoma (nccRCC) is a heterogeneous group of cancer. Treatment recommendations are extrapolated from ccRCC and lack solid evidence. Here, we review advanced nccRCC patients treated at our institute. Patients and methods: We collected retrospective data on all advanced nccRCC pts treated at the Istituto Oncologico Veneto from January 2008. We compared overall response rate (ORR), progression free survival (PFS) and overall survival (OS) according to histological subtypes and type of systemic treatments. Kaplan-Meier method, log-rank test and Cox regression were used to estimate and compare PFS and OS. Results: Of 1370 RCC patients, 289 had a diagnosis of nccRCC and 121 were eligible for the analysis. Fifty-three pts showed papillary histology (pRCC), 15 chromophobe; 37 unclassified RCC (NOS-RCC), 16 other histologies. Pts with chromophobe and other hystologies showed poorer survival rates compared to pRCC and NOS-RCC (mOS 10.7 vs. 20.7 vs. 30.7, p = 0.34). Pts treated with combination regimens achieved a better OS (30.7 vs. 13.7, p = 0.10), PFS (12.7 vs. 6.4, p = 0.10) and ORR (42.4% vs. 13.9%, p = 0.002) than those treated with monotherapy. IMDC and Meet-URO score retained their prognostic value. Conclusion: Our retrospective real-life cohort of advanced nccRCC patients shows that immunotherapy-based combinations could improve ORR, PFS and OS compared to TKI monotherapy. Prospective trials for nccRCC patients utilizing novel therapies are ongoing and their results eagerly awaited.