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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, = 0.34). Pts treated with combination regimens achieved a better OS (30.7 vs. 13.7, = 0.10), PFS (12.7 vs. 6.4, = 0.10) and ORR (42.4% vs. 13.9%, = 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.
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http://dx.doi.org/10.3390/cancers15174353 | DOI Listing |
Beijing Da Xue Xue Bao Yi Xue Ban
August 2025
Department of Urology, Peking University Third Hospital, Beijing 100191, China.
Objective: To compare the clinicopathological characteristics and prognostic outcomes between patients with clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC) accompanied by venous tumor thrombus.
Methods: A retrospective analysis was conducted on clinical and pathological data from patients with RCC and venous tumor thrombus treated in the Department of Urology at Peking University Third Hospital between January 2014 and February 2024. Patients were stratified into two groups based on pathological type: ccRCC and nccRCC.
Eur Urol
July 2025
Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Background And Objective: Initial results from the KEYNOTE-B61 trial demonstrated that pembrolizumab combined with lenvatinib has promising antitumor activity in previously untreated advanced non-clear-cell renal cell carcinoma (nccRCC). We report updated efficacy and safety results after nearly 2 yr of follow-up.
Methods: The single-arm, multicenter, phase 2 KEYNOTE-B61 trial enrolled patients aged ≥18 yr with previously untreated advanced nccRCC.
JAMA Oncol
July 2025
Oncology Unit, ASST Bergamo ovest, Treviglio (BG), Italy.
Importance: Non-clear cell renal cell carcinomas (nccRCCs) present considerable challenges owing to their heterogeneity and limited clinical trial representation. Understanding the benefits of combining immunotherapy and targeted therapy for these subtypes is crucial for improving patient outcomes.
Objective: To evaluate the efficacy of various first-line immunotherapy combinations and targeted therapy in treating metastatic nccRCC.
Ther Adv Med Oncol
June 2025
Genitourinary Medical Oncology Program, Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365B Clifton Road NE, Suite B4000, Office 4212, Atlanta, GA 30322, USA.
Non-clear cell renal cell carcinomas (nccRCC) comprise a heterogeneous group of rare malignancies, accounting for approximately 20% of all kidney cancers. Given the rarity of these diverse subsets of RCC, the treatment paradigm for nccRCC is often based on treatment strategies utilized in the management of clear cell renal cell carcinoma (ccRCC), which may not fully address the distinct molecular and genetic drivers unique to nccRCC tumors. However, recent advances in the molecular characterization of nccRCC have led to the identification of new therapeutic targets, resulting in the development of more targeted therapies for nccRCC treatment.
View Article and Find Full Text PDFJ Hematol Oncol
May 2025
Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute, Department of Urology, Fudan University Shanghai Cancer
Papillary renal cell carcinoma (pRCC), a main pathological subtype of non-clear cell RCC (nccRCC), has strong heterogeneity. Comparing to other nccRCC subtypes, advanced pRCC has the poorest prognosis. Due to its lower incidence compared to ccRCC, clinical research and exploration of non-invasive biomarkers for pRCC are limited, and it is often misclassified.
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