Defining and Prognosticating nccRCC: Constant Molecular Evolution

A roundtable discussion, moderated by Laurence Albiges, MD, PhD, discussed the risk stratification and management of metastatic non-clear cell renal cell carcinoma (nccRCC), along with recent advancements in targeted therapies and immuno-agents, treatment sequencing and combination approaches, and adjuvant therapy options. Dr. Albiges was joined by Renée Maria Saliby, MD, MSc; Tian Zhang, MD; and Shahla Bari, MD.

In the first segment of the roundtable series, the panel explores the evolution of our understanding of nccRCC, discussing its classification, molecular distinctions, and prognostic criteria.

View the next segment on Managing Metastatic nccRCC: Historical Approaches and Current Changes.

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Dr. Albiges: Welcome to GU Oncology Now. My name is Laurence Albiges, and I am a medical oncologist and Professor of Medical Oncology at Gustave Roussy Cancer Institute in France, the largest cancer center in Europe. Today, we will be discussing the treatment and management of patients with nccRCC. I am delighted to welcome my 3 guests. I will let them introduce themselves before we kick off our discussion.

Dr. Zhang: I am Tian Zhang, a GU medical oncologist and Associate Director for Clinical Research at the Harold C. Simmons Comprehensive Cancer Center and UT Southwestern Medical Center in Dallas, Texas.

Dr. Bari: My name is Shahla Bari, and I am a physician scientist and GU medical oncologist at Duke Cancer Institute. My lab and clinical practice focus on renal cell cancer.

Dr. Saliby: I am Renée Saliby. I have been a postdoc research fellow at Dana-Farber for the last 3 years, and I am now a first-year resident in internal medicine at Yale/New Haven Hospital.

Dr. Albiges: Excellent. Thank you all. Without further ado, let us start our discussion on nccRCC.

Dr. Bari: As we know, 75% to 80% of renal cell cancer is clear cell RCC. The remaining 20% is nccRCC, encompassing various histologies. Among them, the most common are papillary cell RCC, medullary RCC, collecting duct RCC, chromophobe RCC, and translocation RCC. These classifications are based on World Health Organization (WHO) guidelines updated in 2016.

Papillary cell RCC has been historically sub-classified into type 1 and type 2, though this distinction is now phasing out. This is where we stand in nccRCC.

Dr. Albiges: This field is constantly evolving as we define new entities. We now have molecularly defined entities in the WHO classification, improving our understanding of these subsets among nccRCC.

Dr. Bari: Absolutely. For example, in papillary cell RCC, many are MET-driven, leading to different treatment options. We are moving towards more molecular-based divisions rather than anatomical classifications.

Dr. Albiges: That is why some people prefer the term “variant histologies” instead of non-clear cell, as these are clearly different entities. Hopefully, we will develop different treatments for them. Now, regarding the prognosis of nccRCC?

Dr. Bari: Good point. In clear cell RCC, the Memorial Sloan Kettering Cancer Center (MSKCC) criteria and International Metastatic RCC Database Consortium (IMDC) criteria are well validated for prognostication. Similarly, for nccRCC, the IMDC and MSKCC criteria are valid, although less so in the immunotherapy era. For advanced RCC, global RCC criteria and venous criteria have better prognostic accuracy in variant histologies, especially papillary cell RCC.

Advanced global RCC prognostic criteria, which include factors like LDH and metastasis, have a 77% sensitivity. Another group has developed venous growth stratification, including TNM staging, venous thrombosis, and nuclear grading, to classify papillary cell RCC into low, intermediate, and high recurrence risk, with a 75% prognostic accuracy.

Dr. Albiges: So, there have been advances in prognostic assessments, but in metastatic settings, we can use the IMDC criteria.

Dr. Bari: Absolutely. The IMDC criteria are applicable for both clear cell and nccRCC.