18th Meeting of the EAU Section of Oncological Urology (ESOU21)

ESOU 2021: Histological Classification and Immunophenotyping of Renal Tumors

(UroToday.com) The third renal cancer session at the 2021 European Association of Urology (EAU) Section of Oncological Urology (ESOU) Virtual Annual Meeting focused on the management of patients with advanced and metastatic disease. In this session, Dr. Holger Moch presented on the histological classification and immunophenotyping of renal tumors.

Dr. Moch began by discussing the 2016 World Health Organization (WHO) classification of malignant epithelial renal tumors, of which there are 14 types, despite the fact that clinical practice focused on clear cell, papillary, and chromophobe.

Clear cell renal cell carcinoma (ccRCC) is the predominant subtype clinically and thus forms the preponderance of disease treated on trials. Dr. Moch highlighted that differing phenotypes of these tumors (hypervascular, immunogenic, and metabolic) lend differing sensitivity to a variety of systemic therapy approaches. The remaining “non-clear-cell” subtypes have many fewer evidence-based treatment options.

Dr. Moch emphasized that there are no predictive biomarkers in renal cell carcinoma. However, there is significant ongoing work (including the TRACERx Renal study) to define tumor types based on their driver events. Further work has similarly supported molecularly subtyping of advanced renal cell carcinoma into seven groups on the basis of transcriptomics, somatic alterations, and PD-L1 expression. Based on their characteristics, some tumors are expected to respond best to immune checkpoint inhibition while others are expected to respond best to anti-angiogenic treatments. Work from Brugarolas and colleagues demonstrated underlying driver mutations associated with these subtypes.

Dr. Moch then posed the question of how we can stratify patients who will benefit from novel immunotherapeutic approaches. Moving forward, he suggested that pathologists will likely be able to provide further detail in order to guide treatment decision making.

In particular, he emphasized that patients with “non-inflamed” (or immune-desert) tumors are not expected to benefit from checkpoint inhibition. Thus, a more detailed pathologic assessment may allow for more targeted patient treatment recommendations.

In addition to this characterization of the tumor, Dr. Moch discussed the role of imaging mass cytometry to characterize the tumor microenvironment. Based on work led by Dr. Bodenmiller, 17 different tumor-associated macrophage phenotypes were identified in patients with ccRCC. These different phenotypes have both prognostic information and are associated with differential response to treatment.

Dr. Moch highlighted that the large bulk of data presents a difficult job for those attempting to create a unified, yet comprehensible, classification schema. Given the genomic heterogeneity of morphologically similar tumors, he suggested that molecularly-defined renal cell carcinoma may be the way forward.

Presented by: Holger Moch, MD, Professor of Pathology, Chairman of the Institute of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland

Written by: Christopher J.D. Wallis, MD, PhD, FRCSC, Instructor in Urology, Vanderbilt University Medical Center, Nashville, Tennessee, Twitter: @WallisCJD during the 18th Meeting of the EAU Section of Oncological Urology (ESOU21), January 29-31, 2021

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