Understanding Pathologic Variants of Renal Cell Carcinoma: Distilling Therapeutic Opportunities from Biologic Complexity

Abstract

Context

Once believed to represent a uniform malignant phenotype, renal cell carcinoma (RCC) is now viewed as a diverse group of cancers that arise from the nephron.

Objective

To review the pathologic characteristics, clinical behavior, molecular biology, and systemic therapy options of recognized RCC histologic subtypes.

Evidence acquisition

A systematic review of English-language articles was performed using the Medline and Web of Science databases. Manuscripts were selected with consensus of the coauthors and evaluated using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria.

Evidence synthesis

The major findings of the evaluated manuscripts are discussed with an emphasis on the description of the pathologic features, clinical behavior, prognosis, and therapeutic strategies.

Conclusions

Classification schemes for kidney cancer have undergone dramatic changes over the past two decades. Improvements in these classification schemes are important, as pathologic variants differ not only in disease biology, but also in clinical behavior, prognosis, and response to systemic therapy. In the era of genomic medicine, further refinements in characterization of RCC subtypes will be critical to the progress of this burgeoning clinical space.

Patient summary

Kidney cancer can be subdivided into related but different cancers that arise from the kidney's tubules. In this article we review current classifications for kidney cancer, discuss their characteristics, and provide an overview of each subtype's clinical behavior and treatment. We stress that each subtype harbors unique biology and thus responds differently to available treatment strategies.

Introduction

Renal cell carcinoma (RCC) has emerged as one of the most rapidly evolving areas of solid tumor oncology. The past two decades have seen a dramatic change in the clinical landscape that shapes both RCC understanding and treatment. Development of minimally invasive techniques for surgery in the retroperitoneum, emergence of focal therapy, reemergence of percutaneous renal biopsy, introduction of active surveillance strategies, renewed interest in immunotherapy, and the clinical development of targeted therapies for patients with advanced disease have all revolutionized kidney cancer care. Nevertheless, arguably, one of the most significant paradigm shifts in the clinical constructs that shape kidney cancer care is the change in the pathologic classification of RCC (Fig. 1). Efforts aimed at morphologically grouping specific cancers into distinct pathologic subtypes have not only allowed a common descriptive language, but are helping to crystallize the understanding of RCC's molecular origins and its clinical behavior. Indeed, these improved insights into the similarities and differences among RCC variants should offer clinical and therapeutic opportunities to improve patient care.