Pathology and systemic therapy of non-clear cell renal cell carcinoma: an overview

ABSTRACT

Introduction: Non-clear cell renal cell carcinoma (nccRCC) represents a highly heterogenous group of kidney cancer entities. As most clinical trials predominantly include patients with clear cell RCC (ccRCC), nccRCC treatment guidelines are mainly extrapolated from recommendations in ccRCC. Here, we review and elucidate current data on the pathologic classification and treatment of nccRCC.

Areas covered: This article gives an overview of the WHO classification of RCC, showing the histological diversity of nccRCC and focusing particularly on entities first characterized since 2016, their specific molecular behavior and their role as indicators for hereditary cancer syndromes. In this context, we discuss the available data on nccRCC treatment oprtions such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, cytotoxic chemotherapy, and immune checkpoint inhibitors.

Expert opinion: Although nccRCCs are relatively uncommon, entities of this type account for a subgroup of up to 20–25% of all RCCs. Advances in histopathology and molecular genetics, together with evidence gained from retrospective and prospective clinical data, have improved understanding of these tumors in recent years. Nevertheless, selective trials of current and novel therapies including new targeted agents in patients with nccRCC are urgently needed to further improve treatment guidelines.

KEYWORDS:

• Immune checkpoint inhibitors
• non-clear cell renal cell cancer
• papillary renal cell cancer
• pathology
• therapy

Article highlights

• Overview of the WHO classification of RCC, showing the histological diversity of nccRCC

• Description of new nccRCC entities first characterized since 2016, their specific molecular and biological behavior, and their role as indicators for hereditary cancer syndromes

• Review of treatment outcomes in nccRCC, including targeted therapies; TKIs, mTOR inhibitors, and chemotherapy

• Recent data on new treatment options with immune checkpoint inhibitors as single agents and in combination with IO or TKI in nccRCC and RCC with sarcomatoid features

Declaration of interest

L Bergmann has served on the advisory boards for Pfizer, Ipsen EUSA, BMS, and Roche.

A Hartmann has received honoraria for lectures or consulting/advisory boards from; Abbvie, AstraZeneca, Biontech, BMS, Boehringer Ingelheim, Cepheid, Diaceutics, Illumina, Ipsen, Janssen, Lilly, MSD, Nanostring, Novartis, Qiagen, QUIP GmbH, Roche, 3DHistotech and other research support from AstraZeneca, Biontech, Cepheid, Illumina, Janssen, Nanostring, Qiagen, QUIP GmbH and Roche.

S Weber has received travel/congress expense assistance from Jazz Pharmaceuticals and IPSEN.

M Ahrens has served on the advisory boards for Pfizer, Ipsen, EUSA, BMS, and Merck.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.