Hot topics in renal cancer pathology: implications for clinical management

ABSTRACT

Introduction

The updated European Association of Urology (EAU) Guidelines issued a weak recommendation for adjuvant pembrolizumab for patients with high-risk operable clear cell Renal Cell Carcinoma (ccRCC). High risk of recurrence was defined, as per protocol-criteria, as T2 with nuclear grade 4 or sarcomatoid differentiation, T3 or higher, regional lymph node metastasis, or stage M1 with no evidence of disease. Considering the heterogeneous population included in the recommendation, it has been questioned if adjuvant pembrolizumab may lead to overtreatment of some patients as well as undertreatment of patients with worse prognosis.

Areas covered

In this review, we discuss the issues related to the assessment of pathological features required to identify those patients harboring a high-risk tumor, highlighting the issue related to interobserver variability and discuss the currently available prognostic scoring systems in ccRCC.

Expert opinion

PPathologist assessment of prognostic features suffers from interobserver variability which may depend on gross sampling and the pathologist’s expertise. The presence of clear cell feature is not sufficient criteria by itself to define ccRCC since clear cell can be also found in other histotypes. Application of molecular biomarkers may be useful tools in the near future to help clinicians identify patients harboring tumors with worse prognosis.

KEYWORDS:

• Renal cell carcinoma
• prognosis
• necrosis
• grade
• immunotherapy
• adjuvant therapy

Article highlights

• The updated European Association of Urology (EAU) Guidelines issued a weak recommendation for adjuvant pembrolizumab for patients with high-risk operable clear cell Renal Cell Carcinoma

• Among the high-risk criteria, pathological prognostic factors such nuclear grade 4 or sarcomatoid differentiation and tumor stage were included

• Reporting amount of grade 4 or sarcomatoid/rhabdoid component, percentage of tumor necrosis, equivocal vascular invasion or adipose tissue invasion are still object of debate among pathologists

• Pathologist assessment of prognostic features suffer from an interobserver variability which may depend on gross sampling and pathologist’s expertise

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

The authors have no funding to report.