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) until final overall survival data are available. High risk of recurrence was defined, as per protocol-criteria, as tumor stage II with nuclear grade 4 or sarcomatoid differentiation, tumor stage III 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.
The indication of adjuvant therapy is largely based on the pathologist's assessment of features such as; grade, sarcomatoid component, invasion of perinephric and/or sinus adipose tissue, and vascular invasion. In this review, we discuss the morphological and pathological features required to identity those patients harbouring a high-risk tumor, highlighting the issue related to interobserver variability and discuss tumor necrosis as additional prognostic parameter and the currently available prognostic scoring systems in ccRCC.
Pathologist assessment of prognostic features suffer 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. Moreover, the awareness of other morphological parameters such as architectural patterns may help pathologists in tumor grading. Application of molecular biomarkers may be useful tools in the near future to help clinicians identify patients harboring tumors with worse prognosis.
Expert review of anticancer therapy. 2022 Nov 15 [Epub ahead of print]
Alessia Cimadamore, Anna Caliò, Laura Marandino, Stefano Marletta, Carmine Franzese, Luigi Schips, Daniele Amparore, Riccardo Bertolo, Stijn Muselaers, Selcuk Erdem, Alexandre Ingels, Nicola Pavan, Angela Pecoraro, Önder Kara, Eduard Roussel, Umberto Carbonara, Riccardo Campi, Michele Marchioni, EAU-YAU Renal Cancer Working Group.
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy., Department of Diagnostic and Public Health, University of Verona., Department of Medical Oncology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, 20132 Milan, Italy., PhD Inflammation, Immunity and Cancer, University of Verona., Department of Urology, Polytechnic University of Marche, Ancona, Italy., Department of Medical, Oral and Biotechnological Science, "Ss. Annunziata" Hospital Urology Unit, "G. d'Annunzio" University of Chieti and Pescara, Chieti, Italy., Division of Urology, Department of Oncology, School of Medicine, San Luigi Hospital, University of Turin, Orbassano, Turin, Italy., Department of Urology, San Carlo Di Nancy Hospital, Rome, Italy., Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands., Division of Urologic Oncology, Department of Urology, Faculty of Medicine, Istanbul University, Istanbul, Turkey., Department of Urology, University Hospital Henri Mondor, Créteil, France., Urology Clinic, Department of Medical, Surgical and Health Science, University of Trieste, Trieste, Italy., Department of Urology, Kocaeli University School of Medicine, Izmit, Turkey., Department of Urology, University Hospitals Leuven, Leuven, Belgium., Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy., Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy.