Metastatic Clear-cell Renal Cell Carcinoma With a Long-term Response to Sunitinib: A Distinct Phenotype Independently Associated With Low PD-L1 Expression.

Long-term responders (LTRs) are defined by at least 18 months of response to sunitinib in metastatic clear-cell renal cell carcinoma (ccRCC). Well-described by clinical studies, the phenotype of these tumors has never been explored.

In a retrospective and multicenter study, 90 ccRCCs of patients with metastatic disease were analyzed. Immunohistochemistry (carbonic anhydrase IX, vascular endothelial growth factor, c-MET, programmed death-ligand 1 [PD-L1], and PD-1) and VHL status were performed. Progression-free survival and overall survival were calculated from sunitinib introduction and from progression. LTRs and their corresponding tumors were compared with others using univariate and multivariate analysis.

Twenty-eight patients were LTRs. They had a median progression-free survival of 28 months versus 4 months for other patients (P < .001). Similarly, LTRs had a median overall survival of 49 months versus 14 months (P < .001), even from progression (median, 21 vs. 7 months; P = .029). They were associated with a favorable or intermediate risk (International Metastatic Renal Cell Carcinoma Database Consortium model) (P = .007) and less liver metastasis (P = .036). They experienced more frequent complete or partial responses at the first radiologic evaluation (P = .035). The corresponding ccRCCs were associated with less nucleolar International Society for Urological Pathology grade 4 (P = .037) and hilar fat infiltration (P = .006). They were also associated with low PD-L1 expression (P = .02). Only the International Metastatic Renal Cell Carcinoma Database Consortium model and PD-L1 expression remained significant after multivariate analysis (P = .014 and P = .029, respectively).

Primary tumor characteristics of LTRs were studied for the first time and demonstrated a different phenotype. Interestingly, they were characterized by low expression of PD-L1, suggesting a potentially lower impact of targeted immunotherapy in these patients.

Clinical genitourinary cancer. 2019 Feb 04 [Epub ahead of print]

Solène-Florence Kammerer-Jacquet, Angelique Brunot, Mathilde Lefort, Sahar Bayat, Benoit Peyronnet, Gregory Verhoest, Romain Mathieu, Alexandra Lespagnol, Jean Mosser, Brigitte Laguerre, Alain Ravaud, Jean-Christophe Bernhard, Frantz Dupuis, Mokrane Yacoub, Marc-Antoine Belaud-Rotureau, Karim Bensalah, Nathalie Rioux-Leclercq

Service d'Anatomie et Cytologie Pathologiques, Université de Rennes 1, Université Bretagne Loire, Rennes, France; Unité Mixte de Recherche 6290-Institut de Génétique et Développement de Rennes, Rennes, France. Electronic address: ., Service d'Oncologie Médicale, Centre Eugène Marquis, Rennes, France., Ecole des Hautes Etudes en Santé Publique, Rennes, France., Service d'Urologie, Université de Rennes 1, Université Bretagne Loire, Rennes, France., Service de Génétique Somatique des Cancers, Université de Rennes 1, Université Bretagne Loire, Rennes, France., Service d'Oncologie Médicale, Centre Hospitalier Universitaire Saint-André, Bordeaux, France., Service d'Urologie, Centre Hospitalier Universitaire Pellegrin, Bordeaux, France., Service d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire Pellegrin, Bordeaux, France., Unité Mixte de Recherche 6290-Institut de Génétique et Développement de Rennes, Rennes, France; Service de Cytogénétique, Université de Rennes 1, Université Bretagne Loire, Rennes, France., Service d'Anatomie et Cytologie Pathologiques, Université de Rennes 1, Université Bretagne Loire, Rennes, France; Unité Mixte de Recherche 6290-Institut de Génétique et Développement de Rennes, Rennes, France.

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