title: Sarcomatoid dedifferentiation in metastatic clear cell renal cell carcinoma and outcome on treatment with anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors: a retrospective analysis.
abstract: BACKGROUND
  This study aimed to assess the efficacy of anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGFR-TKIs) in patients with metastatic clear cell renal cell carcinoma (m-ccRCC) with sarcomatoid dedifferentiation.
  
  
  METHODS
  The files of all patients with m-ccRCC consecutively treated with first-line anti-VEGFR-TKIs at the authors' institution were retrospectively reviewed. Pathology slides from nephrectomy and metastasectomy were assessed for the presence and extent of sarcomatoid dedifferentiation.
  
  
  RESULTS
  A total of 124 patients were included; nephrectomy and metastasectomy specimens were available in 117 and 35 patients, respectively. Thirty percent of the primary nephrectomy specimens had sarcomatoid features, and the median involvement of the sarcomatoid component was 21% (range, 1%-95%). Patients with an important sarcomatoid component, defined as ≥ 25% involvement of the tumor, had a very poor outcome: progression-free survival (PFS) and overall survival (OS) were 3 and 6 months, respectively, and no partial responses (PR) were observed. Patients without sarcomatoid dedifferentiation or with sarcomatoid involvement < 25% had a PFS of 12 months (P < .0001; hazard ratio [HR], 51; 95% CI, 12.58-207.3), an OS of 22 months (P < .0001, HR, 10.72; 95% CI, 3.56-32.25), and a PR rate of 50% (P = .0015). Patients with a sarcomatoid component ≥ 25% in the metastasectomy also had a poorer PFS and OS on anti-VEGFR-TKIs compared with patients with < 25% of sarcomatoid features at these sites.
  
  
  CONCLUSIONS
  Patients with m-ccRCC whose tumors contain a component of sarcomatoid dedifferentiation of ≥ 25% of the total tumor volume have a very poor outcome when treated with anti-VEGFR-TKIs. Analysis of the extent of sarcomatoid features in resected metastases can provide additional prognostic information.
authors.affiliation: General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven. Electronic address: benoit.beuselinck@uzleuven.be.
authors.forename: Benoit
authors.initials: B
authors.lastname: Beuselinck
authors.affiliation: Pathology, University Hospitals Leuven, Department of Imaging and Pathology, KU Leuven.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.affiliation: General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven.
authors.forename: Pascal
authors.initials: P
authors.lastname: Wolter
authors.affiliation: General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven.
authors.forename: Herlinde
authors.initials: H
authors.lastname: Dumez
authors.affiliation: Urology, University Hospitals Leuven, KU Leuven.
authors.forename: Johannes
authors.initials: J
authors.lastname: Berkers
authors.affiliation: Urology, University Hospitals Leuven, KU Leuven.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.affiliation: Urology, University Hospitals Leuven, KU Leuven.
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
authors.affiliation: Radiology, University Hospitals Leuven, Department of Imaging and Pathology, KU Leuven.
authors.forename: Raymond
authors.initials: R
authors.lastname: Oyen
authors.affiliation: Radiology, University Hospitals Leuven, Department of Imaging and Pathology, KU Leuven.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: De Wever
authors.affiliation: General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven.
authors.forename: Michiel
authors.initials: M
authors.lastname: Strijbos
authors.affiliation: General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven.
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.affiliation: General Medical Oncology and Laboratory for Experimental Oncology, University Hospitals Leuven, Leuven Cancer Institute, KU Leuven.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schöffski
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077784:Axitinib; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation / Q000187:drug effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007191:Indazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology / Q000601:surgery; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D009536:Niacinamide; D000068258:Bevacizumab; C516667:pazopanib; D000077157:Sorafenib; D000077784:Axitinib; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib
keywords: Targeted therapy; anti-angiogenics; epithelial-to-mesenchymal transition; kidney tumors; prognostic marker