title: Effect of glandular metastases on overall survival of patients with metastatic clear cell renal cell carcinoma in the antiangiogenic therapy era.
abstract: BACKGROUND
  Glandular metastases (GMs) (pancreas, breast, parotid, thyroid, or contralateral adrenal) are rare in metastatic clear cell renal cell carcinoma (mccRCC). In a multicenter study we have assessed outcome from mccRCC with or without GMs.
  
  
  METHODS
  Patients with mccRCC and GM or non-GM (NGM) at first presentation of mccRCC, treated at 9 European centers (5 French, 3 UK, and 1 Belgian centers) between January 2004 and October 2013, were retrospectively analyzed. Association between overall survival (OS) and site of metastases was assessed using the log-rank test for univariate analysis and the chi-square test for multivariable Cox regression.
  
  
  RESULTS
  In all, 138 patients with GM mccRCC and 420 with NGM mccRCC were included; 37.2% patients with GM had Memorial Sloan-Kettering Cancer Center (MSKCC)-favorable risk vs. 18% NGM patients; 10.7% patients with GM had MSKCC-poor risk vs. 27% NGM patients (P<0.0001). Median interval from metastases to treatment was 4.2 months (range: 0-221.3mo). Median OS was 61.5 months (51.4-81.6mo) for GM and 37.4 months (31.3-42mo) for NGM (hazard ratio [HR] = 1.7; 95% CI = 1.3-2.2, P<0.001). In univariate OS analysis, age, delay between initial diagnosis and metastases, MSKCC, bone/lung metastases, and GM or NGM group were significant parameters (P<0.001). In multivariate analysis, adjusted according to MSKCC risk group, NGM vs. GM was a strong prognostic factor (HR = 1.4; 95% CI = 1.0-1.8, P=0.026); bone or liver metastases were also significant (HR = 1.3; 95% CI = 1.1-1.7, P<0.02; HR = 1.4; 95% CI = 1.1-1.7, P<0.02, respectively). Even in patients without bone or liver metastases, GM status was significant (HR = 1.8; 95% CI = 1.2-2.7, P<0.004).
  
  
  CONCLUSIONS
  This large retrospective study shows that the presence of at least 1 GM site in development of mccRCC was associated with a significantly longer OS. The presence of GMs vs. NGM disease was an independent prognostic factor for survival irrespective of the presence or absence of bone or liver metastases. This finding could affect daily practice in which patients with mccRCC and GMs should receive more aggressive treatment with a potential for long-term survival. The causal mechanisms for this improved prognosis in GM mccRCC would be evaluated in translational studies.
authors.affiliation: Medical Oncology, Institut Paoli-Calmettes Marseille, Aix-Marseille Université, Marseille, France. Electronic address: gravisg@ipc.unicancer.fr.
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Gravis
authors.affiliation: Medical Oncology, Institut Paoli-Calmettes Marseille, Aix-Marseille Université, Marseille, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Chanez
authors.affiliation: Medical Oncology, Institut Gustave-Roussy, Villejuif, France.
authors.forename: Lisa
authors.initials: L
authors.lastname: Derosa
authors.affiliation: Medical Oncology, Leuven Cancer Institute, Leuven, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Beuselinck
authors.affiliation: Medical Oncology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Barthelemy
authors.affiliation: Medical Oncology, Centre Eugène Marquis, Rennes, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laguerre
authors.affiliation: Medical Oncology, Centre François Baclesse, Caen, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Brachet
authors.affiliation: Medical Oncology, Centre François Baclesse, Caen, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.affiliation: Medical Oncology, Institut Gustave-Roussy, Villejuif, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.affiliation: School of Medicine, University of St. Andrews, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Harrison
authors.affiliation: Edinburgh Urological Cancer Group, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Laird
authors.affiliation: Department of Medical Oncology, St James׳s Institute of Oncology, Leeds, UK.
authors.forename: Naveen
authors.initials: N
authors.lastname: Vasudev
authors.affiliation: Department of Medical Oncology, St James׳s Institute of Oncology, Leeds, UK.
authors.forename: Christy
authors.initials: C
authors.lastname: Ralph
authors.affiliation: The Royal Marsden Hospital, Fulham Road, London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.affiliation: The Royal Marsden Hospital, Fulham Road, London, UK.
authors.forename: Hazel
authors.initials: H
authors.lastname: Lote
authors.affiliation: Radiotherapy Department, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Naji
authors.initials: N
authors.lastname: Salem
authors.affiliation: Urological Department, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jochen
authors.initials: J
authors.lastname: Walz
authors.affiliation: Biopathology Department, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Thomassin
authors.affiliation: Department of Biostatistics, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sfumato
authors.affiliation: Edinburgh Urological Cancer Group, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: Grant D
authors.initials: GD
authors.lastname: Stewart
authors.affiliation: Department of Biostatistics, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Boher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors
keywords: Antiangiogenic therapy; Clear cell renal carcinoma; Glandular metastases; Kidney cancer; Prognosis factors; Survival outcome; Targeted therapies