title: Disease-specific survival in de novo metastatic renal cell carcinoma in the cytokine and targeted therapy era.
abstract: BACKGROUND
  Recent phase III studies of targeted agents for metastatic renal cell carcinoma (mRCC) have generated median survival estimates that far exceed those observed during the cytokine era. However, substantial population-based data does not exist to confirm this trend. We sought to determine whether survival has improved for patients with mRCC diagnosed in the era of targeted therapies, as compared to the era of immunotherapy.
  
  
  METHODS
  The Surveillance, Epidemiology, and End Results (SEER) Registry was used to identify patients aged 18 and older diagnosed stage IV RCC between 1992 and 2009. Patients had documented clear cell, papillary or chromophobe histology. The Kaplan Meier method and log-rank test were used to compare disease-specific survival (DSS) for patients diagnosed from 1992-2004 (i.e., the cytokine era) and 2005-2009 (i.e., the targeted therapy era). Univariate and multivariate analyses of relevant clinicopathologic characteristics were also performed.
  
  
  RESULTS
  Of 5,176 patients identified using the above characteristics, 2,392 patients were diagnosed from 1992-2004 and 2,784 from 2005-2009. Median DSS was improved in those patients diagnosed from 2005-2009 (16 months vs 13 months; P<0.0001). A similar temporal trend towards improving survival was noted in patients with clear cell (P = 0.0006), but not in patients with non-clear cell disease (P = 0.32). Notable findings on multivariate analysis include an association between shorter DSS and the following characteristics: (1) diagnosis from 1992-2004, (2) advanced age (80+), and (3) absence of cytoreductive nephrectomy.
  
  
  CONCLUSIONS
  These data reflect progress in the management of mRCC, specifically in the era of targeted therapies. Notably, it was inferred that certain treatment strategies were employed during pre-specified time periods, representing a major caveat of the current analysis. Further studies related to the influence of age and race/ethnicity are warranted, as are studies exploring the role of cytoreductive nephrectomy and novel treatments for non-clear cell disease.
authors: Department of Medical Oncology & Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, California, United States of America. spal@coh.org
authors: Sumanta K
authors: SK
authors: Pal
authors: Rebecca A
authors: RA
authors: Nelson
authors: Nicholas
authors: N
authors: Vogelzang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D016207:Cytokines / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009392:Nephrectomy; D012042:Registries; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D016207:Cytokines
references: Clin Cancer Res. 2004 Sep 15;10(18 Pt 2):6302S-3S
references: 15448021
references: J Clin Oncol. 2010 Feb 20;28(6):1061-8
references: 20100962
references: Clin Cancer Res. 2011 Aug 15;17(16):5443-50
references: 21828239
references: Lancet Oncol. 2012 Sep;13(9):927-35
references: 22877847
references: J Clin Oncol. 1996 Aug;14(8):2410-1
references: 8708739
references: Int J Urol. 2007 Nov;14(11):1000-4; discussion 1004
references: 17956525
references: N Engl J Med. 2007 May 31;356(22):2271-81
references: 17538086
references: J Clin Oncol. 2002 Jan 1;20(1):289-96
references: 11773181
references: Clin Genitourin Cancer. 2012 Jun;10(2):93-8
references: 22382008
references: J Clin Oncol. 2010 May 1;28(13):2144-50
references: 20368553
references: J Clin Oncol. 2009 Dec 1;27(34):5794-9
references: 19826129
references: Urology. 2006 Aug;68(2):296-301
references: 16904440
references: J Urol. 2012 Dec;188(6):2095-100
references: 23083849
references: N Engl J Med. 2010 Aug 19;363(8):733-42
references: 20818875
references: N Engl J Med. 2001 Dec 6;345(23):1655-9
references: 11759643
references: Lancet. 2008 Aug 9;372(9637):449-56
references: 18653228
references: Lancet. 2011 Dec 3;378(9807):1931-9
references: 22056247
references: N Engl J Med. 2007 Jan 11;356(2):125-34
references: 17215530
references: J Urol. 2008 May;179(5):1704-8
references: 18343443
references: J Clin Oncol. 2009 Aug 1;27(22):3584-90
references: 19487381