title: Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis.
abstract: OBJECTIVE
  Metastatic renal cancer is associated with a poor prognosis. Recent advances in immunotherapy for this problem have rekindled interest in cytoreductive nephrectomy. We report a combined analysis of 2 prospective randomized trials that used an identical study protocol.
  
  
  METHODS
  A total of 331 patients were randomized to 2 identical protocols comparing cytoreductive nephrectomy plus interferon alpha-2b vs interferon alpha-2b alone in patients with metastatic renal cancer, in whom the primary tumor was present and believed to be resectable. The primary end point for each trial was overall survival with a secondary end point of the response rate. Patients were stratified at pre-randomization by performance status (0 or 1), site of metastases (lung only vs other) and disease measurability. All results were analyzed by intent to treat criteria. Assuming a median survival of 1 year for interferon only, the Southwest Oncology Group trial was designed to detect a 50% improvement in median survival duration and a 15% improvement in response rate with a power of 0.85. The European Organization for the Research and Treatment of Cancer accrued an additional 80 patients in that study.
  
  
  RESULTS
  The combined analysis of these 2 trials yielded a median survival of 13.6 months for nephrectomy plus interferon vs 7.8 months for interferon alone. This difference represents a 31% decrease in the risk of death (p = 0.002). There was no evidence of a difference in the size of the treatment effect according to pre-randomization stratification factors.
  
  
  CONCLUSIONS
  Cytoreductive nephrectomy appears to improve significantly overall survival in patients with metastatic renal cancer treated with interferon immunotherapy independent of patient performance status, the site of metastases and the presence of measurable disease. Although it is highly statistically significant, the overall survival advantage is only 5.8 months for the entire group. These data emphasize the need to determine if this survival advantage can be further improved using more aggressive immunotherapy or other novel agents in the setting of cytoreductive nephrectomy.
authors.affiliation: Southwest Oncology Group and European Organization for the Research and Treatment of Cancer Genitourinary Group, Loyola University Medical Center, Maywood, Illinois, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Flanigan
authors.forename: G
authors.initials: G
authors.lastname: Mickisch
authors.forename: Richard
authors.initials: R
authors.lastname: Sylvester
authors.forename: Cathy
authors.initials: C
authors.lastname: Tangen
authors.forename: H
authors.initials: H
authors.lastname: Van Poppel
authors.forename: E David
authors.initials: ED
authors.lastname: Crawford
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009392:Nephrectomy / Q000379:methods*; D011446:Prospective Studies; D011994:Recombinant Proteins
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins