title: Benefit of adjuvant immunotherapy in renal cell carcinoma: A myth or a reality?
abstract: BACKGROUND
  The benefit of adjuvant immunotherapy after nephrectomy in renal cell carcinoma (RCC) is controversial. The present study aimed to examine the possible benefit of adjuvant immunotherapy in various clinical settings.
  
  
  METHODS
  We retrospectively reviewed 436 patients with pT1-3N0-2M0 RCC who underwent radical or partial nephrectomy with curative intent at our institution between 1981 and 2009. Of them, 98 (22.5%) patients received adjuvant interferon-α (IFN-α) after surgery (adjuvant IFN-α group), while 338 (77.5%) did not (control group). The primary endpoint was cancer-specific survival (CSS). Univariate and multivariate analyses were conducted using log-rank tests and Cox proportional hazards models, respectively.
  
  
  RESULTS
  Fifty-two (11.9%) patients died from RCC with a median follow-up period of 96 months. Preliminary univariate analyses comparing CSS among treatment groups in each TNM setting revealed that CSS in the control group was equal or superior to that in the adjuvant IFN-α group in earlier stages, while the opposite trend was observed in more advanced stages. We evaluated the TNM cutoffs and demonstrated maximized benefit of adjuvant IFN-α in patients with pT2b-3cN0 (P = 0.0240). In multivariate analysis, ≥pT3 and pN1-2 were independent predictors for poor CSS in all patients. In the subgroups with ≥pT2 disease (n = 123), pN1-2 and no adjuvant treatment were significant poor prognostic factors.
  
  
  CONCLUSIONS
  Adjuvant immunotherapy after nephrectomy may be beneficial in pT2b-3cN0 RCC. Careful consideration is, however, required for interpretation of this observational study because of its selection bias and adverse effects of IFN-α.
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Taguchi
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Buti
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Melissa
authors.initials: M
authors.lastname: Bersanelli
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Igawa
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000601:surgery / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016898:Interferon-alpha / Q000627:therapeutic use; D007564:Japan; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000601:surgery / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009392:Nephrectomy; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D016898:Interferon-alpha