title: Paraneoplastic syndromes are associated with adverse prognosis among patients with renal cell carcinoma undergoing nephrectomy.
abstract: OBJECTIVE
  To analyze the association of paraneoplastic syndromes (PNS) with progression-free (PFS) and cancer-specific survival (CSS) among patients with renal cell carcinoma (RCC) undergoing nephrectomy.
  
  
  METHODS
  We performed a retrospective analysis of 2865 patients undergoing nephrectomy for localized RCC at Mayo Clinic from 1990 to 2010. PNS analyzed were anemia, polycythemia, hypercalcemia, recent-onset hypertension, and liver dysfunction. PFS and CSS were estimated using Kaplan-Meier method and compared with Cox proportional hazard models, unadjusted and adjusted for clinicopathologic features.
  
  
  RESULTS
  A total of 661 (23 %) patients had anemia, 37 (1 %) had polycythemia, 177 (9 %) had hypercalcemia, 51 (2 %) had recent-onset hypertension, and 224 (10 %) had liver dysfunction at time of nephrectomy. Patients with PNS were more likely to have high-grade tumors and advanced disease stages. A total of 675 (24 %) patients developed progression and 1171 (41 %) died of RCC, over a median follow-up of 8.2 years. On univariable analysis, the presence of any PNS was associated with inferior CSS [hazard ratio (HR) = 1.86, p = 0.007] and a trend toward shorter PFS (HR = 1.33, p = 0.07) compared with patients without PNS. Specifically, anemia, polycythemia, hypercalcemia, and liver dysfunction were each associated with inferior CSS and PFS (all p < 0.05). However, on multivariable analysis PNS (overall or each individual syndrome) did not remain independently associated with CSS or PFS.
  
  
  CONCLUSIONS
  Patients with RCC undergoing nephrectomy presenting with PNS have worse oncologic outcome than those with incidentally found tumors. However, the adverse outcome among PNS patients seems to be largely explained by adverse pathologic features of these tumors.
authors.affiliation: Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. moreira.daniel@mayo.edu.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Moreira
authors.affiliation: Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Gershman
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Foundation for Medical Education and Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lohse
authors.affiliation: Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boorjian
authors.affiliation: Department of Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.affiliation: Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Leibovich
authors.affiliation: Department of Urology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
authors.forename: Robert Houston
authors.initials: RH
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009392:Nephrectomy; D010257:Paraneoplastic Syndromes / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology; D055815:Young Adult
keywords: Cohort studies; Disease-free survival; Kidney cancer; Nephrectomy; Paraneoplastic syndromes