title: Extent of lymphadenectomy does not improve the survival of patients with renal cell carcinoma and nodal metastases: biases associated with the handling of missing data.
abstract: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: A recent population-based analysis suggested a potential survival benefit with respect to performing lymph node dissection at nephrectomy in node-positive patients with RCC. The findings of the present study failed to corroborate the association of a survival benefit with the performance of lymph node dissection at nephrectomy.
  
  
  OBJECTIVE
  Previous studies showed no survival benefit with respect to performing lymph node dissection (LND) at nephrectomy, whereas a recent population-based analysis suggested otherwise, although the latter relied on imputation. To reconcile the findings of that study by critically evaluating the handling of missing data.
  
  
  METHODS
  Study participants comprised patients diagnosed with non-metastatic renal cell carcinoma (RCC) of all stages who underwent LND at nephrectomy (n = 10 596). Multivariable Cox regression models were performed to predict cancer-specific mortality (CSM), where the primary variable of interest was the extent of LND. To examine differences in approaches with respect to handling missing data, separate analyses were performed: (i) imputed population; (ii) exclusion of patients with missing data; and (iii) inclusion of patients with missing data as a sub-category.
  
  
  RESULTS
  Overall, 2916 (28%) patients had missing tumour grade. In multivariable analyses, our findings showed that increasing the extent of LND was associated with a significant protective effect on CSM in patients with pN1 after imputation (hazard ratio [HR], 0.82; P = 0.04). By contrast, the extent of LND was no longer significantly associated with a lower risk of CSM after excluding patients with a missing tumour grade (HR, 0.83; P = 0.1) or when including patients with missing tumour grade as a sub-category (HR, 0.82; P = 0.05).
  
  
  CONCLUSIONS
  The findings of the present study failed to corroborate the association of a survival benefit with increasing extent of LND at nephrectomy. The different methodologies employed to account for missing data may introduce important biases. Such considerations are non-negligible with respect to the interpretation of results for investigators who rely on administrative cohorts.
authors.affiliation: Cancer Prognostics and Health Outcomes Unit.
authors.forename: Maxine
authors.initials: M
authors.lastname: Sun
authors.forename: Quoc-Dien
authors.initials: QD
authors.lastname: Trinh
authors.forename: Marco
authors.initials: M
authors.lastname: Bianchi
authors.forename: Jens
authors.initials: J
authors.lastname: Hansen
authors.forename: Firas
authors.initials: F
authors.lastname: Abdollah
authors.forename: Zhe
authors.initials: Z
authors.lastname: Tian
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Paul
authors.initials: P
authors.lastname: Perrotte
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
mesh_terms: D000368:Aged; D015982:Bias; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000556:secondary / Q000601:surgery*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D008197:Lymph Node Excision / Q000379:methods*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000379:methods*; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
keywords: extent; lymph node dissection; nephrectomy; renal cell carcinoma; survival