title: Multivariate analysis of the relationship between male sex, disease-specific survival, and features of tumor aggressiveness in thyroid cancer of follicular cell origin.
abstract: BACKGROUND
  Disparity between the sexes in incidence, disease aggressiveness, and prognosis has been observed in various cancers. Although some investigators have reported that male sex is associated with a worse prognosis in thyroid cancer of follicular cell origin, this finding has not been widely studied and is controversial. Thus, using a large population-based database, we sought to better characterize the role of sex in disease aggressiveness and outcome.
  
  
  METHODS
  Data of patients with non-medullary thyroid cancer from the Surveillance, Epidemiology, and End Results 17 Registries Database (1988-2007) were used to compare the extent of disease and to analyze the effect of age, sex, race/ethnicity, presence of extrathyroidal extension, lymph node and distant metastases, disease stage, surgical treatment, radiotherapy, tumor size, and histological subtypes on disease-specific survival (DSS) by univariate and multivariate analyses.
  
  
  RESULTS
  We identified 61,523 patients with thyroid cancer (female:male=3.5:1). The median follow-up was 54 months. At diagnosis, 61.2% of men were ≥45 years, compared with 49.7% of women (p<0.01). Men had significantly more aggressive histological subtypes of differentiated thyroid cancer and undifferentiated thyroid cancer, regardless of age group (p<0.01). Moreover, men had significantly more advanced disease at presentation: larger primary tumor size (p<0.01), higher rates of extrathyroidal extension (p<0.01), regional lymph node metastasis (p<0.01), and distant metastasis (p<0.01). DSS stratified by pathology was significantly worse in men (227.5 and 234.3 months in men and women, respectively, p<0.01), despite more total thyroidectomies being performed in men (p<0.01). On multivariate analysis, independent prognostic factors for DSS included age ≥45 years, aggressive histopathology, advanced tumor staging, tumor >4 cm, extrathyroidal extension, lymph node and distant metastasis, less than subtotal thyroidectomy, and post-operative radiation. Sex was not an independent prognostic factor for DSS.
  
  
  CONCLUSIONS
  Men with thyroid cancer are more likely to present with more advanced disease, aggressive histological subtypes, and older age. However, sex is not an independent prognostic factor for DSS. Thus, men may benefit from more aggressive screening to detect thyroid cancer at an earlier stage.
authors.affiliation: Endocrine Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. niluboln@mail.nih.gov
authors.forename: Naris
authors.initials: N
authors.lastname: Nilubol
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhang
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis / Q000473:pathology* / Q000556:secondary / Q000628:therapy; D000328:Adult; D000367:Age Factors; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D018426:SEER Program; D012727:Sex Characteristics; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy; D013965:Thyroidectomy; D047368:Tumor Burden; D014481:United States