title: Sex is an independent prognostic indicator for survival and relapse/progression-free survival in metastasized stage III to IV melanoma: a pooled analysis of five European organisation for research and treatment of cancer randomized controlled trials.
abstract: OBJECTIVE
  To study sex differences in survival and progression in patients with stage III or IV metastatic melanoma and to compare our results with published literature.
  
  
  METHODS
  Data were retrieved from three large, randomized, controlled trials of the European Organisation for Research and Treatment of Cancer in patients with stage III and two trials in patients with stage IV melanoma. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for females compared with males, adjusted for different sets of confounders for stage III and stage IV, respectively.
  
  
  RESULTS
  In 2,734 stage III patients, females had a superior 5-year disease-specific survival (DSS) rate compared with males (51.5% v 43.3%), an adjusted HR for DSS of 0.85 (95% CI, 0.76 to 0.95), and an adjusted HR for relapse-free survival of 0.86 (95% CI, 0.77 to 0.95). In 1,306 stage IV patients, females also exhibited an advantage in DSS (2-year survival rate, 14.1% v 19.0%; adjusted HR, 0.81; 95% CI, 0.72 to 0.92) as well as for progression-free survival (adjusted HR, 0.79; 95% CI, 0.70 to 0.88). This female advantage was consistent across pre- and postmenopausal age categories and across different prognostic subgroups. However, the female advantage seems to become smaller in patients with higher metastatic tumor load.
  
  
  CONCLUSIONS
  The persistent independent female advantage, even after metastasis to lymph nodes and distant sites, contradicts theories about sex behavioral differences as an explanation for this phenomenon. A biologic sex trait seems to profoundly influence melanoma progression and survival, even in advanced disease.
authors.affiliation: Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Arjen
authors.initials: A
authors.lastname: Joosse
authors.forename: Sandra
authors.initials: S
authors.lastname: Collette
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Tamar
authors.initials: T
authors.lastname: Nijsten
authors.forename: Poulam M
authors.initials: PM
authors.lastname: Patel
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keilholz
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Jan Willem W
authors.initials: JW
authors.lastname: Coebergh
authors.forename: Esther
authors.initials: E
authors.lastname: de Vries
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data*; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012737:Sex Factors; D015996:Survival Rate; D013997:Time Factors