title: Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases.
abstract: OBJECTIVE
  To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma.
  
  
  METHODS
  Complete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American Joint Committee on Cancer (AJCC) melanoma staging database. Kaplan-Meier and Cox multivariate survival analyses were performed.
  
  
  RESULTS
  Among all 2,313 patients with stage III disease, 81% had micrometastases, and 19% had clinically detectable macrometastases. The 5-year overall survival was 63%; it was 67% for patients with nodal micrometastases, and it was 43% for those with nodal macrometastases (P < .001). Tremendous heterogeneity in survival was observed, particularly in the microscopically detected nodal metastasis subset (from 23% to 87% for 5-year survival). Multivariate analysis demonstrated that in patients with nodal micrometastases, number of tumor-containing lymph nodes, primary tumor thickness, patient age, ulceration, and anatomic site of the primary independently predicted survival (all P < .01). When added to the model, primary tumor mitotic rate was the second-most powerful predictor of survival after the number of tumor-containing nodes. In contrast, for patients with nodal macrometastases, the number of tumor-containing nodes, primary ulceration, and patient age independently predicted survival (P < .01).
  
  
  CONCLUSIONS
  In this multi-institutional analysis, we demonstrated remarkable heterogeneity of prognosis among patients with stage III melanoma, especially among those with nodal micrometastases. These results should be incorporated into the design and interpretation of future clinical trials involving patients with stage III melanoma.
authors.affiliation: Department of Surgery, Johns Hopkins Medical Institutions, 600 N Wolfe St, Osler 624, Baltimore, MD 21287, USA. balchch@jhmi.edu
authors.forename: Charles M
authors.initials: CM
authors.lastname: Balch
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.forename: Seng-Jaw
authors.initials: SJ
authors.lastname: Soong
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.forename: Shouluan
authors.initials: S
authors.lastname: Ding
authors.forename: David R
authors.initials: DR
authors.lastname: Byrd
authors.forename: Natale
authors.initials: N
authors.lastname: Cascinelli
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Cochran
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Coit
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Timothy
authors.initials: T
authors.lastname: Johnson
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: Stanley P
authors.initials: SP
authors.lastname: Leong
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.forename: Donald L
authors.initials: DL
authors.lastname: Morton
authors.forename: Merrick I
authors.initials: MI
authors.lastname: Ross
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D016009:Chi-Square Distribution; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000556:secondary*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000401:mortality* / Q000473:pathology*; D013997:Time Factors; D014481:United States / Q000453:epidemiology