title: The prognostic significance of nonsentinel lymph node metastasis in melanoma.
abstract: BACKGROUND
  We hypothesized that metastasis beyond the sentinel lymph nodes (SLN) to the nonsentinel nodes (NSN) is an important predictor of survival.
  
  
  METHODS
  Analysis was performed of a prospective multi-institutional study that included patients with melanoma ≥ 1.0 mm in Breslow thickness. All patients underwent SLN biopsy; completion lymphadenectomy was performed for all SLN metastases. Disease-free survival (DFS) and overall survival (OS) were computed by Kaplan-Meier analysis; univariate and multivariate analyses were performed to identify factors associated with differences in survival among groups.
  
  
  RESULTS
  A total of 2335 patients were analyzed over a median follow-up of 68 months. We compared 3 groups: SLN negative (n = 1988), SLN-only positive (n = 296), and both SLN and NSN positive (n = 51). The 5-year DFS rates were 85.5, 64.8, and 42.6% for groups 1, 2, and 3, respectively (P < 0.001). The 5-year OS rates were 85.5, 64.9, and 49.4%, respectively (P < 0.001). On univariate analysis, predictors of decreased OS included: SLN metastasis, NSN metastasis, increased total number of positive LN, increased ratio of positive LN to total LN, increased age, male gender, increased Breslow thickness, presence of ulceration, Clark level ≥ IV, and axial primary site (in all cases, P < 0.01). When the total number of positive LN and NSN status were evaluated using multivariate analysis, NSN status remained statistically significant (P < 0.01), while the total number of positive LN and LN ratio did not.
  
  
  CONCLUSIONS
  NSN melanoma metastasis is an independent prognostic factor for DFS and OS, which is distinct from the number of positive lymph nodes or the lymph node ratio.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of Louisville, James Graham Brown Cancer Center, Louisville, KY, USA.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Brown
authors.forename: Merrick I
authors.initials: MI
authors.lastname: Ross
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: R Dirk
authors.initials: RD
authors.lastname: Noyes
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Reintgen
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Hagendoorn
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Stromberg
authors.forename: Robert C G
authors.initials: RC
authors.lastname: Martin
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.forename: Charles R
authors.initials: CR
authors.lastname: Scoggins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000556:secondary* / Q000601:surgery; D015996:Survival Rate; D055815:Young Adult