title: Nodal status, number of lymph nodes examined, and lymph node ratio: what defines prognosis after resection of colon adenocarcinoma?
abstract: BACKGROUND
  Lymph node ratio (LNR) has been proposed as an optimal staging variable for colorectal cancer. However, the interactive effect of total number of lymph nodes examined (TNLE) and the number of metastatic lymph nodes (NMLN) on survival has not been well characterized.
  
  
  METHODS
  Patients operated on for colon cancer between 1998 and 2007 were identified from the Surveillance, Epidemiology, and End Results database (n = 154,208) and randomly divided into development (75%) and validation (25%) datasets. The association of the TNLE and NMLN on survival was assessed using the Cox proportional hazards model with terms for interaction and nonlinearity with restricted cubic spline functions. Findings were confirmed in the validation dataset.
  
  
  RESULTS
  Both TNLE and NMLN were nonlinearly associated with survival. Patients with no lymph node metastasis had a decrease in the risk of death for each lymph node examined up to approximately 25 lymph nodes, while the effect of TNLE was negligible after approximately 10 negative lymph nodes (NNLN) in those with lymph node metastasis. The hazard ratio varied considerably according to the TNLE for a given LNR when LNR ≥ 0.5, ranging from 2.88 to 7.16 in those with an LNR = 1. The independent effects of NMLN and NNLN on survival were summarized in a model-based score, the N score. When patients in the validation set were categorized according to the N stage, the LNR, and the N score, only the N score was unaffected by differences in the TNLE.
  
  
  CONCLUSIONS
  The effect of the TNLE on survival does not have a unique, strong threshold (ie, 12 lymph nodes). The combined effect of NMLN and TNLE is complex and is not appropriately represented by the LNR. The N score may be an alternative to the N stage for prognostication of patients with colon cancer because it accounts for differences in nodal samples.
authors.affiliation: Department of Surgery, St Louis University School of Medicine, St Louis, MO.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Gleisner
authors.forename: Harveshp
authors.initials: H
authors.lastname: Mogal
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dodson
authors.forename: Jon
authors.initials: J
authors.lastname: Efron
authors.forename: Susan
authors.initials: S
authors.lastname: Gearhart
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Wick
authors.forename: Anne
authors.initials: A
authors.lastname: Lidor
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
mesh_terms: D000005:Abdomen; D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003082:Colectomy; D003110:Colonic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018426:SEER Program; D016896:Treatment Outcome
keywords: AIC; Akaike's information criteria; HR; LN; LNR; NMLN; NNLN; TNLE; hazard ratio; lymph node; lymph node ratio; number of metastatic lymph nodes; number of negative lymph nodes; total number of lymph nodes examined