title: Occult metastases in lymph nodes predict survival in resectable non-small-cell lung cancer: report of the ACOSOG Z0040 trial.
abstract: OBJECTIVE
  The survival of patients with non-small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival.
  
  
  METHODS
  Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant.
  
  
  RESULTS
  From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009).
  
  
  CONCLUSIONS
  In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.
authors: Thoracic Surgery Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. ruschv@mskcc.org
authors: Valerie W
authors: VW
authors: Rusch
authors: Debra
authors: D
authors: Hawes
authors: Paul A
authors: PA
authors: Decker
authors: Sue Ellen
authors: SE
authors: Martin
authors: Andrea
authors: A
authors: Abati
authors: Rodney J
authors: RJ
authors: Landreneau
authors: G Alexander
authors: GA
authors: Patterson
authors: Richard I
authors: RI
authors: Inculet
authors: David R
authors: DR
authors: Jones
authors: Richard A
authors: RA
authors: Malthaner
authors: Robbin G
authors: RG
authors: Cohen
authors: Karla
authors: K
authors: Ballman
authors: Joe B
authors: JB
authors: Putnam
authors: Richard J
authors: RJ
authors: Cote
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models