title: The significance of intrapulmonary metastasis in non-small cell lung cancer: upstaging or downstaging? A re-appraisal for the next TNM staging system.
abstract: OBJECTIVE
  The management of patients with non-small cell lung cancer (NSCLC) with intrapulmonary metastases (PM) is controversial. In TNM classification, PM are designed as T4 when in the same lobe of the primary tumour (PM1) and M1 when in a different lobe(s) (PM2). Some authors have questioned the negative prognostic impact of PM. The present study assessed prevalence, correlation with clinico-pathologic variables and impact on survival of PM, along with a review of the literature.
  
  
  METHODS
  From January 1993 to December 2006, 2013 NSCLC patients underwent surgical resection at our institution. Of these, 74 presented with PM (39 PM1, 35 PM2). Patients with bronchioloalveolar carcinoma (BAC), carcinoid tumours, contralateral disease and preoperative chemo/radiotherapy were excluded from the analysis. A logistic regression analysis was undertaken to evaluate a relationship between the presence of PM and different clinico-pathologic variables. Survival analysis was undertaken to investigate the prognostic significance of PM.
  
  
  RESULTS
  PM represent 3.6% of our patient population of operated NSCLC. Metastases were multiple in 36 cases and single in 38. Thirty-six patients had node-negative disease. Among all the variables for the logistic regression analysis only vascular invasion (OR: 0. 45; 95% CI 0.24-0.85, p=0.01) and N status (OR: 0. 6; 95% CI 0.43-0.82, p=0.001) were significantly correlated with the presence of PM. Median survival rates of PM1, PM2, other T4 and other M1 patients were 25, 23, 15 and 14 months, respectively. A survival advantage was observed in patients with PM as compared to other T4/M1 patients, although the difference was not significant either overall (p=0.21) or in the N0 disease group (p=0.12).
  
  
  CONCLUSIONS
  The presence of PM in NSCLC patients is a rare occurrence. Risk factors for the development of PM are a microscopic vascular invasion and a high nodal status. A survival advantage over other T4/M1 patients is evident from our experience, although not significant. The results of the literature which have been accumulating in the most recent years including ours bend to the conclusion that there is sufficient validated information to consider a downstaging in the presence of intrapulmonary metastases from NSCLC for the seventh edition of the TNM classification.
authors.affiliation: Department of Thoracic Surgery, University of Torino, Ospedale Molinette, Via Genova 3, Turin, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Oliaro
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Filosso
authors.forename: Antonio
authors.initials: A
authors.lastname: Cavallo
authors.forename: Roberto
authors.initials: R
authors.lastname: Giobbe
authors.forename: Claudio
authors.initials: C
authors.lastname: Mossetti
authors.forename: Paraskevas
authors.initials: P
authors.lastname: Lyberis
authors.forename: Riccardo Carlo
authors.initials: RC
authors.lastname: Cristofori
authors.forename: Enrico
authors.initials: E
authors.lastname: Ruffini
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011013:Pneumonectomy / Q000379:methods; D011379:Prognosis; D016019:Survival Analysis