title: Prognostic Impact of Node-Spreading Pattern in Surgically Treated Small-Cell Lung Cancer: A Multicentric Analysis.
abstract: Although surgery in selected small-cell lung cancer (SCLC) patients has been proposed as a part of multimodality therapy, so far, the prognostic impact of node-spreading pattern has not been fully elucidated. To investigate this issue, a retrospective analysis was performed.
  
  
  
  From 01/1996 to 12/2012, clinico-pathological, surgical, and oncological features were retrospectively reviewed in a multicentric cohort of 154 surgically treated SCLC patients. A multivariate Cox proportional hazard model was developed using stepwise regression, in order to identify independent outcome predictors. Overall (OS), cancer-specific (CSS), and Relapse-free survival (RFS) were calculated by Kaplan-Meier method.
  
  
  
  Overall, median OS, CSS, and RFS were 29 (95 % CI 18-39), 48 (95 % CI 19-78), and 22 (95 % CI 17-27) months, respectively. Lymphadenectomy was performed in 140 (90.9 %) patients (median number of harvested nodes: 11.5). Sixty-seven (47.9 %) pN0-cases experienced the best long-term survival (CSS: 71, RFS: 62 months; p < 0.0001). Among node-positive patients, no prognostic differences were found between pN1 and pN2 involvement (CSS: 22 vs. 15, and RFS: 14 vs. 10 months, respectively; p = 0.99). By splitting node-positive SCLC according to concurrent N1-invasion, N0N2-patients showed a worse CSS compared to those cases with combined N1N2-involvement (N0N2: 8 months vs. N1N2: 22 months; p = 0.04). On the other hand, the number of metastatic stations (p = 0.80) and the specific node-level (p = 0.85) did not affect CSS. At multivariate analysis, pN+ (HR: 3.05, 95 % CI 1.21-7.67, p = 0.02) and ratio between metastatic and resected lymph-nodes (RL, HR: 1.02, 95 % CI 1.00-1.04, p = 0.03) were independent predictors of CSS. Moreover, node-positive patients (HR: 3.60, 95 % CI 1.95-6.63, p < 0.0001) with tumor size ≥5 cm (HR: 1.85, 95 % CI 0.88-3.88, p = 0.10) experienced a worse RFS.
  
  
  
  In selected surgically treated SCLC, the long-term survival may be stratified according to the node-spreading pattern.
authors.affiliation: Thoracic Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Leuzzi
authors.affiliation: Unit of Thoracic Surgery, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy. filippo_lococo@yahoo.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Lococo
authors.affiliation: Thoracic Surgery Unit, Regina Elena National Cancer Institute - IFO, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Alessandrini
authors.affiliation: Scientific Direction, Regina Elena National Cancer Institute - IFO, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.affiliation: Thoracic Surgery Division, European Institute of Oncology, University of Milan, Milan, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Spaggiari
authors.affiliation: Department of Thoracic Surgery, University of Rome SAPIENZA, Policlinico Umberto I, Fondazione Eleonora Lorilard Spencer Cenci, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Venuta
authors.affiliation: Division of Thoracic Surgery, S. Andrea Hospital, University of Rome SAPIENZA, Fondazione Eleonora Lorilard Spencer Cenci, Rome, Italy.
authors.forename: Erino A
authors.initials: EA
authors.lastname: Rendina
authors.affiliation: Department of Thoracic Surgery, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Pierluigi M
authors.initials: PM
authors.lastname: Granone
authors.affiliation: Unit of Thoracic Surgery, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Rapicetta
authors.affiliation: Department of Thoracic Surgery, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Zannini
authors.affiliation: Thoracic Surgery Unit, V. Fazzi Hospital, Lecce, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Di Rienzo
authors.affiliation: Thoracic Surgery Unit, Cannizzaro Hospital, Catania, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Nicolosi
authors.affiliation: Thoracic Surgery Unit, Regina Elena National Cancer Institute - IFO, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Facciolo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary* / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000628:therapy*; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011013:Pneumonectomy; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D015996:Survival Rate; D047368:Tumor Burden
keywords: Lymphadenectomy; Multimodality therapy; Node-spreading pattern; Ratio; Small-cell lung cancer; Surgery