title: Patterns and management of distant failure in locally advanced rectal cancer: a cohort study.
abstract: OBJECTIVE
  To determine the long-term outcomes of locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (CRT) and surgery, and to analyze the management and survival once distant failure has developed.
  
  
  METHODS
  Data from LARC patients treated from 2000 to 2010 were retrospectively reviewed. CRT protocols were based on fluoropirimidines ± oxaliplatin. Follow-up consisted of physical examination, carcinoembryonic antigen levels, and chest-abdominal-pelvic CT scan.
  
  
  RESULTS
  The study included 228 patients with a mean age of 59 years. Forty-eight (21.1 %) patients had distant recurrence and 6 patients (2.6 %) had local recurrence. Median follow-up was 49 months. The 5- and 10-year actuarial disease free survival was 75.3 and 65.0 %, respectively. The 5- and 10-year actuarial overall survival (OS) was 89.6 and 71.2 %, respectively. Patients were classified as having liver (14 patients) or lung (27 patients) relapse according to the organ firstly metastasized. The variables significantly associated by univariate Cox analysis to survival were the achievement of an R0 metastases resection and the Köhne risk index, while the metastatic site showed a statistical trend. By multivariate Cox analysis, the only variable associated with survival was a R0 resection (HR = 16.3, p < 0.001). Median OS for patients undergoing a R0 resection was 73 months (95 % CI 67.8-78.2) compared to 25 months (95 % CI 5.47-44.5) in those non-operated patients (p < 0.001).
  
  
  CONCLUSIONS
  Combined treatment for LARC obtains a 5-year OS rounding 90 %. Follow-up based on thoracic-abdominal CT scan allows an early diagnosis of metastatic lesions. Surgical resection of metastases, regardless of their location, greatly increases the patient's survival rate.
authors.affiliation: Department of General Surgery, Complejo Asistencial Universitario de León, c/Altos de Nava s/n, 24008, León, Spain. jarredondo@outlook.es.
authors.forename: J
authors.identifier: http://orcid.org/0000-0001-8077-6092
authors.initials: J
authors.lastname: Arredondo
authors.affiliation: Department of General Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Baixauli
authors.affiliation: Department of Medical Oncology, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rodríguez
authors.affiliation: Department of Pathology, School of Medicine, Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Beorlegui
authors.affiliation: Department of Radiation Oncology, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Arbea
authors.affiliation: Department of General Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Zozaya
authors.affiliation: Department of Thoracic Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
authors.forename: W
authors.initials: W
authors.lastname: Torre
authors.affiliation: Department of General Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: -Cienfuegos
authors.affiliation: Department of General Surgery, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008, Pamplona, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Hernández-Lizoáin
mesh_terms: D000328:Adult; D000368:Aged; D059186:Chemoradiotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D012189:Retrospective Studies
keywords: Liver metastases; Locally advanced rectal cancer; Lung metastases; Metastasectomy; Neoadjuvant treatment