title: EMVI-positive stage II rectal cancer has similar clinical outcomes as stage III disease following pre-operative chemoradiotherapy.
abstract: BACKGROUND
  Stage II rectal cancers comprise a heterogeneous group, and there is significant variability in practise with regards to adjuvant chemotherapy; the survival benefit of chemotherapy is perceived to be <4% in these patients. However, in recent years, the emergence of additional prognostic factors such as extramural venous invasion (EMVI) suggests that there may be sub-stratification of stage II tumours and, further, we may be under-estimating the benefit adjuvant chemotherapy provides in high-risk patients. This study examined the outcomes of patients with stage II and III rectal cancer to determine whether EMVI status influences disease-free survival (DFS).
  
  
  METHODS
  An analysis of a prospectively maintained database was conducted of patients presenting with rectal cancer between 2006 and 2012. All patients underwent curative surgery and had no evidence of metastases at presentation. Clinicopathological factors were compared between stage II and III disease. The primary end point was 3-year DFS; univariate and multivariate analysis was carried out using Cox proportional hazards regression models; hazard ratios (HR) with 95% confidence intervals (CIs) were calculated.
  
  
  RESULTS
  Four hundred and seventy-eight patients were included: 233 stage II; 245 stage III. The prevalence of EMVI was 34.9%; 57 stage II patients (24.5%) and 110 stage III patients (44.9%). On multivariate analysis, only EMVI status was a significant factor for DFS. The adjusted HR for EMVI either alone or in combination with nodal involvement was 2.08 (95% CI 1.10-2.95) and 2.74 (95% CI 1.66-4.52), respectively.
  
  
  CONCLUSIONS
  EMVI is an independently poor prognostic factor for DFS for both stage II and stage III rectal cancer. These results demonstrate that there is risk-stratification within stage II tumours which affects prognosis. When discussing the use of adjuvant chemotherapy with patients that have EMVI-positive stage II tumours, these results provide evidence for a similarly increased risk of distant failure as stage III disease without venous invasion.
authors.affiliation: Department of GI Cancer, Royal Marsden Hospital, Fulham Road, London; Department of Surgery, Croydon University Hospital, London Road, Croydon; Department of Cancer and Surgery, Imperial College, London, UK. Electronic address: mans001@aol.com.
authors.forename: M
authors.initials: M
authors.lastname: Chand
authors.affiliation: Department of GI Cancer, Royal Marsden Hospital, Fulham Road, London; Department of Surgery, Croydon University Hospital, London Road, Croydon; Department of Cancer and Surgery, Imperial College, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Bhangu
authors.affiliation: Department of GI Cancer, Royal Marsden Hospital, Fulham Road, London; Department of Cancer and Surgery, Imperial College, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Wotherspoon
authors.affiliation: Department of GI Cancer, Royal Marsden Hospital, Fulham Road, London; Department of Cancer and Surgery, Imperial College, London, UK.
authors.forename: G W H
authors.initials: GWH
authors.lastname: Stamp
authors.affiliation: Department of Surgery, Croydon University Hospital, London Road, Croydon.
authors.forename: R I
authors.initials: RI
authors.lastname: Swift
authors.affiliation: Department of GI Cancer, Royal Marsden Hospital, Fulham Road, London.
authors.forename: I
authors.initials: I
authors.lastname: Chau
authors.affiliation: Department of GI Cancer, Royal Marsden Hospital, Fulham Road, London; Department of Cancer and Surgery, Imperial College, London, UK.
authors.forename: P P
authors.initials: PP
authors.lastname: Tekkis
authors.affiliation: Department of GI Cancer, Royal Marsden Hospital, Fulham Road, London.
authors.forename: G
authors.initials: G
authors.lastname: Brown
mesh_terms: D000368:Aged; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D057234:Preoperative Period; D011379:Prognosis; D016016:Proportional Hazards Models; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
keywords: EMVI; adjuvant chemotherapy; rectal cancer; stage II; venous invasion