title: Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer.
abstract: OBJECTIVE
  Our aims were to (1) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy (CMT) followed by total mesorectal excision (TME), (2) identify factors predictive of oncologic outcome, and (3) determine the oncologic significance of the extent of pathologic tumor response.
  
  
  BACKGROUND
  Locally advanced (T3-4 and/or N1) rectal adenocarcinoma is commonly treated with preoperative CMT and TME. However, the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown.
  
  
  METHODS
  Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6 cm from the anal verge (range 0-15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5-fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A prospectively collected database was queried for long-term oncologic outcome and predictive clinicopathologic factors.
  
  
  RESULTS
  With a median follow-up of 44 months, the estimated 10-year overall survival (OS) was 58% and 10 year recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic response >95%, lymphovascular invasion and/or perineural invasion (PNI), and positive lymph nodes were significantly associated with OS and RFS. Patients with a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P = 0.002).
  
  
  CONCLUSIONS
  Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study.
authors.affiliation: Department of Surgery-Colorectal Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. guillenmj@mskcc.org
authors.forename: Jose G
authors.initials: JG
authors.lastname: Guillem
authors.forename: David B
authors.initials: DB
authors.lastname: Chessin
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Cohen
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: Warren
authors.initials: W
authors.lastname: Enker
authors.forename: Philip B
authors.initials: PB
authors.lastname: Paty
authors.forename: Martin R
authors.initials: MR
authors.lastname: Weiser
authors.forename: David
authors.initials: D
authors.lastname: Klimstra
authors.forename: Leonard
authors.initials: L
authors.lastname: Saltz
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Minsky
authors.forename: W Douglas
authors.initials: WD
authors.lastname: Wong
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery*; D016019:Survival Analysis; D016896:Treatment Outcome