title: Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis.
abstract: OBJECTIVE
  To determine survival and relapse rates by T and N stage and treatment method in five randomized phase III North American rectal adjuvant studies.
  
  
  METHODS
  Data were pooled from 3,791 eligible patients enrolled onto North Central Cancer Treatment Group (NCCTG) 79-47-51, NCCTG 86-47-51, US Gastrointestinal Intergroup 0114, National Surgical Adjuvant Breast and Bowel Project (NSABP) R01, and NSABP R02. Surgery alone (S) was the treatment arm in 179 patients. The remaining patients received adjuvant treatment as follows: irradiation (RT) alone (n = 281), RT + fluorouracil (FU) +/- semustine bolus chemotherapy (CT; n = 779), RT + protracted venous infusion CT (n = 325), RT + FU +/- leucovorin or levamisole bolus CT (n = 1,695), or CT alone (n = 532). Five-year follow-up was available in 94% of surviving patients, and 8-year follow-up, in 62%.
  
  
  RESULTS
  Overall (OS) and disease-free survival were dependent on TN stage, NT stage, and treatment method. Even among N2 patients, T substage influenced 5-year OS (T1-2, 67%; T3, 44%; T4, 37%; P <.001). Three risk groups of patients were defined: (1) intermediate (T1-2/N1, T3/N0), (2) moderately high (T1-2/N2, T3/N1, T4/N0), and (3) high (T3/N2, T4/N1, T4/N2). For intermediate-risk patients, those receiving S plus CT had 5-year OS rates of 85% (T1-2/N1) and 84% (T3/N0), which was similar to results with S plus RT plus CT (T1-2/N1, 78% to 83%; T3/N0, 74% to 80%). For moderately high-risk lesions, 5-year OS ranged from 43% to 70% with S plus CT, and 44% to 80% with S plus RT plus CT. For high-risk lesions, 5-year OS ranged from 25% to 45% with S plus CT, and 29% to 57% with S plus RT plus CT.
  
  
  CONCLUSIONS
  Different treatment strategies may be indicated for intermediate-risk versus moderately high- or high-risk patients based on differential survival rates and rates of relapse. Use of trimodality treatment for all patients with intermediate-risk lesions may be excessive, since S plus CT resulted in 5-year OS of approximately 85%; however, 5-year disease-free survival rates with S plus CT were 78% (T1-2/N1) and 69%(T3/N0), indicating room for improvement.
authors.affiliation: Radiation Oncology Department, Mayo Clinic Cancer Center, Scottsdale, AZ 85259, USA. gunderson.leonard@mayo.edu
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Gunderson
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: Joel E
authors.initials: JE
authors.lastname: Tepper
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: Mirsada
authors.initials: M
authors.lastname: Begovic
authors.forename: Cristine
authors.initials: C
authors.lastname: Allmer
authors.forename: Linda
authors.initials: L
authors.lastname: Colangelo
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smalley
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Haller
authors.forename: James A
authors.initials: JA
authors.lastname: Martenson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mayer
authors.forename: Tyvin A
authors.initials: TA
authors.lastname: Rich
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: John S
authors.initials: JS
authors.lastname: MacDonald
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Willett
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D016208:Databases, Factual; D003657:Decision Making; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology