title: The Impact of Mismatch Repair Status in Colorectal Cancer on the Decision to Treat With Adjuvant Chemotherapy: An Australian Population-Based Multicenter Study.
abstract: Testing for mismatch repair (MMR) status in colorectal cancer (CRC) may provide useful prognostic and predictive information. We evaluated the impact of such testing on real-world practice regarding adjuvant chemotherapy for patients with resected CRC.
  
  
  
  A total of 175 patients with stage II and III mismatch repair-deficient (MMRD) CRC were identified from an Australian population-based study of incident CRCs. Their treatment decisions were compared with those for a cohort of 773 stage-matched patients with mismatch repair-proficient (MMRP) CRCs. The effect of MMR status, age, and pathologic characteristics on treatment decisions was determined using multiple regression analysis.
  
  
  
  Overall, 32% of patients in stage II and 71% of patients in stage III received adjuvant chemotherapy. Among the stage II patients, those with MMRD cancer were less likely to receive chemotherapy than were MMRP cases (15% vs. 38%; p < .0001). In this group, the treatment decision was influenced by age, tumor location, and T stage. MMR status influenced the treatment decision such that its impact diminished with increasing patient age. Among patients with stage III tumors, no difference was found in the chemotherapy rates between the MMRD and MMRP cases. In this group, age was the only significant predictor of the treatment decision.
  
  
  
  The findings of this study suggest that knowledge of the MMR status of sporadic CRC influences treatment decisions for stage II patients, in an era when clear recommendations as to how these findings should influence practice are lacking.
  
  
  
  Microsatellite instability (MSI) is a molecular marker of defective DNA mismatch repair found in 15% of sporadic colorectal cancers. Until recently, expert guidelines on the role of MSI as a valid biomarker in the selection of stage II patients for adjuvant chemotherapy were lacking. Conducted at a time when the clinical utility of routine MSI testing was unclear, this study found that clinicians were influenced by MSI status in selecting stage II patients for chemotherapy. Furthermore, the impact of MSI on treatment decisions was greatest in younger patients and declined progressively until age 80 years, when no effect was found.
authors.affiliation: Prince of Wales Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: He
authors.affiliation: University of Queensland, St. Lucia, Queensland, Australia.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Hawkins
authors.affiliation: Prince of Wales Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mak
authors.affiliation: NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia.
authors.forename: Felicia
authors.initials: F
authors.lastname: Roncolato
authors.affiliation: Prince of Wales Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: St. George Hospital, Kogarah, New South Wales, Australia.
authors.forename: Winston
authors.initials: W
authors.lastname: Liauw
authors.affiliation: Wollongong Hospital, Wollongong, New South Wales, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Clingan
authors.affiliation: Prince of Wales Clinical School, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Melvin
authors.initials: M
authors.lastname: Chin
authors.affiliation: Prince of Wales Clinical School, UNSW Australia, Sydney, New South Wales, Australia University of Queensland, St. Lucia, Queensland, Australia r.ward@uq.edu.au.
authors.forename: Robyn L
authors.initials: RL
authors.lastname: Ward
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053843:DNA Mismatch Repair; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D012044:Regression Analysis
chemical_list: D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil
keywords: Adjuvant chemotherapy; Colorectal cancer; Microsatellite instability; Mismatch repair deficiency; Treatment decisions