title: Clinicopathological predictors of benefit from adjuvant chemotherapy for stage C colorectal cancer: Microsatellite unstable cases benefit.
abstract: OBJECTIVE
  In colorectal cancer (CRC), adjuvant therapy is offered on the basis of stage and attempts to identify factors to better target treatment have not been successful. Recent work suggested that mismatch repair deficient CRCs may not benefit from 5FU adjuvant chemotherapy but studies remain conflicting. We aimed to determine if gender, tumor site, tumor pathological characteristics and microsatellite instability (MSI) predict survival benefit from adjuvant chemotherapy in stage C CRC.
  
  
  METHODS
  Data were collated on ACPS (Australian Clinico-pathological Staging System) stage C CRC cases that underwent curative resection over a 23-year period. Pathology was reevaluated, DNA was extracted from the formalin-fixed paraffin specimen, and MSI status was established by BAT26 instability. Multivariate analysis was performed using Cox proportional hazard model and effects modification interaction testing.
  
  
  RESULTS
  In total 814 unselected cases were included, of whom 37% received chemotherapy. Seventy-seven cases exhibited MSI. Overall, adjuvant chemotherapy produced a cancer-specific survival benefit (HR 0.52, 95% CI 0.39-0.70; P < 0.0001). On interaction testing, none of the examined parameters significantly influenced the magnitude of that survival benefit. Chemotherapy was beneficial in both the MSI (HR 0.08, 95% CI 0.02-0.27; P = < 0.0001) and the microsatellite stable cohort (HR 0.62, 95% CI 0.47-0.81; P = 0.001).
  
  
  CONCLUSIONS
  These results suggest that survival benefit from 5FU adjuvant chemotherapy for stage C CRC does not vary according to gender, site of tumor, pathological characteristics or MSI status. This study suggests that it would be unwise to exclude patients from being offered adjuvant chemotherapy on the basis of MSI.
authors.affiliation: Royal Adelaide Hospital, Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia.|Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Thomas
authors.affiliation: The Queen Elizabeth Hospital, Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia.|Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hewett
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia.|Anatomical Pathology, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Ruszkiewicz
authors.affiliation: Royal Adelaide Hospital, Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia.|Department of Surgery, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: James W E
authors.initials: JW
authors.lastname: Moore
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001315:Australia; D014408:Biomarkers, Tumor / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor
keywords: adjuvant; chemotherapy; colorectal cancer; microsatellite instability; predictive biomarker