The predictive and prognostic value of sex in early-stage colon cancer: a pooled analysis of 33,345 patients from the ACCENT database

Clin Colorectal Cancer. 2013 Sep;12(3):179-87. doi: 10.1016/j.clcc.2013.04.004. Epub 2013 Jun 27.

Abstract

Purpose: To compare long-term outcomes between men and women in a large cohort of clinical trial participants with early-stage colon cancer, specifically by examining whether the prognostic effect of sex varies based on age, stage of disease, and type of adjuvant therapy received.

Methods: A pooled analysis of individual patient data from 33,345 patients with colon cancer enrolled in 24 phase III studies of various adjuvant systemic therapies was conducted. Chemotherapy consisted of (1) fluorouracil (5-FU), (2) 5-FU variations, (3) 5-FU plus oxaliplatin, (4) 5-FU plus irinotecan, or (5) oral fluoropyrimidine-based regimens. The primary endpoint was disease-free survival; secondary endpoints included overall survival and time to recurrence. Stratified Cox models were used to assess the effect of sex on outcomes. Multivariate models were used to assess adjusted effects and to explore the interaction among sex and other factors.

Results: A total of 18,244 (55%) men and 15,101 (45%) women were included. In the entire cohort, the median age was 61 years; 91% (24,868) were white; 31% (10,347) and 69% (22,964) had stage I/II and III disease, respectively. Overall, men had inferior prognoses when compared with women for time to recurrence (hazard ratio [HR] 1.05 [95% CI, 1.01-1.09]) and other endpoints after adjusting for age, stage, and treatment. Sex was not a predictive factor of treatment efficacy (P for interaction between sex and treatment when adjusting for age and stage were .40, .67, and .77 for disease-free survival, overall survival, and time to recurrence, respectively). In exploratory analyses, worse outcomes in men were more prominent in the older patients when adjusting for stage and treatment (HR 1.08 in age ≤ 65 years vs. HR 1.18 in age > 65 years; interaction P = .016 for disease-free survival). The stage of disease and type of adjuvant regimen did not modify the prognostic value of sex.

Conclusions: Sex is a modest independent prognostic marker for patients with early-stage colon cancer, particularly in older patients.

Keywords: Colon cancer; Outcomes; Sex; Survival.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / mortality*
  • Colonic Neoplasms / pathology
  • Female
  • Fluorouracil / administration & dosage
  • Follow-Up Studies
  • Humans
  • Irinotecan
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Prognosis
  • Sex Factors
  • Survival Rate
  • Young Adult

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • Irinotecan
  • Leucovorin
  • Fluorouracil
  • Camptothecin