Outcomes among black patients with stage II and III colon cancer receiving chemotherapy: an analysis of ACCENT adjuvant trials

Abstract

Background: Among patients with resected colon cancer, black patients have worse survival than whites. We investigated whether disparities in survival and related endpoints would persist when patients were treated with identical therapies in controlled clinical trials.

Methods: We assessed 14,611 patients (1218 black and 13,393 white) who received standardized adjuvant treatment in 12 randomized controlled clinical trials conducted in North America for resected stage II and stage III colon cancer between 1977 and 2002. Individual patient data on covariates and outcomes were extracted from the Adjuvant Colon Cancer ENdpoinTs (ACCENT) database. The endpoints examined in this meta-analysis were overall survival (time to death), recurrence-free survival (time to recurrence or death), and recurrence-free interval (time to recurrence). Cox models were stratified by study and controlled for sex, stage, age, and treatment to determine the effect of race. Kaplan-Meier estimates were adjusted for similar covariates to control for confounding. All statistical tests were two-sided.

Results: Black patients were younger than whites (median age, 58 vs 61 years, respectively; P < .001) and more likely to be female (55% vs 45%, respectively; P < .001). Overall survival was worse in black patients than whites (hazard ratio [HR] of death = 1.22, 95% confidence interval [CI] = 1.11 to 1.34, P < .001). Five-year overall survival rates for blacks and whites were 68.2% and 72.8%, respectively. When subsets defined by sex, stage, and age were analyzed, overall survival was consistently worse in black patients. Recurrence-free survival was worse in black patients than whites (HR of recurrence or death = 1.14, 95% CI = 1.04 to 1.24, P = .0045). Three-year recurrence-free survival rates in blacks and whites were 68.4% and 72.1%, respectively. In contrast, recurrence-free interval was similar in black and white patients (HR of recurrence = 1.08, 95% CI = 0.97 to 1.19, P = .15). Three-year recurrence-free interval rates in blacks and whites were 71.3% and 74.2%, respectively.

Conclusions: Black patients with resected stage II and stage III colon cancer who were treated with the same therapy as white patients experienced worse overall and recurrence-free survival, but similar recurrence-free interval, compared with white patients. The differences in survival may be mostly because of factors unrelated to the patients' adjuvant colon cancer treatment.

Trial registration: ClinicalTrials.gov NCT00002593 NCT00003835 NCT00004931 NCT00096278 NCT00425152.

Figure 1

Forest plots of hazard ratios (black divided by white) for death (overall survival [OS]), recurrence or death (recurrence-free survival [RFS]), and recurrence (recurrence-free interval [RFI]). The vertical lines indicate a hazard ratio of 1.0 (no difference between black and white race), values less than 1.0 favor black patients, and values greater than 1.0 favor white patients. Solid rectangles represent the hazard ratio of each single randomized controlled trial; the area of each rectangle is proportional to the inverse of the variance of the estimate. The horizontal line represents the 95% confidence interval and arrowheads indicate that the confidence interval extends beyond the scale of the plot. The solid diamonds represent the overall estimated hazard ratio based on multivariable Cox models of overall survival, recurrence-free survival, and recurrence-free interval controlling for sex, stage, age, and treatment, either not controlling for study (pooled) or stratifying by study (stratified); the diamond’s width represents the 95% confidence interval of the hazard ratio. A) OS. B) RFS. C) RFI. CALGB = Cancer And Leukemia Group B; CI = confidence interval; INT = Intergroup; NCCTG = North Central Cancer Treatment Group; NSABP = National Surgical Adjuvant Breast and Bowel Project.

Figure 2

Kaplan–Meier estimates adjusted by the method of Xie and Liu (21) for study, sex, stage, age, and type of treatment. A) Overall survival. B) Recurrence-free survival. C) Recurrence-free interval. Life tables for the number of patients at risk are presented below each graph. In a matrix within each graph, the number of patients and events are provided by race along with the hazard ratio and P value from a multivariable Cox model stratified by study and controlling for sex, stage, age, and treatment. The P values come from the two-sided Wald test.