The Predictive and Prognostic Value of Sex in Early-Stage Colon Cancer: A Pooled Analysis of 33,345 Patients from the ACCENT Database

Abstract

Our study compares the outcomes of men and women with early stage colon cancer by analyzing the ACCENT database. Overall, men experienced inferior prognoses when compared with women for time to recurrence after adjusting for age, stage, and treatment. Sex was not a predictive factor of treatment efficacy. In exploratory analyses, worse outcomes in men were more prominent in older patients, but the stage of disease and type of adjuvant regimen did not modify the prognostic value of sex. 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.

Gender differences in colorectal cancer survival: A meta‐analysis

“…31 However, sex is seldom identified as an independent prognostic factor in clinical trials involving patients with colorectal cancer as it is not usually examined as a possible source of interaction between the treatments and survival. 7,13,24,[32][33][34] Recent studies have showed that sex is a modest independent prognostic marker for patients with early-stage colon cancer, particularly in older patients, 19 and that conventional therapy for localized colorectal cancer produced a better survival outcome in females when compared with males, in randomized trials involving over 1000 patients. 7,13,24,[32][33][34] Recent studies have showed that sex is a modest independent prognostic marker for patients with early-stage colon cancer, particularly in older patients, 19 and that conventional therapy for localized colorectal cancer produced a better survival outcome in females when compared with males, in randomized trials involving over 1000 patients.…”

“…7,[12][13][14][15][16][17][18][19] Pooled analysis of OS showed a significant difference between women and men with slight heterogeneity in a fixed effects model(HR 5 0.87, 95% CI: 0.85-0.89, p < 0.00001; I 2 5 26%, p 5 0.22, Fig. Overall survival (OS) was significantly longer in female patients than male patients with colorectal cancer, as reported in the nine included studies.…”

“…12,17,19 Another three studies included HR of subgroup analysis according to stage, year and site. 12,17,19 Another three studies included HR of subgroup analysis according to stage, year and site.…”

“…Overall survival (OS) was significantly longer in female patients than male patients with colorectal cancer, as reported in the nine included studies. 7,[12][13][14][15][16][17][18][19] Pooled analysis of OS showed a significant difference between women and men with slight heterogeneity in a fixed effects model(HR 5 0.87, 95% CI: 0.85-0.89, p < 0.00001; I 2 5 26%, p 5 0.22, Fig. 2).…”

VATE: VAlidation of high TEchnology based on large database analysis by learning machine

“…Considering that, observational studies are essential to identify whether practice has changed appropriately, to document harms of therapy in a wider population, in patients of different age and with different comorbidities and to determine whether patients in routine practice are reaching the expected outcomes [17][18][19] with future science group www.futuremedicine.com the expected toxicity. However, when multiples RCTs within one tumor type and comparing over decades and worldwide different treatment agents, classes and subpopulations, are observed in a pooled analysis [20][21][22], the best of both research regimens is reached: high amount of patient's variability with high data quality.…”