Timing of adjuvant chemotherapy initiation and mortality among colon cancer patients at a safety-net health system

Abstract

Background: Prior studies reported survival benefits from early initiation of adjuvant chemotherapy for stage III colon cancer, but this evidence was derived from studies that may be sensitive to time-related biases. Therefore, we aimed to estimate the effect of initiating adjuvant chemotherapy ≤8 or ≤ 12 weeks on overall and disease-free survival among stage III colon cancer patients using a study design that helps address time-related biases.

Methods: We used institutional registry data from JPS Oncology and Infusion Center, a Comprehensive Community Cancer Program. Eligible patients were adults aged < 80 years, diagnosed with first primary stage III colon cancer between 2011 and 2017, and received surgical resection with curative intent. We emulated a target trial with sequential eligibility. We subsequently pooled the trials and estimated risk ratios (RRs) along with 95% confidence limits (CL) for all-cause mortality and recurrence or death at 5-years between initiators and non-initiators of adjuvant chemotherapy ≤8 or ≤ 12 weeks using pseudo-observations and a marginal structural model with stabilized inverse probability of treatment weights.

Results: Our study population comprised 222 (for assessing initiation ≤8 weeks) and 310 (for assessing initiation ≤12 weeks) observations, of whom the majority were racial/ethnic minorities (64-65%), or uninsured with or without enrollment in our hospital-based medical assistance program (68-71%). Initiation of adjuvant chemotherapy ≤8 weeks of surgical resection did not improve overall survival (RR for all-cause mortality = 1.04, 95% CL: 0.57, 1.92) or disease-free survival (RR for recurrence or death = 1.07, 95% CL: 0.61, 1.88). The results were similar for initiation of adjuvant chemotherapy ≤12 weeks of surgical resection.

Conclusions: Our results suggest that the overall and disease-free survival benefits of initiating adjuvant chemotherapy ≤8 or ≤ 12 weeks of surgical resection may be overestimated in prior studies, which may be attributable to time-related biases. Nevertheless, our estimates were imprecise and differences in population characteristics are an alternate explanation. Additional studies that address time-related biases are needed to clarify our findings.

Keywords: Adjuvant chemotherapy; Disease-free survival; Mortality; Prognosis; Quality of care; Timing; colon cancer.

Fig. 1

Marginal survival curves^a for initiation or no initiation of adjuvant chemotherapy ≤8 weeks of surgical resection for stage III colon cancer patients. A Overall survival. B Disease-free survival. (Adjusted for age, sex, race/ethnicity, insurance status, marital status, National Cancer Institue comorbidity index, body mass index, tumor grade, and surgical procedures)

Fig. 2

Marginal survival curves^a for initiation or no initiation of adjuvant chemotherapy ≤12 weeks of surgical resection for stage III colon cancer patients. A Overall survival. B Disease-free survival. (Adjusted for age, sex, race/ethnicity, insurance status, marital status, National Cancer Institue comorbidity index, body mass index, tumor grade, and surgical procedures)