Impact of timing of adjuvant chemotherapy on survival in stage III colon cancer: a population-based study

Abstract

Background: There is no consensus regarding the optimal time to initiate adjuvant chemotherapy after surgery for stage III colon cancer, and the relevant postoperative complications that cause delays in adjuvant chemotherapy are unknown.

Methods: Eligible patients aged ≥66 years who were diagnosed with stage III colon cancer from 1992 to 2008 were identified using the linked Surveillance, Epidemiology, and End Results-Medicare database. Kaplan-Meier analysis and a Cox proportional hazards model were utilized to evaluate the impact of the timing of adjuvant chemotherapy on overall survival (OS).

Results: A total of 18,491 patients were included. Delayed adjuvant chemotherapy was associated with worse OS (9-12 weeks: hazard ratio [HR] = 1.222, 95% confidence interval [CI] = 1.063-1.405; 13-16 weeks: HR = 1.252, 95% CI = 1.041-1.505; ≥ 17 weeks: HR = 1.969, 95% CI = 1.663-2.331). The efficacies of adjuvant chemotherapy within 5-8 weeks and ≤4 weeks were similar (HR = 1.045, 95% CI = 0.921-1.185). Compared with the non-chemotherapy group, chemotherapy initiated at ≥21 weeks did not significantly improve OS (HR = 0.882, 95% CI = 0.763-1.018). Patients with postoperative complications, particularly cardiac arrest, ostomy infection, shock, and septicemia, had a significantly higher risk of a 4- to 11-week delay in adjuvant chemotherapy (p < 0.05).

Conclusions: Adjuvant chemotherapy initiated within 8 weeks was acceptable for patients with stage III colon cancer. Delayed adjuvant chemotherapy after 8 weeks was significantly associated with worse OS. However, adjuvant chemotherapy might still be useful even with a delay of approximately 5 months. Moreover, postoperative complications were significantly associated with delayed adjuvant chemotherapy.

Keywords: Colon cancer; Postoperative complications; SEER-Medicare program; Stage III; Timing of adjuvant chemotherapy.

Fig. 1

Splines-based hazard ratio curve for identification of the effect of timing of chemotherapy on overall survival. The solid line presents the relationship (log hazard ratio) between timing of chemotherapy and overall survival, and the dotted line presents the corresponding 95% confidence limits

Fig. 2

Kaplan–Meier curve of the timing of chemotherapy and overall survival. The p value is derived from log-rank test for the overall comparison of overall survival between different timing of chemotherapy and non-chemotherapy group

Fig. 3

Hazard ratio plot for the relationship between timing of chemotherapy and overall survival compared with the non-chemotherapy group

Fig. 4

Kaplan–Meier curve of chemotherapy regimen and overall survival. The p value is derived from log-rank test for the overall comparison of overall survival between different chemotherapy regimens and non-chemotherapy group

Fig. 5

Hazard ratio plot for the relationship between timing of FOLFOX/CapeOX chemotherapy and overall survival compared with the non-chemotherapy group

Fig. 6

Association between postoperative complications and timing of adjuvant chemotherapy (AC) after surgical resection. Orange color bars present the timing of AC among patients with postoperative complications. Blue color bars present the timing of AC among patients without postoperative complications. “**” present a significant difference with p value < 0.01