Effect of More vs Less Frequent Follow-up Testing on Overall and Colorectal Cancer-Specific Mortality in Patients With Stage II or III Colorectal Cancer: The COLOFOL Randomized Clinical Trial

Abstract

Importance: Intensive follow-up of patients after curative surgery for colorectal cancer is common in clinical practice, but evidence of a survival benefit is limited.

Objective: To examine overall mortality, colorectal cancer-specific mortality, and colorectal cancer-specific recurrence rates among patients with stage II or III colorectal cancer who were randomized after curative surgery to 2 alternative schedules for follow-up testing with computed tomography and carcinoembryonic antigen.

Design, setting, and participants: Unblinded randomized trial including 2509 patients with stage II or III colorectal cancer treated at 24 centers in Sweden, Denmark, and Uruguay from January 2006 through December 2010 and followed up for 5 years; follow-up ended on December 31, 2015.

Interventions: Patients were randomized either to follow-up testing with computed tomography of the thorax and abdomen and serum carcinoembryonic antigen at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; n = 1253 patients) or at 12 and 36 months after surgery (low-frequency group; n = 1256 patients).

Main outcomes and measures: The primary outcomes were 5-year overall mortality and colorectal cancer-specific mortality rates. The secondary outcome was the colorectal cancer-specific recurrence rate. Both intention-to-treat and per-protocol analyses were performed.

Results: Among 2555 patients who were randomized, 2509 were included in the intention-to-treat analysis (mean age, 63.5 years; 1128 women [45%]) and 2365 (94.3%) completed the trial. The 5-year overall patient mortality rate in the high-frequency group was 13.0% (161/1253) compared with 14.1% (174/1256) in the low-frequency group (risk difference, 1.1% [95% CI, -1.6% to 3.8%]; P = .43). The 5-year colorectal cancer-specific mortality rate in the high-frequency group was 10.6% (128/1248) compared with 11.4% (137/1250) in the low-frequency group (risk difference, 0.8% [95% CI, -1.7% to 3.3%]; P = .52). The colorectal cancer-specific recurrence rate was 21.6% (265/1248) in the high-frequency group compared with 19.4% (238/1250) in the low-frequency group (risk difference, 2.2% [95% CI, -1.0% to 5.4%]; P = .15).

Conclusions and relevance: Among patients with stage II or III colorectal cancer, follow-up testing with computed tomography and carcinoembryonic antigen more frequently compared with less frequently did not result in a significant rate reduction in 5-year overall mortality or colorectal cancer-specific mortality.

Trial registration: clinicaltrials.gov Identifier: NCT00225641.

Figure 1.. Patient Flow Through the COLOFOL Trial

Figure 2.. Primary Outcome of Overall Mortality by Time From Colorectal Cancer Surgery for the Intention-to-Treat and Per-Protocol Analyses

The median follow-up time was 5 years (interquartile range, 5-5 years) in each study group. Tinted area indicates 95% confidence interval.

Figure 3.. Primary Outcome of Colorectal Cancer–Specific Mortality by Time From Colorectal Cancer Surgery for the Intention-to-Treat and Per-Protocol Analyses

The median follow-up time was 5 years (interquartile range, 5-5 years) in each study group. The No. at risk sample sizes differ from Figure 2 because 11 patients (6 from the low-frequency group and 5 from the high-frequency group) were excluded due to missing recurrence data. Tinted area indicates 95% confidence interval.

Figure 4.. Secondary Outcome of Colorectal Cancer–Specific Recurrence

The median follow-up time was 5 years (interquartile range, 4.6-5.0 years) in the high-frequency group and 5 years (5.0-5.0 years) in the low-frequency group. The No. at risk sample sizes differ from Figure 2 because 11 patients (6 from the low-frequency group and 5 from the high-frequency group) were excluded due to missing recurrence data. Tinted area indicates 95% confidence interval.