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Frequent colorectal cancer follow-up does not improve recurrence, survival
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More frequent follow-up testing for patients with colorectal cancer did not improve time to recurrence or survival, according to two studies published in JAMA.
“After completion of definitive treatment [for colorectal cancer], surveillance is recommended with the goal of improving disease-specific and overall survival by detecting disease recurrence or a second primary cancer early, such that a patient has an opportunity for potentially curative surgery,” Rebecca A. Snyder, MD, MPH, surgical oncologist at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “However, the optimal surveillance strategy is unknown, and recent data from randomized trials have not demonstrated significant survival benefit from intensive follow-up.”
U.S. data
In a nonrandomized, observational study, Snyder and colleagues assessed 8,529 patients treated for stage I, stage II or stage III colorectal cancer from 2006 to 2007. The researchers used data from the National Cancer Database on 1,175 U.S. facilities and followed patients through December 2014.
Researchers assessed the impact of intensity of imaging and carcinoembryonic antigen (CEA) surveillance testing on colorectal cancer-related recurrence, resection for recurrent disease and OS.
During a 3-year posttreatment observational period, patients underwent a mean of 2.9 (95% CI, 2.8-2.9) imaging scans and a mean of 4.3 (95% CI, 4.2-4.4) CEA tests when treated at high-intensity facilities, compared with a mean of 1.6 (95% CI, 1.6-1.7) imaging scans and a mean of 1.6 CEA tests at low-intensity facilities.
Imaging and CEA testing frequency did not appear associated with cancer recurrence outcomes.
Median time to detection of recurrence was 15.1 months for high-intensity imaging surveillance compared with 16 months for low-intensity imaging surveillance (HR = 0.99; 95% CI, 0.9-1.09), and 15.9 months for high-intensity CEA testing compared with 15.3 months for low-intensity CEA testing (HR = 1; 95% CI 0.9-1.11).
Researchers did not observe a difference in resection for cancer recurrence between high- and low-intensity imaging (HR = 1.22; 95% CI, 0.99-1.51) or between high- and low-intensity CEA testing (HR = 1.12; 95% CI, 0.91-1.39).
Results showed similar null associations for OS when comparing patients treated at high-intensity vs. low-intensity facilities for imaging (HR = 1.01; 95% CI, 0.94-1.08) and CEA testing (HR = 0.96; 95% CI, 0.89-1.03).
“Based on these data and the recent [Follow-up After Colorectal Surgery] trial, current National Comprehensive Cancer Network guideline recommendations (CT testing every 6 months for 3 years) could be considered overtesting given the absence of improvement in recurrence detection or survival,” Snyder and colleagues wrote. “Moreover, these data suggest that the recommendation of two CT scans in the first 3 years and CEA testing every 6 months in the first 3 years by the National Institute for Health and Care Excellence in the United Kingdom are appropriate.”
COLOFOL trial
In another study published in JAMA, Peer Wille-Jørgensen, DMSc, of the Abdominal Disease Center at Bispebjerg Hospital and the Danish Colorectal Cancer Group, and colleagues also found that more frequent follow-up did not appear to improve survival.
The randomized COLOFOL trial — conducted at 24 centers in Denmark, Sweden and Uruguay — included 2,509 patients with stage II or stage III colorectal cancer who underwent surgery and adjuvant therapy.
Wille-Jørgensen and colleagues randomly assigned patients to receive thorax and abdomen CT and serum CEA tests at a high frequency — which included test at 6 months, 12 months, 18 months, 24 months and 36 months — or at a low frequency, at 12 months and 36 months after surgery.
Five-year mortality rate and colorectal cancer-related mortality rate served as the primary endpoints. Colorectal cancer recurrence served as a secondary endpoint.
Researchers did not observe a significant difference among the endpoints between the high-frequency and low-frequency groups. For the high-frequency group compared with the low-frequency group:
5-year overall mortality rate was 13% vs. 14.1% (risk difference, 1.1 percentage points; 95% CI, –1.6 to 3.8);
5-year colorectal cancer-specific mortality was 10.6% vs. 11.4% (risk difference, 0.8 percentage points; 95% CI, –1.7 to 3.3); and
colorectal cancer-specific recurrence rate was 21.6% vs. 19.4% (risk difference, 2.2 percentage points; 95% CI, –1 to 5.4).
The study limitations included possible nonadherence to study protocol and inability to blind participants to treatment assignment.
Impact on guidelines
In an accompanying editorial, Hanna K. Sanoff, MD, section chief of gastrointestinal medical oncology and associate professor of medicine at the University of North Carolina at Chapel Hill, as well as clinic medical director of the cancer prevention and control, and gastrointestinal oncology programs of North Carolina Cancer Hospital, discussed whether the existing body of evidence is enough to change practice guidelines.
National Cancer Database study should not be considered precise estimates of the effect of surveillance on survival; however, as gold-standard randomized clinical trial evidence is unlikely to become available, decisions must be made on the basis of these imperfect, although methodologically sound, reports,” Sanoff said. “In combination with data from the Follow-up After Colorectal Surgery trial that found little difference in survival between minimal surveillance and what in the context of the COLOFOL trial and the National Cancer Database study would be considered a high-intensity strategy, there is now a considerable body of evidence that imaging and CEA testing more often than every year does little to improve survival in a meaningful way.”
Sanoff recommended that the guidelines be reevaluated in the context of these data.
“Surveillance that incorporates a more nuanced assessment of cancer biology will ultimately be needed to further improve cure rates for patients with stage II and III colorectal cancer,” she added. – by Cassie Homer
Disclosures: Snyder, Wille-Jørgensen and Sanoff report no relevant financial disclosures. Please see the studies for all other authors’ relevant financial disclosures.
Perspective
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NCCN guidelines — version 2.2018 — on surveillance for recurrence after surgery for stage II/stage III colon cancer include history and physical exam every 3 to 6 months for 2 years, then every 6 months for a total of 5 years; CEA every 3 to 6 months for 2 years, then every 6 months for a total of 5 years; chest/abdomen/pelvic CT every 6 to 12 months for a total of 5 years; and colonoscopy in 1 year, or in 3 to 6 months if there was no preoperative colonoscopy due to obstructing lesion. If there is an advanced adenoma, the guidelines state to repeat colonoscopy in 1 year and, if there is no advanced adenoma, repeat in 3 years, then every 5 years.
Similar NCCN guidelines exist for rectal cancer — version 1.2018.
Mant and colleagues presented a randomized controlled trial at the 2013 ASCO Annual Meeting called Follow-up After Colorectal Surgery, or FACS, that studied the effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer. The analysis included 1,202 patients from 39 U.K. hospitals and compared minimal imaging — symptomatic follow-up plus single CT at 12 to 18 months — with intensive imaging CT every 6 months for 2 years and annually for another 3 years, along with no CEA or with CEA every 3 months for 2 years then every 6 months up to 5 years. Researchers found that the rate of detection of recurrence treated surgically with curative intent was three times higher in the more intensive follow-up arms compared with the minimum follow-up arm. The study found no difference in colorectal cancer deaths nor overall deaths between the minimum compared with the intensive follow-up arms. Because of the higher rate of detection of recurrence with the possibility for cure, current practice has continued to use more intensive surveillance early, especially for stage III colorectal cancer.
In these two new publications in JAMA by Wille-Jorgensen and colleagues and Snyder and colleagues, new evidence is provided regarding the issue of surveillance and intensive follow-up after curative surgery for colorectal cancer. Researchers of COLOFOL found no difference in OS or colorectal cancer-specific mortality between high-frequency or low-frequency surveillance. In their retrospective trial, Snyder and colleagues found no association between the intensity of surveillance and detection of recurrence. Both studies maintained that there were still no differences in the outcome measures in subgroup analyses for patients with stage III colorectal cancer. These new studies add to the body of knowledge regarding postsurgery surveillance for early-stage colorectal cancer and will likely impact on practice patterns for stage II and III patients.
For those at highest risk for recurrence, the data need to be examined more closely and clearly for patients with T4 or N2 disease, or BRAF or KRAS mutations. Earlier detection may not matter due to biology, but it will be important to find out if any and which subgroups may benefit from earlier detection of recurrence in terms of potential resectability and cure. For those at lower-risk stage III disease and stage II disease, practice may shift to the less frequent imaging surveillance.
Mant D, et al. Abstract 3500. Presented at ASCO Annual Meeting; May 31-June 4, 2013; Chicago.
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