Intensive surveillance after curative surgery for non-metastatic colorectal cancer (CRC) was not effective in reducing time to detection of recurrence, 5-year overall mortality, or 5-year CRC-specific mortality in patients with stage I, II, or III disease, two studies showed.
In the unblinded, randomized multicenter COLOFOL trial in 2,509 patients with stage II or III CRC, there was no significant difference in the 5-year overall mortality rate when the frequency of follow-up testing with computed tomography (CT) and serum carcinoembryonic antigen (CEA) was increased from two to five exams in the 3-year period after surgery (13.0% versus 14.1%, respectively; P=0.43).
Similarly, there was only a 0.8% difference in CRC-specific mortality rate at 5 years with high-frequency compared with low-frequency testing (10.6% versus 11.4%; P=0.52), according to Henrik T. Sørensen, DMSc, of Aarhus University Hospital in Denmark, and colleagues.
There was a 2.2% risk difference in the incidence of recurrence detection between surveillance strategies (21.6% versus 19.4%; P=0.15), but this did not translate into a reduced mortality rate, the study authors reported online in JAMA.
The investigators noted that the trial’s low-intensity follow-up testing was less frequent than recommended in guidelines from the National Comprehensive Cancer Network(NCCN) and the American Society of Clinical Oncology.
“The results of this trial should be considered as the evidence base for updating these clinical guidelines,” the team wrote.
The data extend former research on the usefulness of postoperative colorectal cancer follow-up, and correspond with the Follow-up After Colorectal Surgery (FACS) trial and a 2016 meta-analysis, the authors noted.
The COLOFOL study group, established in 2004, included 24 participating recruitment centers in Denmark, Sweden, and Uruguay. Study follow-up ended on December 31, 2015.
Patients were randomized to either high-frequency follow-up with CT of the thorax and abdomen and CEA testing at 6, 12, 18, 24, and 36 months after surgery (1,253 patients) or low-frequency surveillance at 12 and 36 months after surgery (1,256 patients). A total of 2,365 patients completed the trial; mean age was 63.5, and 45% (1,128) were female.
Limitations of the COLOFOL trial, the researchers said, include the design, in which patients and physicians were not blinded to the frequency of follow-up examinations, and the long study period, which may have affected adherence to the protocol.
In a second study in the same issue of the journal, a retrospective cohort analysis of data from the Commission on Cancer (CoC) merged with records from the U.S. National Cancer Database (NCDB) found no association between the intensity of surveillance and time to detection of CRC recurrence or overall survival in 8,529 patients treated for stage I, II, or III disease.
Time to detection of recurrence was not significantly different between patients treated at high- and low-imaging intensity facilities (hazard ratio [HR] 0.99) and at high- and low-CEA-intensity facilities (HR 1.00), said George J. Chang, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues — all of whom are members of the Alliance for Clinical Trials in Oncology Network Cancer Surveillance Optimization Working Group.
Facilities considered high-intensity performed a mean of 2.87 imaging and 4.31 CEA tests in the 3 years following resection. Low-intensity facilities performed a mean of 1.63 tests in the 3-year testing window for both imaging and CEA.
A comparison of both imaging and CEA intensity showed no significant association with the risk of surgical resection of recurrence (0.67% and 0.38%, respectively).
The median time to recurrence for patients in the high-intensity imaging surveillance group was 15.1 months versus 16.0 months in the low-intensity group. For patients in the high-intensity CEA surveillance group, median time to recurrence was 15.9 months versus 15.3 months in the low-intensity group.
There was no difference in overall survival for either surveillance strategy, with rates of 65.6% at 7 years in the high-intensity imaging group and 65.5% in the low-intensity imaging group. A similar lack of difference was observed by CEA intensity.
In a subgroup analysis comparing patients treated at facilities in the lowest- versus highest-intensity quartile, there was no significant survival advantage with either imaging (HR 1.09) or CEA (HR 0.99).
“There is limited evidence to inform the current guidelines for follow-up testing after curative treatment of colon and rectal cancer, and this has resulted in large variations in surveillance guidelines,” Chang said in a news release from MD Anderson. “These findings differ from historical data and argue to reconsider current guideline recommendations in the U.S.”
Based on their study results and the FACS trial, Chang et al said that current NCCN guideline recommendations for CT testing every 6 months for 3 years could be considered overtesting given the absence of survival improvement in or increased detection of recurrence.
“In addition to added costs, unnecessary testing in cancer patients can lead to treatment toxicity, increased patient anxiety, and the potential for false positives, which can lead to patient harm,” said Chang. “The data argue that in many cases, a less-intensive surveillance may be a better approach for patients.”
According to the authors, more appropriate recommendations from the National Institute for Health and Care Excellence in the United Kingdom, which are supported by data, call for two CT scans and CEA testing every 6 months in the first 3 years.
Limitations of this study, the researchers said, include the fact that data were collected on up to 10 patients for each of 1,175 CoC facilities regardless of volume, so low-volume facilities may be over-represented.
Writing in an accompanying editorial, Hanna K. Sanoff, MD, of the University of North Carolina at Chapel Hill, said both studies showed that less frequent surveillance did not compromise long-term outcomes. This was seen even when the follow-up frequency was less often than recommended by most expert guidelines, she pointed out.
Current guidelines should be re-evaluated, Sanoff said: “The potential harms of more frequent testing include distress, radiation exposure, and a financial burden on both patients and society. 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.”
Journal of the American Medical Association
Source Reference: Sørensen HT, et al “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” JAMA 2018; 319(20): 2095-2103.
Journal of the American Medical Association (JAMA)
Source Reference: Snyder RA, et al “Association between intensity of posttreatment surveillance testing and detection of recurrence in patients with colorectal cancer” JAMA 2018; 319(20): 2104-2115.
Journal of the American Medical Association (JAMA)
Source Reference: Sanoff, HK “Best evidence supports annual surveillance for resected colorectal cancer” JAMA 2018; 319(20): 2083-2085.