NEW YORK (360Dx) – Increased follow-up surveillance of patients treated for colorectal cancer did not significantly improve their outcomes, researchers said in a pair of studies published on Tuesday in the Journal of the American Medical Association.
Together, the studies cast a new light on how aggressively colorectal cancer patients should be tested with multislice contrast-enhanced CT of the thorax and abdomen, and serum carcinoembryonic antigen (CEA) following treatment, and whether guidelines for follow-up care need to be reconsidered.
In one study, researchers from Sweden, Denmark, and the US determined that increased surveillance of patients who had been treated for stage II or III colorectal cancer did not significantly increase the rate of earlier detection of cancer recurrence or improved survival.
Analyzing data from more than 2,500 patients, the study found that the five-year cancer-specific mortality rate was 10.6 percent among patients who underwent high-frequency surveillance compared to 11.4 percent among those who underwent low-frequency surveillance. Meantime, the risk of detected colorectal cancer-specific recurrence was 21.6 percent for the high-frequency group compared to 19.4 percent with the low-frequency group.
Overall mortality similarly did not significantly vary between the two groups — the five-year overall mortality rate for the high-frequency group, which comprised 1,253 patients, was 13 percent compared to 14.1 percent for the low-frequency group, which comprised 1,256 patients.
In their report the researchers said that while treatments for colorectal cancer have dramatically improved since 2005 and have subsequently improved patient outcomes, little research has been done to evaluate whether high-frequency surveillance of patients has clinical benefits compared to low-frequency surveillance. The systematic reviews that have been done, as well as a randomized trial, looking at potential benefits of high-frequency surveillance provided inconclusive evidence.
The researchers looked at 2,509 patients with stage II or III colorectal cancer treated at 24 centers in Sweden, Denmark, and Uruguay between January 2006 and December 2010 and followed up for five years. The patients were randomized to the high-frequency group and low-frequency group. The high-frequency group was required to have follow-up CT scans and serum carcinoembryonic antigen (CEA) at six, 12, 18, 24, and 36 months. The low-frequency group was required to have follow-up testing at 12 and 36 months after surgery.
The primary outcomes for the study were the five-year overall mortality rate and colorectal cancer-specific mortality rates. The secondary outcome was the colorectal cancer-specific recurrence rate during five years of follow-up. Both intention-to-treat and per-protocol analyses were performed.
While the researchers found little differences in the overall mortality, cancer-specific mortality, and cancer-specific recurrence rates between the high-frequency and low-frequency groups, they noted that the rate of cancer-specific recurrence was higher for the high-frequency group during the time intervals in which the low-frequency group had no examinations — at the six-month, 18-month, and 24-month periods.
They also pointed out that their data was in line with findings from the Follow-up After Colorectal Surgery trial and a 2016 meta-analysis. The FACS trial found that the number of deaths were not significantly different between patient groups that received intensive monitoring with CT, CEA, and combined CT-CEA testing, and patient groups that received minimal monitoring.
The 2016 meta-analysis also did not find any overall survival benefit from increased patient follow-up after curative surgery for colorectal cancer.
In a separate study published this week, researchers led by a team at the University of Texas MD Anderson Cancer Center found that there was no association between intensity of post-treatment surveillance and detection of recurrence or overall survival in patients with stage I, II, or III colorectal cancer.
Specifically, in a retrospective analysis of data from 8,529 patients, they found that the median time to recurrence detection was 15.1 months for high-intensity imaging compared to 16 months for low-intensity imaging. The median time for any recurrence detection was 15.9 months for high-intensity CEA testing compared to 15.3 months for low-intensity CEA testing.
Additionally, the median time to locoregional recurrence detection by high-intensity imaging was 12.2 months vs. 13.7 months for low-intensity imaging; and 11.3 months for high-intensity CEA testing compared to 14.1 months for low-intensity CEA testing.
The median time to detection for distant recurrence was 16 months for high-intensity imaging compared to 16.6 months for low-intensity imaging, and 17 months for high-intensity CEA testing compared to 15.5 months for low-intensity CEA testing.
The researchers also reported no significant difference in the proportion of patients who underwent resection for recurrence at three or five years by surveillance intensity based on imaging or CEA testing.
"In addition, five- and seven-year overall survival rates did not differ significantly based on imaging or CEA intensity," they wrote.
They pointed to several possible reasons for the lack of an association between surveillance intensity and overall survival, including the low event rate of surgical treatments after initial treatments have failed — sometimes called salvage surgery — observed in the study and in recently reported trials.
"The study may be underpowered to detect a difference in overall survival based on resection rates, although the absolute difference in overall survival would be expected to be small," the researchers said.
They also noted limitations in their study: it is a retrospective cohort study, and patients could not be randomized, nor could they account for individual decision-making of testing frequency.
Nonetheless, the findings run counter to historical data and provide fodder to reconsider current guideline recommendations on surveillance of colorectal cancer patients, George Chang, a professor of surgical oncology and of health services research at MD Anderson, said in a statement.
"As we learn more about the biology and heterogeneity of colorectal cancer, the answer is not always another test," he added. "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."
Rather than increased surveillance for all patients, he added, a more tailored approach may be required.