Outcomes after colorectal-cancer surgery are no better with more- versus less-intensive surveillance, according to two new studies in the May 22/29 issue of JAMA.
"Previous small-scale trials suggested a benefit to intensive follow-up," said Dr. Andrew G. Renehan from the University of Manchester, U.K., who worked on one of the studies, called COLOFOL. "This study, the largest to-date, strongly suggests" there is no such benefit, he told Reuters Health by email.
In COLOFOL, 2,509 patients who underwent curative surgery for stage II or III colorectal cancer were randomly assigned to follow-up with computed tomography and carcinoembryonic antigen (CEA) at high frequency (six, 12, 18, 24 and 36 months) or low frequency (12 and 36 months).
Five-year overall mortality did not differ significantly between high-frequency (13.0%) and low-frequency follow-up (14.1%), the researchers report.
Similarly, there were no significant differences between the groups in five-year colorectal-cancer-specific mortality rates (10.6% vs. 11.4%, respectively) or in risk of colorectal-cancer-specific recurrence (21.6% vs. 19.4%, respectively).
Results were similar when stratified by cancer stage and when patients with rectal cancer were considered separately.
Many physicians and patients "believe that high-frequency testing after cancer treatment is good - early detection of recurrence, etc. - but this trial goes against this tenet," Dr. Renehan said. "We now have the challenge to reverse that culture."
In the second study, Dr. George J. Chang from the University of Texas MD Anderson Cancer Center in Houston and colleagues reviewed data from the National Cancer Database to investigate the association between surveillance intensity and detection of colorectal cancer recurrence and survival.
Among more than 8,500 patients with stage I, II, III colorectal cancer, there was no significant association between surveillance intensity and detection of colorectal-cancer recurrence. The median time to detection of any recurrence was virtually the same for high-intensity imaging or CEA and low-intensity imaging or CEA.
Similarly, there were no significant differences in rates of resection for recurrence at three or five years or in five- and seven-year overall survival rates based on imaging or CEA intensity.
Dr. Chang told Reuters Health by email, "Our current U.S. guidelines for surveillance testing may be recommending more-frequent testing than necessary. During follow-up there are many concerns that should be addressed, including testing for asymptomatic recurrence, managing treatment-related toxicity, promoting healthy lifestyles and secondary prevention, and addressing psychosocial needs."
"More testing does not lead to better outcomes," he said. "Currently our approach to surveillance is based on little information about an individual patient's disease and risk. As advances continue to be made in the field, I anticipate that we will move towards a more individualized approach that incorporates better technology for assessing the presence of minimal residual disease that may signal the risk for subsequent disease recurrence. At present, circulating tumor DNA is one such promising approach."
Dr. Chang added, "There is tremendous variation in the guidelines for surveillance testing around the world, and this variation is due to limited evidence. In addition, there is tremendous variation in how surveillance is performed by individual providers. However, the frequency of follow-up testing should be tailored to underlying recurrence risk. For most patients, there may be limited benefit to more-frequent testing, and optimal follow-up should consider the patient's underlying disease stage, potential for treatment of recurrence, and their personal preferences, values, and needs."
Dr. Hanna K. Sanoff from the University of North Carolina at Chapel Hill, whose editorial accompanied the reports, said by email, "These studies, and the recent FACS trial, all challenge our notion that earlier detection is better when it comes to getting patients to successful surgery for recurrent metastatic colorectal cancer."
"Surgical resection of oligometastatic colorectal cancer is unequivocally a crucial part of the care for patients with colorectal cancer and a major part of why survival for advanced colorectal cancer has improved in recent years," she said. "Yet all recent evidence, including from these two JAMA papers, has found that doing imaging on a 6-month basis in an effort to get more people to surgery for recurrent cancer doesn't affect survival in a meaningful way compared with less-frequent imaging."
"It may well be that the biology of the cancer plays the most important role in determining outcomes," she suggested. "There are increasingly robust data to support that notion. For example, patients whose cancer harbors RAS or RAF mutations are known to have inferior outcomes following resection of colorectal cancer liver metastases than those without such mutations."
"While intuitively it makes sense that patients at higher risk of recurrence should have more-frequent imaging, there really are no data that doing that improves outcomes," Dr. Sanoff concluded. "In fact, what data we do have all supports less-frequent imaging as equally effective. So, my practice is to scan patients annually after curative resection of stage II-III colorectal cancer surgery, using interval scans only in the case of symptoms of concern."
She added, "In order to improve outcomes for colorectal cancer survivors, we should shift our focus from a higher surveillance intensity to ensuring survivors are counseled on adjunctive things they can do to decrease recurrence, such as exercise, supplemental aspirin, (and) dietary modifications. We also need to enroll patients in upcoming clinical trials that will incorporate novel means of assessing for residual or recurrent disease, such as circulating tumor DNA."
SOURCE: https://bit.ly/2s3rGZy, https://bit.ly/2s5Ve8a and https://bit.ly/2s32i6q
JAMA 2018.
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