Physicians are underestimating the risk for recurrence in more than a third of patients who have undergone resection of a gastrointestinal stromal tumor (GIST). The result is that many patients do not receive the recommended therapy of adjuvant imatinib (Gleevec), and therefore face an increased risk for recurrence or death, according to American investigators.
"These findings suggest a need for improved education for physicians on risk assessment and risk reduction," they conclude.
The research was published online July 23 in JAMA Oncology.
One issue highlighted by the investigators is that physicians are not using established risk-assessment tools. The risk for recurrence can be assessed with a number of different tools, the most widely accepted of which is the Revised National Institute of Health (NIH) Consensus Criteria.
"I think there are a couple of things that are happening here," study investigator Alexander R. Macalalad, MD, from Analysis Group Inc. in Montreal, told Medscape Medical News.
"One is that GIST is a relatively rare cancer. There isn't a lot of volume there for most oncologists, and so there's a relative unfamiliarity with these tools," he pointed out.
"The other thing is that there are a number of tools out there and they are all slightly different, so they give the impression that there isn't a standard in scoring these patients' risk," he added.
Consequently, physicians rely on their own experience, which Dr Macalalad argued is "going to be less accurate than tools that have been developed over thousands of patients."
In addition, although a large proportion of physicians use the tools, physicians "often second-guess them because there's a perception that these tools aren't very accurate, just because there's so many of them and they are not standardized," he said.
Interestingly, the investigators found that risk for recurrence calculated by the major risk-assessment tools was consistent. "They all agreed that patients were either at high risk or not at high risk, so whatever tool the physician used, they would have come up with the same answer," Dr Macalalad explained.
"What we're hoping with this study is that we can encourage physicians to use the one they're most comfortable with for now and, if it goes against their own thinking, they can give it the benefit of the doubt," he noted.
Study Details
For their study, Dr Macalalad and colleagues invited American physicians to participate in a retrospective, observational medical record review of adults diagnosed with primary resectable c-KIT-positive GIST who had undergone primary tumor resection.
The majority of the 109 physicians who took part in the study were experienced oncologists. About one-third (32%) had been in practice for 5 to 10 years, and 56% had been in practice for more than 10 years. Each oncologist had treated a median of 30 GIST patients during the previous 10 years.
The analysis involved 506 patients. Median age was 59 years, and median follow-up was 15 months. Resection was performed a median of 12 days after GIST diagnosis.
On the basis of the Revised NIH Consensus Criteria, 65.8% of patients were classified as being at high risk for recurrence, 8.7% were classified as being at intermediate risk, 10.5% were classified as being at low risk, and 15.0% were classified as being at very low risk for recurrence.
According to the medical records, physicians underestimated the risk for recurrence for 37.5% of patients, correctly estimated the risk for 53.4%, and overestimated the risk for 9.1%.
Patients whose risk was underestimated were significantly more likely than those whose risk was correctly estimated to have a tumor size of 6 to 10 cm (27.8% vs 46.8%; P < .001) and to have a mitotic count of 6 to 10 per 50 high-power fields (22.8% vs 64.7%; P < .001). However, they were less likely to have a gastric tumor (30.0% vs 49.7%; P < .001).
Patients Not Receiving Recommended Treatment
Because adjuvant therapy with the tyrosine kinase inhibitor imatinib helps improve recurrence-free survival in patients at high risk for recurrence, at least 3 years of treatment after primary GIST resection is recommended by the National Comprehensive Cancer Network.
For high-risk patients, those in the underestimated group were less likely than those in the correctly estimated group to receive the recommended 3 years of adjuvant treatment (36.1% vs 65.9%; P < .001), Dr Macalalad and colleagues report. And those in the underestimated group were more likely to receive no adjuvant therapy than those in the correctly estimated group (21.3% vs 8.5%; P < .001).
The investigators highlight the fact that for high-risk patients, the risk for recurrence and/or death was significantly lower with at least 3 years of adjuvant treatment than with less than 3 years of treatment (adjusted hazard ratio, 0.29; P < .001).
The underestimation of risk for recurrence often occurred in borderline cases in which the tumor size was relatively small or the mitotic count was relatively low, Dr Macalalad told Medscape Medical News.
"I think physicians underappreciate how much risk can change if that type of tumor is found, say, outside of the stomach, in the small intestine, or in another area. The same tumor can double the risk of recurrence, and those nuances are may be underappreciated by the physician who may not see a lot of GIST," he noted.
"I think the tumor just seemed too small or too benign to really recur, and it caught the physician off guard," he explained. "Becoming more aligned on these tools can hopefully guide them to recognize that some of these benign-looking tumors really do have a recurrence potential, and they need to give adjuvant treatment for that."
This study was sponsored by Novartis, the manufacturer of imatinib. Dr Macalalad and three of his coauthors are employees of Analysis Group Inc., which has received consultancy fees from Novartis. Two of his coauthors are employees of Novartis. Coauthor Anthony Conley, MD, from the University of Texas M.D. Anderson Cancer Center in Houston, reports unpaid consultancy for Novartis.
JAMA Oncol. Published online July 23, 2015. Abstract
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