Physicians underestimate risk of gastrointestinal stromal tumor recurrence

Last Updated: 2015-07-30

By Will Boggs MD

NEW YORK (Reuters Health) - In more than a third of patients with gastrointestinal stromal tumor (GIST), physicians underestimate the risk of recurrence, often resulting in shorter adjuvant therapy, according to a retrospective study.

"Given that there is no single risk-stratification system for these patients, we hypothesized that there would be underestimation of risk for borderline cases where the systems might differ in their assessment of risk, but instead we found systematic underestimation of risk even among patients assessed to be at high risk no matter what risk-stratification system we used," Anne Guerin, from the Analysis Group, Montreal, Quebec, Canada, told Reuters Health by email.

Recurrence of GIST is common, even with complete resection, and the National Comprehensive Cancer Network (NCCN) recommends that patients at high risk of recurrence receive adjuvant imatinib (Gleevec, Novartis) for at least 36 months following resection.

Guerin and colleagues used information on 506 patients with GIST from 109 oncologists to evaluate how well the physicians assessed the risk of tumor recurrence, the impact of risk underestimation on planned adjuvant therapy duration, and the association between planned adjuvant therapy duration and relapse-free survival in high-risk patients.

Most oncologists had been in practice for more than 10 years, mainly in private practice in urban settings, according to the July 23 JAMA Oncology online report.

Based on Revised National Institutes of Health (NIH) Consensus Criteria, 65.8% of the patients were at high risk of recurrence, 8.7% were at intermediate risk, 10.5% were at low risk, and 15.0% were at very low risk.

Compared with these risk assignments, physicians were right most of the time (53.4%), but they underestimated the risk for 37.5% of patients and overestimated the risk for 9.1%.

Among intermediate-risk patients, only 27.3% in the not-underestimated group had a treatment plan with no adjuvant therapy, compared with 81.8% of patients in the underestimated group (p=0.003).

Among high-risk patients, significantly more patients in the not-underestimated group (65.9%) than in the underestimated group (36.1%) had a treatment plan of three or more years of adjuvant therapy (p=0.02). On the other hand, 11.0% of not-underestimated patients had a treatment plan of one to three years of adjuvant therapy, compared with 21.3% of underestimated patients (p=0.001).

After three years of follow-up, relapse-free survival rates for high-risk patients were lower for patients with underestimated risk (38.8%) than for patients whose risk was not underestimated (71.2%).

After adjusting for multiple factors, planned adjuvant treatment duration of at least three years was associated with a 71% lower risk of recurrence compared with shorter-duration adjuvant treatment.

"It is important to accurately assess the risk of recurrence among patients who undergo GIST resection," Guerin said. "Unfortunately, a significant proportion of patients in our study had an assessment which underestimated their risk of recurrence."

She reiterated, "It is important to give patients at high risk of recurrence three years of adjuvant treatment. Many patients in our study with unrecognized high risk of recurrence were not given sufficient adjuvant treatment, and the patients with insufficient adjuvant treatment had significantly shorter recurrence-free survival compared with those who received at least three years of adjuvant treatment."

"One of the strengths of this study is that we invited a broad range of U.S. community oncologists to participate online in this study, many of whom weren't affiliated with academic medical centers and would typically have few opportunities to participate in these kinds of studies," Guerin added. "As a consequence, we were able to quickly and efficiently collect information on a sizable number of GIST patients, despite the rarity of this disease. We were able to get an idea of real-world practice patterns to treat GIST patients, and we identified opportunities to improve the quality of care that these patients receive."

Dr. Heikki Joensuu, from the University of Helsinki, Finland, wrote an invited commentary related to this report. He told Reuters Health by email, "Some difference of opinion in GIST risk estimation is expected, but the proportion of GIST patients who had their risk underestimated -- more than a third -- is unexpectedly high."

"At least one of the validated risk-stratification schemes needs to be consulted to identify the GIST patients who most likely benefit from adjuvant imatinib," Dr. Joensuu said. "The most accurate available instruments are the Prognostic Heat Maps, the Armed Forces Institute of Pathology (AFIP) scheme, and the Revised National Institutes of Health Consensus Criteria."

Better education for physicians could include "attending an educational lecture on the topic or simply reading the few key publications," Dr. Joensuu said. "An educational website could be useful."

"Mutation analysis of GIST is important to carry out to identify the few mutations that confer imatinib resistance," Dr. Joensuu added. "Most patients who have no mutation in KIT or PDGFRA do not benefit from adjuvant imatinib."

Dr. Danielle A. Bischof, from Mount Sinai Hospital, Toronto, Ontario, Canada, recently reviewed adherence to guidelines for adjuvant imatinib therapy for GIST. She told Reuters Health by email, "Clear reporting of risk of recurrence using revised NIH consensus criteria on synoptic pathology reports for all patients undergoing surgery for GIST would take the guess-work out of risk stratification for oncologists. A consensus statement with clear recommendations on risk stratification and indications for adjuvant imatinib may also be of benefit as well."

"There are well-defined criteria to determine recurrence risk for GIST following surgery," Dr. Bischof concluded. "Three years of imatinib following resection results in improved overall and recurrence-free survival compared with one year. Accurate risk stratification is essential to determine appropriate candidates for adjuvant imatinib."

Novartis Pharmaceuticals sponsored the study, employed two of the seven authors, provided consultancy fees to the Analysis Group, and preapproved the comments Dr. Guerin provided for this story.

SOURCE: http://bit.ly/1IgFNZm and http://bit.ly/1LZGoWH

JAMA Oncol 2015.