HONOLULU – A DNA-based molecular diagnostic test that stratifies pancreatic cysts for their malignant potential better than current alternatives can help guide management, according to two sets of corroborating data presented at the annual meeting of the American College of Gastroenterology.
The test was associated with a high degree of accuracy for identifying those pancreatic cysts with a high as well as those with a low potential for malignant transformation, according to Dr. David E. Loren, codirector, pancreaticobiliary section, Thomas Jefferson University, Philadelphia.
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“This test can be recommended across the board to patients with a pancreatic cyst. The exception would be those with a positive cytology for malignancy in which no further diagnostic study is needed,” said Dr. Loren.
The proprietary test, marketed under the name PancraGEN (Interpace Diagnostics), uses genetic and molecular information, such as oncogene mutations and loss of heterozygosity (LOH) markers, to stratify pancreatic cysts as high risk on the basis of malignant transformation potential or low risk on the basis of characteristics predicting a benign course. It is commercially available and has been used in more than 14,000 patients worldwide, according to Dr. Loren.
In the first of two studies presented at ACG 2015, the performance of the diagnostic test was compared to AGA criteria for managing pancreatic cysts, which were published earlier this year (Gastroenterology 2015;148:819-22). Using registry data with known outcomes, researchers compared the performance of the AGA criteria and the PancraGEN test in 417 patients.
The AGA criteria, which require assessment of cytological atypia and endoscopic ultrasound imaging features, were falsely negative in 57% of cases and falsely positive in 4%, producing a positive predictive value of 59% and a negative predictive value of 93%. Of the 27 malignancies missed by the AGA criteria, the PancraGEN test identified 21. As a result, it generated far greater sensitivity (87% vs. 43%; P less than .0001) even though the specificity of the PancraGEN test and the AGA criteria were similar (92% vs. 96%, respectively).
“The DNA-based approach helped identify false-negative cases otherwise missed by AGA-recommended imaging and cytology,” Dr. Loren confirmed.
In a second study using the same registry data, the goal was to determine whether the DNA-based diagnostic test would provide more accurate management decisions. In this study, the DNA-based diagnostic test was compared to the International Consensus Guidelines (ICG), which were most recently updated in 2012 (Pancreatology 2012;12:183-197). The study evaluated outcomes in the context of recommendations by the ICG as well as the risk status established with the PancraGEN test.
In cysts recommended for surveillance by ICG but identified as high-risk by PancraGEN testing, 57% had malignant outcomes. In cysts recommended for Surgery by ICG guidelines but identified as low-risk by PancraGEN test, 99% had a benign outcome.
Whether compared to AGA or ICG criteria, the DNA-based test is more accurate for detecting malignant potential “without drastically overdiagnosing malignancy in patients with benign lesions,” said Dr. Loren, who said the second study confirmed its utility “in real-life management decisions.”
Cost efficacy data were not presented at the ACG meeting, but Dr. Loren said that models predict cost savings from PancraGEN testing because of more appropriate care, particularly a reduction in unnecessary surgeries. Although it is also theoretically possible that a reduction in false-negative diagnoses could lead to a mortality benefit through earlier treatment of lesions with a high likelihood of malignant transformation, Dr. Loren cautioned that this advantage would be difficult to show without extended follow-up because of the slow growth of many tumors.
It is estimated that about 120,000 pancreatic cysts are identified annually. On cytology, results are often ambiguous, complicating the decision to incur the risks and costs of surgery relative to a watch-and-wait approach. A more precise test has the potential both to avoid unnecessary surgeries and to ensure that those at high risk are treated appropriately. Overall, Dr. Loren said he believes that the PancraGEN test will improve care in this population.
“We think this is a better approach relative to current alternatives,” he asserted.
Dr. Loren received research support from Interpace Diagnostics