Meta-review Finds That RAS PPV Is Lower Than Previously Reported


Dr. Mark Lupo presented a systematic review of the positive predictive value of RAS mutations at the 25th Annual Meeting of the American Association of Clinical Endocrinologists.


Methods: The literature review in PubMed was conducted through 12/1/2015. Studies were included that reported RAS mutational status and surgical follow-up for cytologically indeterminate nodules. Meta-analyses were constructed calculating the sensitivity, specificity, PPV, and NPV of RAS mutations in cytologically indeterminate nodules.

Results: In the review of 19 studies, RAS was found to have a PPV of 67.7%, in contrast to the 80% that had been quoted recently in the literature. Further analysis revealed that the PPV in the 15 un-blinded studies was 68% compared to the 60% in the 4 studies with blinded pathology review. Furthermore, there was a statistically significant difference in the reported RAS PPV between studies performed at UPMC compared to non-UPMC studies (84% vs 51.5%, p During the presentation, Dr. Lupo presented his own practice’s experience with 18 RAS positive patients from the past 4 years. 15 cytologically indeterminate, RAS positive nodules underwent surgical resection, and 10 (67%) were histologically benign (PPV = 33%).

Summary: “Physicians should be cautious that pathologists are more likely to label a nodule as malignant when they know a RAS mutation is present. This bias may result in cancer over-diagnosis and over-treatment.”

“RAS alone as a mutation in a [thyroid] nodule probably does not have the positive predictive value we thought, and even if they’re cancerous those nodules tend to be fairly indolent”

“We have to take the clinical information together to make the [treatment] decision. RAS alone doesn’t tell the whole story.”


Visit (page 286) to read the 2016 AACE abstract

Visit to read the Medscape Medical News article reporting on the AACE 2016 oral presentation

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