Changes in the Management of Thyroid Cancer

Changes are stirring in the management of thyroid cancers, from molecular testing to surveillance in select cases, and from nerve monitoring to the choice between total thyroidectomy over hemi-thyroidectomy for certain tumors. An expert panel reviewed the main points in a session at the Triological Society Combined Sections Meeting, held in Coronado, Calif., January 24–26, 2019.

Robert Witt, MD, professor of otolaryngology–head and neck surgery at Thomas Jefferson University in Philadelphia, said molecular tests are becoming increasingly important in the diagnosis and exclusion of thyroid cancer. “We are, I believe, at the beginning of a renaissance in the management of thyroid disease,” he said. “And I think it’s spearheaded by molecular testing.”

There are four main commercial testing options: the Genetic Sequencing Classifier; ThyroSeqv3; ThyGenX & ThyraMIR; and RosettaGX Reveal. The value of the testing on indeterminate thyroid nodules (Bethesda Grade 3 or 4) stems from their ability either to improve accuracy of ruling in thyroid cancer, with positive predictive values that can cut down on the number of completion thyroidectomies, or to rule out thyroid cancer, with negative predictive values that can reduce unnecessary surgery on indeterminate thyroid nodules that would ultimately be found to be benign if they underwent operation.

Positive predictive values (PPV) with the available tests stand at 47% to 82%. Negative predictive values (NPV) are much better, ranging from 91% to 99%. “This is the real stronghold of molecular testing today,” Dr. Witt said, referring to NPV. “I think the positive predictive values are a little bit wanting.” But he added that a lot of nodules labeled suspicious, but not certain for cancer by these tests, and treated with diagnostic lobectomy, will be low-grade, such as follicular variant papillary thyroid cancer, and many don’t require completion thyroidectomy.

“I’m expecting in the next year—or two or three—that the PPV on all of these tests is going to bump up with advancements in mutation identifications and microRNA analysis,” he said.

Ultimately, on the question of whether molecular testing for indeterminate thyroid nodules improves specificity analysis and positive predictive value, the answer, Dr. Witt said, is “maybe.” For BRAF or RET/PTC mutations, the answer is yes, but discovery of other mutations might not eliminate completion thyroidectomy if a diagnostic lobectomy was performed. But, he added, completion thyroidectomy, depending on clinical evaluation and ultrasound, is not mandated by American Thyroid Association guidelines for differentiated thyroid cancers smaller than 4 cm.