Molecular 'Theranostics' Could Guide Treatment in Thyroid Cancer

Nancy A. Melville

August 18, 2021

A new joint statement by the American Thyroid Association (ATA), European Thyroid Association, and Society of Nuclear Medicine and Molecular Imaging tackles the rapidly evolving role of molecular markers in the diagnosis and treatment of thyroid cancer with radioactive iodine (RAI), supporting their increased implementation, particularly for risk stratification. 

The statement was issued as ever more data on molecular markers help launch a "new paradigm" in the approach to thyroid cancer, while driving ongoing debate over how they will feed into the use of RAI, first author Seza A. Gulec, MD, of the Herbert Wertheim College of Medicine, Florida International University, in Miami, told Medscape Medical News.

"The controversy over the appropriate use of RAI in thyroid cancer goes back 70 years, as we've been long using it based on the assumption that the majority of high-risk tumors respond to RAI," he explained. 

"But the new paradigm calls for identifying, through molecular analysis, the cancers that have the ability to respond to RAI and/or those that could have the response to RAI enhanced through pretreatment."

In the statement, published in Thyroid, the working group for the three societies describes their agreement on key issues in three broad areas of RAI use: RAI in perioperative risk stratification, the role of RAI imaging in initial staging, and the need to refine understanding of markers of response to RAI therapy.

Avoid Unnecessary Treatment 

The working group underscores the value of the traditional risk stratification and staging models for thyroid cancer — the American Joint Committee on Cancer eighth edition staging rules and ATA risk stratification system — in the immediate perioperative period, which is well-established.

The group supports the inclusion of secondary prognostic factors, specifically molecular markers, in risk stratification in the perioperative period, citing their therapeutic and diagnostic (or theranostic) value in improving individualized treatment decisions.

Molecular theranostics comprise molecular cytology, molecular pathology, and molecular imaging.

"Traditional risk stratification systems can be further refined by...judicious incorporation of molecular theranostics in the primary framework to guide initial patient management decisions," the authors write.

Gulec said the inclusion of molecular analysis in risk stratification in particular offers the potential to avoid unnecessary treatment in people who can be identified as likely nonresponders.

"The bottom line is that we need to know more about the cancer before we make decisions on how to tackle it," he told Medscape Medical News.

"For the thyroid cancer to respond to RAI, it has to have an intact system to handle the treatment, and the fact is that most high-risk patients have a molecular profile that does not allow them to respond to RAI or to benefit from total thyroidectomy," Gulec explained.

However, the ability to perform a complete genomic analysis with advanced molecular sequencing and identify those patients is radically changing things, he concluded.

Gulec has  rep­orted no relevant financial relationships.

Thyroid. Published online July 8, 2021. Full text

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