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THYROID CANCER
Obtaining molecular markers on thyroid biopsies prior to surgery may affect initial surgery and intensity of postoperative follow-up
BACKGROUND
Thyroid nodules are very common. When a biopsy is indicated for a patient with a thyroid nodule, the results are evaluated according to the risk of cancer (called the “Bethesda system”). Low risk patients (Bethesda 2) are often just monitored. For Bethesda 3 and 4 thyroid nodules, molecular marker testing is recommended and has led to increased accuracy for diagnosing thyroid cancers, allowing for more individualized treatment plans. Since the risk for cancer in Bethesda 5 and 6 nodules is greater than 50%, molecular marker testing is usually not done as most often patients are recommended to proceed to surgery. The surgery may be removal of the lobe containing the cancer (lobectomy) or removal of the whole thyroid (total thyroidectomy). After surgery, radioactive iodine therapy may be recommended. However, even in these cancers, some can be aggressive and others may be slow growing, progressing slowly and not posing an immediate threat.
Molecular marker testing can identify high risk thyroid cancers with increased likelihood of aggressive features, cancer recurrence after initial therapy, and spread outside of the thyroid. This study was performed to see if molecular marker testing for Bethesda 5 and 6 nodules could aid in prediction of the aggressiveness of the thyroid cancer and even help to determine the planned management.
THE FULL ARTICLE TITLE
Schumm MA et al 2023 Prognostic value of preoperative molecular testing and implications for initial surgical management in thyroid nodules harboring suspected (Bethesda V) or known (Bethesda VI) papillary thyroid cancer. JAMA Otolaryngol Head Neck Surg 149:735– 742. PMID: 37382944.
SUMMARY OF THE STUDY
This is a study of patients from a single institution who had Bethesda 5 or 6 thyroid nodules and thyroid cancer confirmed after surgery. They were classified into risk of cancer recurrence based on 2014 American Thyroid Association guidelines. Samples of the nodules were analyzed using ThyroSeq molecular testing and stratified into Cancer Risk Classifier molecular risk groups, which are based on the probability of cancer aggressiveness. These groups include (i) negative (no detectable genetic alteration); (ii) low-risk (RAS and RAS-like alterations); (iii) intermediate risk (BRAF V600E or other BRAF-like alterations); and (iv) high risk (combination BRAF/RAS plus TERT or other high-risk alterations). Molecular testing results were then correlated with available clinical follow-up data. Outcomes included cancer persistence or recurrence, spread of the cancer outside of the thyroid and cancer recurrence-free survival.
There were 105 patients identified, all of whom had papillary thyroid cancer and were followed for an average of 3.8 years. The average age was 44 and 68% were female. Molecular markers were identified in 100 (95%) of these samples, of which 6 (6%) were low disease risk, 88 (88%) intermediate disease risk, and 6 (6%) high disease risk.
When no molecular markers were identified (n=5) or there was low risk cancer (n=6), there was no recurrence or spread of the cancer outside of the thyroid identified in follow up. In the 88 patients with intermediate disease risk, 6 (7%) experienced recurrence of the cancer, including 1 patient who also developed spread of the cancer outside of the thyroid. Those with high disease risk (n=6), all of whom demonstrated BRAF V600E plus TERT mutations, underwent total thyroidectomy followed by radioactive iodine therapy. Of these 6 highdisease- risk patients, 4 (67%) developed recurrence of the cancer, 3 of whom also developed spread of the cancer outside of the thyroid.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that when patients were found to have high risk molecular markers, they were more likely to have persistent or recurrent cancer and spread of the cancer outside of the thyroid than patients with intermediate or low risk molecular markers. In contrast, 100% of those with low risk molecular markers had 36-month cancer recurrence-free survival. This study suggests the possibility of considering less surgery or avoiding radioactive iodine therapy in patients with low and intermediate risk molecular markers despite having Betheseda 5 or 6 nodules.
— Marjorie Safran, MD
ATA RESOURCES
Thyroid Cancer (Papillary and Follicular): https://www.thyroid.org/thyroid-cancer/
ABBREVIATIONS & DEFINITIONS
Thyroid biopsy: a simple procedure that is done in the doctor’s office to determine if a thyroid nodule is benign (non-cancerous) or cancer. The doctor uses a very thin needle to withdraw cells from the thyroid nodule. Patients usually return home or to work after the biopsy without any ill effects.
Molecular markers: genes and microRNAs that are expressed in benign or cancerous cells. Molecular markers can be used in thyroid biopsy specimens to either to diagnose cancer or to determine that the nodule is benign. The two most common molecular marker tests are the Afirma™ Gene Expression Classifier and Thyroseq™
Genes: a molecular unit of heredity of a living organism. Living beings depend on genes, as they code for all proteins and RNA chains that have functions in a cell. Genes hold the information to build and maintain an organism’s cells and pass genetic traits to offspring.
Mutation: A permanent change in one of the genes.
Cancer-associated genes: these are genes that are normally expressed in cells. Cancer cells frequently have mutations in these genes. It is unclear whether mutations in these genes cause the cancer or are just associated with the cancer cells. The cancer-associated genes important in thyroid cancer are BRAF, RET/PTC, TERT and RAS.
BRAF gene: this is gene that codes for a protein that is involved in a signaling pathway and is important for cell growth. Mutations in the BRAF gene in adults appear to cause cancer.
microRNA: a short RNA molecule that has specific actions within a cell to affect the expression of certain genes.
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