Clinical Thyroidology® for the Public
Summaries for the Public from recent articles in Clinical Thyroidology
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THYROID CANCER
Can my biopsy results predict the likelihood of my thyroid cancer coming back?
BACKGROUND
Although most thyroid cancers are low-risk and have an excellent prognosis, there can be very different types of thyroid cancers that may be more aggressive and harder to treat. The initial treatment for thyroid cancer is usually surgery, and often this is the only treatment needed. For patients with more advanced cancer, radioactive iodine therapy serves as a “magic bullet” to seek out and destroy thyroid cancer cells. The treatment plan for thyroid cancer is usually based on cancer staging systems. While some cancer staging systems focus on risk of dying, the American Thyroid Association focuses more on risk of recurrence of the cancer, since most thyroid cancer patients do not die of the cancer. Most cancer staging systems require information that can only be obtained while the surgery is being performed or after the surgical specimen is analyzed. However, even these systems have limitations. For example, a thyroid cancer that is contained within one thyroid lobe and not involving any other neck structures is considered low-risk of recurrence but can still recur in 5-20% of cases.
The management of thyroid cancer is becoming more conservative, with more frequent recommendations of removing only the thyroid lobe containing the cancer or even following the cancer with ultrasound without an operation (active surveillance). Until now, the molecular marker information that is obtained from the biopsy mainly helped us know the likelihood cancer was present and what type of cancer it was. Ideally, we could use the molecular marker information to know the risk of recurrence of cancer to determine the ideal extent of surgery, usefulness of radioactive iodine therapy, and appropriate frequency of follow up of the cancer. This information might help the patient know whether to pursue active surveillance, lobectomy, or total thyroidectomy.
The goal of this study is to see if the molecular marker analysis obtained through a biopsy of the nodule before the surgery helped predict the risk of thyroid cancer recurrence and guide the care team for the extent of surgery.
THE FULL ARTICLE TITLE
Bauzon J et al. Validation of molecular profiling to preoperatively predict aggressive pathologic features in differentiated thyroid cancer. Surgery 2026;189:109698
SUMMARY OF THE STUDY
This study looked at the results from 2,652 patients at a single hospital. In this group, there were 2,980 nodules biopsied. A total of 445 thyroid nodules resulted in biopsy results that were indeterminate or cancer. In these cases, molecular analysis was performed using the Genomic Sequencing Classifier (GSC) molecular test by Afirma™ and analyzed using the Veracyte Genomic Resource for Intelligent Discovery (GRID) tool. These 445 nodules were analyzed with Afirma for molecular genetics, and a risk of recurrence of the thyroid cancer was determined after the surgery was performed. The thyroid cancer cell expression of a sodium iodine (NIS) transporter is an important sign that the cancer will likely respond better to radioactive iodine treatment. The cancer invasiveness and the presence or absence of lymph node involvement were determined from the surgical pathology.
Of the 445 nodules, 366 (82%) were classified as low risk, 57 (13%) were intermediate risk, and 22 (5%) were high risk of recurrence. The expression of the sodium-iodine transporter decreased risk of recurrence, and the degree of invasiveness of the cancer increased risk of recurrence. The molecular genetics Afirma testing was effective at predicting whether a cancer would be low or intermediate/ high risk of recurrence.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that molecular markers that are identified on thyroid nodule biopsy specimens performed prior to surgery can help tailor the treatment for the patient’s thyroid cancer. The biopsy molecular marker analysis helped predict the risk of thyroid cancer recurrence and, thus, guide the care team for extent of surgery. While further studies are needed to confirm these results, this study provides more information to help the patient and doctor to determine the best treatment options for the patients’ thyroid cancer.
— Pinar Smith, MD
ATA RESOURCES
Thyroid Nodules: https://www.thyroid.org/thyroid-nodules/
Thyroid Cancer (Papillary and Follicular): https://www.thyroid.org/thyroid-cancer/
ABBREVIATIONS & DEFINITIONS
Thyroid nodule: an abnormal growth of thyroid cells that forms a lump within the thyroid. While most thyroid nodules are non-cancerous (Benign), ~5% are cancerous.
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.
Indeterminate thyroid biopsy: this happens a few atypical cells are seen but not enough to be abnormal (atypia of unknown significance (AUS) or follicular lesion of unknown significance (FLUS)) or when the diagnosis is a follicular or hurthle cell lesion. Follicular and hurthle cells are normal cells found in the thyroid. Current analysis of thyroid biopsy results cannot differentiate between follicular or hurthle cell cancer from noncancerous adenomas. This occurs in 15-20% of biopsies and often results in the need for surgery to remove the nodule.
Thyroid cancer: the most common type of thyroid cancer, includes papillary, follicular and oncocytic thyroid cancer.
Cancer recurrence: this occurs when the cancer comes back after an initial treatment that was successful in destroying all detectable cancer at some point.
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.
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.
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™
Thyroidectomy: surgery to remove the entire thyroid gland. When the entire thyroid is removed it is termed a total thyroidectomy. When less is removed, such as in removal of a lobe, it is termed a partial thyroidectomy or lobectomy.
Radioactive iodine (RAI): this plays a valuable role in diagnosing and treating thyroid problems since it is taken up only by the thyroid gland. I-131 is the destructive form used to destroy thyroid tissue in the treatment of thyroid cancer and with an overactive thyroid. I-123 is the nondestructive form that does not damage the thyroid and is used in scans to take pictures of the thyroid (Thyroid Scan) or to take pictures of the whole body to look for thyroid cancer (Whole Body Scan).
Active Surveillance: following a small, low-risk thyroid cancer with ultrasound and deferring surgery until the cancer grows significantly
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