April 23, 2021
From 1975 to 2009, microscopic papillary thyroid carcinoma (mPTC) incidence skyrocketed 49%; yet, mortality remained stable. Imaging advances and increased screening rates led to elevated incidental low-risk mPTC findings.
mPTC 发病率增加
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"The marked increase in thyroid cancer is due to the papillary type," says Marius N. Stan, M.D., an endocrinologist at Mayo Clinic in Rochester, Minnesota. "Medical centers have been doing much more imaging in the last two decades. Basically, CT of chest, neck or head; carotid ultrasound; spine MRI; and PET scans are all studies likely to include some thyroid images. Once you open this Pandora's box, you will likely find small thyroid nodules."
Dr. Stan says thyroidologists refer to nodules discovered by chance when imaging other areas of the body as incidentalomas. These nodules are small and mostly not clinically significant; however, 5% are cancerous. Physicians assess these nodules' risk only through dedicated thyroid imaging and biopsy.
Previously, physicians discovered tiny cancerous nodules — 0.5 to 1 inch in size — only on palpation. Now, with more effective imaging, they can detect cancers measuring 0.2 inch. A thyroid cancer measuring 10 mm or less rarely presents significant problems, says Dr. Stan.
South Korea took a different tack than the U.S. and screened its asymptomatic general population for thyroid cancer, according to an article in a November 2016 issue of BMJ. The country's new cancer incidence increased over 10 times due to higher imaging volumes.
Beyond increased imaging with greater precision, environmental factors also play a role in elevated mPTCs, though not yet well defined. Thyroidologists are investigating these factors in the development of smaller and larger thyroid cancer findings.
Though mortality is low, higher thyroid cancer incidence has led to increased surgery and radioactive ablation therapy with associated side effects and complications, raising questions about appropriate treatment plans.
When watchful waiting is warranted
Dr. Stan calls for a balance between measured observation and treatment of thyroid cancers and says differentiation between high- and low-risk mPTCs is crucial, especially considering a Japanese study where investigators found results differed little over time between patients who experienced mPTC removal versus patients placed on active surveillance (AS).
According to the 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules or differentiated thyroid cancer, high-risk mPTC of ≤ 10 mm warrants surgery given these characteristics suggesting elevated risk:
- N+ or M+
- High-grade malignancy, per cytology specimen analysis
- Disease progression
- Tracheal invasion or recurrent laryngeal nerve injury indications
However, if the endocrinologist determines that a patient's mPTC is low risk, AS is appropriate, says Dr. Stan.
When treatment is selected: Standard intervention and RFA
Previously, endocrinologists considered surgical consultation warranted if patients refused AS or the physician observed tumor growth or nodal metastases, according to a publication by Dr. Ito and colleagues in the September 2020 issue of Annals of Thyroid. As ablative therapies emerged, delivering focused thermal energy to destroy mPTC — such as percutaneous ethanol ablation, laser ablation, radiofrequency ablation (RFA), microwave ablation or high-intensity focused ultrasound — the treating endocrinologist's options for patients expanded.
U.S. interventional radiologists initially used RFA, currently the most-used ablative therapy, for golf ball-sized lesions that affected swallowing and altered the patient's aesthetics. Researchers found these larger lesions decreased 50% to 80% in the first year post-treatment, prompting RFA use in smaller thyroid cancers.
RFA looks much like a needle biopsy and uses ultrasound-based energy to raise the local temperature in the thyroidal targeted area to 101 to 105 degrees C. It administers variable energy to each nodule, causing irreversible cell changes within a 3- to 5-mm region. Thrombosis occurs, followed by ischemia and fibrosis, and finally nodule shrinkage.
An interventional radiologist performs RFA while the patient is under general anesthesia, followed by two to three hours of observation. Nodule function and size dictate the total number of RFA sessions needed, with a two-session mean required per nodule, occurring one to two months apart.
Precise technique is key to RFA's success. The interventional radiologist places the needle through the isthmus into the nodule to minimize skin impact from the thermal energy. Needle tip placement is guided by ultrasound, and the ablation proceeds from distal to proximal aspect of the target nodule, according to findings published in a 2012 issue of International Journal of Endocrinology.
Benefits of RFA over surgery
RFA for mPTC offers many advantages compared with surgery, such as cost, targeted treatment, no scarring and reduced pain.
Cost
RFA cost is less than one-half of surgical thyroid lobe removal.
Targeted treatment
RFA is highly focused and treats only the cancer, sparing the thyroid and avoiding normal surrounding tissue damage when performed by an experienced interventional radiologist. Surgery entails removing half the thyroid, frequently leading to hypothyroidism and lifelong treatment.
No scarring
While visible scarring typically appears after surgical node removal, RFA avoids long-term scarring. Immediately after RFA, patients may experience minor discomfort and bruising, which becomes invisible after three to seven days.
Reduced pain
Virtually all patients tolerate any pain post-RFA with acetaminophen. Dr. Stan says only one patient he's seen has experienced pain past two to three days.
While he is not ready to call RFA curative for mPTC until long-term data is available, Dr. Stan says South Korean research published in a December 2020 issue of Thyroid reported excellent results at five years post-therapy.
Potential RFA side effects
Possible RFA side effects, which are rare, relate to high temperatures used near the mPTC. Dangers include:
- Vagus nerve irritation
- Recurrent laryngeal nerve damage
- Skin burns
Practitioner experience with RFA correlates with lower side effects, according to Dr. Stan, noting that Mayo Clinic interventional radiologists have performed RFA for cancerous and benign nodules for more than 15 years.
"The needle needs to be clearly visualized in the right spot before the radiologist applies any heat," says Dr. Stan. "If the placement is incorrect or the radiologist removes the needle too soon, it can cause damage."
Mayo Clinic RFA research and access
Dr. Stan and colleagues John J. Schmitz, M.D., and Anil N. Kurup, M.D., both with Radiology at Mayo Clinic in Rochester, Minnesota, recently completed treating an initial series of research subjects in a study started in 2020; they continue to monitor participants.
"Preliminary results look encouraging and are consistent with reports from South Korea, where radiologists have done RFA for many years," Dr. Stan says. "We are pioneers in the U.S. with RFA use and study, yet not in the world; we're learning from physicians' experience in South Korea, Italy and Denmark. We're trying to see how this therapy applies to the U.S. population. We're excited about RFA's possibilities."
Though enrollment is now closed for the study led by Drs. Stan and Matthew R. Callstrom, M.D., Ph.D., Radiology, physicians may refer patients with mPTCs to Mayo Clinic's campus in Rochester, Minnesota, for off-study treatment. Physicians may email Dr. Stan at stan.marius@mayo.edu to discuss RFA screening or other therapeutic options for diagnosed thyroid cancers.
Though insurance coverage is still at issue as the U.S. adopts RFA, Dr. Stan believes response is likely to be positive and he supports patients with explanatory letters to payers.
For more information
Park S, et al. Association between screening and the thyroid cancer "epidemic" in South Korea: Evidence from a nationwide study. BMJ. 2016;355:i5745.
Haugen BR, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules or differentiated thyroid cancer. Thyroid. 2016;26:1.
Ito Y, et al. Active surveillance for low-risk papillary microcarcinomas. Annals of Thyroid. 2020;5:22.
Shi JH, et al. Radiofrequency ablation of thyroid nodules: Basic principles and clinical application. International Journal of Endocrinology. 2012;2012:919650.
Cho SJ, et al. Long-term follow-up results of ultrasound-guided radiofrequency ablation for low-risk papillary thyroid microcarcinoma: More than 5-year follow-up for 84 tumors. Thyroid. 2020;30:1745.