Reviewing Treatment Guidelines for Medullary Thyroid Carcinoma

The majority of physicians working in hospitals and clinics around the world are not directly involved in medical research and the development of treatment guidelines. Instead, we have an instinctive trust in the medical and governmental institutions that are responsible for publishing updated treatment protocols and guidelines according to the best and latest research.

Under normal circumstances, changes in treatment guidelines are not drastic and only occur once every few years. For example, the treatment guidelines for diabetes have remained virtually unchanged for years, despite the growing number of novel therapies under investigation. In fluid circumstances, such as in the case of the coronavirus disease 2019 (COVID-19) pandemic, the ink has barely dried before adjustments are made to treatment guidelines while keeping up with the emergence of new research.

In the case of medullary thyroid carcinoma (MTC), the last time the American Thyroid Association (ATA) updated its treatment guidelines was in 2015. However, a few other organizations have provided updated treatment guidelines since then, including the European Association for Medical Oncology (ESMO), Japanese Association of Endocrine Surgeons (JAES), and National Comprehensive Cancer Network (NCCN), which published its latest guidelines in 2021.

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Two Korean researchers, Mijin Kim and Bo Hyun Kim, recently conducted a literature review of the various treatment guidelines for MTC and summarized them in an article published in Endocrinology and Metabolism. We will take a closer look at their findings in this article.

Surgical Guidelines

In Korea, MTC accounts for 0.6% of all thyroid cancers; in the United States, this figure is between 1% to 2%. Based on current evidence, the authors concluded that “complete surgical resection of the thyroid tumor and any locoregional metastases is the only curative option for locoregional MTC.” Early diagnosis and detection of MTC are crucial to improving prognosis.

Total thyroidectomy (as opposed to subtotal thyroidectomy or hemithyroidectomy) has gained consensus as being the best form of surgical treatment, given that bilateral or multifocal disease occurs in nearly all patients with inherited MTC; in sporadic MTC, this figure drops to 10%.

When total thyroidectomy is performed, involved lymph node compartments are dissected as a standard approach for both inherited and sporadic MTC. This surgical approach preserves the functions of swallowing, speech, and the parathyroid gland, which are important for the postoperative quality of life of patients.

Read more about MTC epidemiology

More controversial is the performance of lateral neck dissection in patients lacking evidence of lymph node metastasis upon preoperative ultrasound scans. This is because studies show that an aggressive approach to prophylactic lateral neck dissection can result in postoperative mortality without evident survival benefits.

The ATA takes a neutral stance on the issue, advocating neither for nor against prophylactic lateral neck dissection based on serum calcitonin levels. When there is intraoperative evidence of central lymph node involvement, ipsilateral neck dissection is still usually performed.

Both the ATA and ESMO agree that contralateral neck dissection should be considered in the event that the ipsilateral lateral neck compartment is positive but the contralateral neck compartment is negative on preoperative imaging and when basal serum calcitonin levels are greater than 200 pg/mL. If preoperative calcitonin levels are below 20 pg/mL, prophylactic central neck dissection is not recommended in small intrathyroidal MTC because there is no risk of lymph node metastasis.

Every time surgical intervention is needed, patients should be adequately counseled on the risks involved. The researchers wrote, “It is very important that individualized surgical decisions should be made according to life expectancy, underlying comorbidities, and the patient’s wishes.”

Peptide Receptor Radionuclide Therapy

Aside from surgical intervention, are there any noteworthy noninvasive treatments that are currently in use or under investigation? Grossrubatscher and colleagues investigated the potential role of peptide receptor radionuclide therapy (PRRT) in treating advanced/metastatic MTC and discovered that it could be a viable therapeutic option.

Their literature review referred to a study in which PRRT with somatostatin analogues radiolabeled with 90 yttrium and 177 lutetium yielded a significant disease control rate in 62.4% of MTC cases, most of which were already in progression at baseline. Importantly, this result was coupled with low toxicity.

In patients who were responsive to PRRT, the researchers found that it had a stabilizing effect on the disease. Grossrubatscher et al wrote, “In particular, one study demonstrated longer survival in patients with radiological disease control, and two studies demonstrated longer survival in patients with a biochemical response, evaluated through calcitonin assessment, which, in MTC, can indicate tumor recurrence or progression and indicate a treatment response with good sensitivity.”

Read more about MTC etiology

The limitations of this literature review on the efficacy of PRRT were the small sizes of most case series analyzed and the highly heterogeneous and sometimes incomplete data collected on factors such as treatment schedule, response evaluation, and follow-up. However, this literature review sufficiently demonstrates that nonsurgical approaches to treating MTC show promise.

Research into PRRT in patients with MTC is still ongoing, so we will learn about just how far this treatment can go in the years ahead. Grossrubatscher et al concluded, “This lesser-known but promising therapy is expected to establish a new and efficient strategy for the treatment of MTC, which is still a challenging entity.”