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Matrone et al. J Cancer Metastasis Treat 2021;7:23 Journal of Cancer
DOI: 10.20517/2394-4722.2021.47
Metastasis and Treatment

Review Open Access

Systemic treatment of advanced, metastatic,
medullary thyroid carcinoma

Antonio Matrone, Carla Gambale, Alessandro Prete, Virginia Cappagli, Loredana Lorusso, Valeria Bottici,
Rossella Elisei
Department of Clinical and Experimental Medicine, Endocrine Unit, University Hospital of Pisa, Pisa 56124, Italy.
Correspondence to: Dr. Antonio Matrone, Department of Clinical and Experimental Medicine, Endocrine Unit, University
Hospital of Pisa, Via Paradisa 2, Pisa 56124, Italy. E-mail: anto.matrone@yahoo.com

How to cite this article: Matrone A, Gambale C, Prete A, Cappagli V, Lorusso L, Bottici V, Elisei R. Systemic treatment of
advanced, metastatic, medullary thyroid carcinoma. J Cancer Metastasis Treat 2021;7:23. https://dx.doi.org/10.20517/2394-
4722.2021.47

Received: 26 Feb 2021 First Decision: 31 Mar 2021 Revised: 2 Apr 2021 Accepted: 13 Apr 2021 Published: 26 Apr 2021

Academic Editor: Jerome M. Hershman Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
Medullary thyroid carcinoma (MTC) is a rare endocrine tumor, which arises from thyroid parafollicular C cells.
Through its ability to metastasize by blood and lymphatic vessels, it can show a more aggressive clinical behavior
than differentiated thyroid cancers. Mutation of RET gene is the main molecular alteration involved in MTC origin.
In the case of germline RET mutation, MTC can be inherited in an autosomal dominant way and show three
different phenotypes: familial medullary thyroid carcinoma and multiple endocrine neoplasia types IIA and IIB. In
addition, in sporadic cases, somatic RET mutation remains the key molecular alteration in most of cases. Total
thyroidectomy with prophylactic or therapeutic central compartment lymph nodes dissection is the surgical
treatment of choice. Further surgical treatments and local therapies should be used in the case of single or few local
or distant metastasis. However, in cases with large metastatic spread of the disease, particularly in those with
significant tumor progression, additional systemic treatments are needed. In this review, we discuss the key points
of systemic treatment in advanced, metastatic MTC. We provide an update on the main aspects (from biological
rationale to clinical experience) of each treatment, focusing our attention on the drugs used in clinical practice in
the last years. Finally, we give insights about the emerging treatments from highly selective RET inhibitors to new
radionuclide therapy.

Keywords: Medullary thyroid carcinoma, tyrosine kinase inhibitors, targeted therapy, immunotherapy, radionuclide
therapy, RET selective inhibitors

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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