Medullary thyroid cancer: features of medical and tactical approaches and postoperative management of patients

Abstract

An analysis of the current state of the problem of treatment of medullary thyroid cancer (МТС), which is offi cially recognized as an orphan disease, is presented. Medullary carcinomas (MC) are fundamentally diff erent from other thyroid neoplasms, namely: they arise as a result of malignancy of parafollicular cells; have a specifi c hormonal marker – calcitonin (CT); progress more aggressively with more frequent relapses and higher patient mortality; are more often multicentric; the therapeutic arsenal against MС is limited. МТС is associated with a germline mutation (causes the development of MС, which is familial) or a somatic mutation (responsible for sporadic MC) in the RET proto-oncogene. Hereditary forms of thyroid MC are represented by three clinical variants: MC as part of multiple endocrine neoplasia syndromes – MEN-2A and MEN-2B – and familial MC, not burdened by other endocrine disorders. The prognosis of thyroid MC is disappointing for patients with distant metastases who are diagnosed at the preoperative stage. Detection of metastases is often diffi cult, because the ultrasound or cytological picture of the disease is atypical, and metastases are often microscopic and diffi cult or even impossible to identify. The clinical behavior of MC is sometimes unusual, as metastatic disease can remain stable for decades, undergoing sudden, unexpected, and rapid progression. The peculiarities of MTC, to some extent, are refl ected in the tactics of its treatment. Modern guidelines provide for the need for an extremely complete assessment of the nature of regional metastatic lesions. Extensive thorough surgery is the only treatment option for localized MK, and a total thyroidectomy,
supplemented in all cases by a central dissection of the lymph nodes of the neck, is recognized as a minimal amount of surgical intervention. The necessity and extent of prophylactic lateral lymphatic dissection is widely debated. The size of the tumor, the presence, localization and number of metastases detected at the preoperative stage, the basal or stimulated content of CT in the blood of patients are discussed as factors that determine the volume of surgery. The terms and scope of surgery for carriers of the mutant RET gene and their family members depend on the type of mutation, the age of the patients and the type of MEN-2 syndrome. In the postoperative period, in order to assess the function of the parathyroid glands and the risk of hypoparathyroidism, the level of ionized calcium in the blood serum is constantly monitored. Patients need lifelong thyroid hormone analogues, vitamin D and calcium preparations. The state of the disease after surgical treatment is classifi ed into 3 groups: excellent response to treatment or curability, incomplete biochemical response, negative response. Approaches to the postoperative treatment of patients depend on various clinical factors, which include: the presence of symptoms, signifi cant structural progression, localization of metastases, their volume, the level of CT in the blood and its doubling time, the severity of the disease. Management options for patients with residual unresectable disease include close observation, external beam radiation therapy, local treatments such as embolization, radiofrequency, chemoor cryoablation, and systemic treatment (chemotherapy, use of immune checkpoint inhibitors, etc.). The features of modern targeted therapy with the use of multityrosine kinase inhibitors (vandetanib, cabozantinib) and specifi c RET inhibitors (selpercatinib and pralcetinib), which are already offi cially approved for the treatment of MTC, are considered. Questions regarding the targeted treatment MTC, which are still open today, have been identified.