Is peptide receptor radionuclide therapy still a promising option for medullary thyroid carcinoma?

Medullary thyroid carcinoma (MTC) is a rare cancer that originates from germline RET proto-oncogene mutations in all hereditary forms and from somatic RET mutations in most sporadic cases. Currently, highly selective RET inhibitors have been approved for clinical use in patients with RET mutations with persistent, recurrent or metastatic disease. This therapy has proven efficacy, low toxicity, and a limited impact on patients' quality of life. However, for recurrent or metastatic RET-negative disease, few systemic therapies are available. Multikinase inhibitors are used; however, tumour cells frequently develop resistance mechanisms, or treatment must be discontinued due to the high incidence of side effects. In this context, peptide receptor radionuclide therapy (PRRT) may be a treatment option, but its clinical utility remains under investigation. The aim of this review is to evaluate the evidence of PRRT in MTC and discuss its limitations in the RET inhibitor era.