Table 1.

Recommendations of the American Thyroid Association (ATA) Guidelines (2015), Italian Consensus (2018), and National Comprehensive Cancer Network (NCCN) (2019) about the management of radioiodine-refractory locally advanced/metastatic differentiated thyroid cancer (DTC) patients.

Radioiodine-refractory locally advanced/metastatic DTC
	Active surveillance	Locoregional treatments	Systemic treatments
ATA 2015	Serial radiographic imaging (every 3–12 months) in patients with asymptomatic, stable, or minimally progressive disease, not likely to develop rapidly progressive, clinically significant complications. TSH-suppressive thyroid hormone therapy to be continued.	In case of symptoms and risk of local complications before systemic treatment (or during systemic therapy in case of progression of a single lesion): surgery, external beam radiotherapy (EBRT), percutaneous approach (i.e., radiofrequency, laser ablation, ethanol injection, cryoablation, cementoplasty) in selected cases.	Approved kinase inhibitor (KI; i.e., lenvatinib, sorafenib) in rapidly progressive, symptomatic, and/or imminently threatening disease not otherwise controlled using other approaches. Second-line KI therapy in case of progression or prohibitive adverse effects on first-line treatment (ideally within the context of clinical trials). Few data and disappointing results about conventional chemotherapy; to be considered after failure of KI therapy. Bisphosphonates (especially zoledronic acid every 3 months) or denosumab in case of diffuse and/or symptomatic bone metastases.
Italian Consensus 2018	Cross-sectional imaging at regular intervals (every 3–12 months) in case of stable disease without symptoms, with a slow progression during the follow-up and without lesions at risk of life. TSH-suppressive thyroid hormone therapy to be continued.	Strongly suggested in case of progression related to a single lesion treatable with a local and selective approach: surgery, EBRT, other local procedures (i.e., thermoablation, ethanol injection, chemoembolization).	Approved KI (i.e., sorafenib, lenvatinib) for rapidly progressive, significantly symptomatic, and/or with life threatening lesions not suitable for local therapies. In case of progressive disease during KI therapy, indication to another KI based on evidence of high probability of efficacy. Traditional chemotherapy only in case of failure or contraindication of KI.
NCCN 2019	In case of non-progressive and indolent disease, distant from critical structures. TSH-suppressive thyroid hormone therapy to be continued.	To be considered in case of progressive and/or symptomatic disease if feasible, depending of the site, and the number of tumoral foci: surgery, EBRT, other interventional procedures (i.e., ethanol ablation, cryoablation, radiofrequency, embolization) in selected patients.	Lenvatinib (preferred) or Sorafenib for progressive and/or symptomatic disease. Other commercially available KI to be considered if clinical trials not available or appropriate. Minimal efficacy of cytotoxic chemotherapy. Intravenous bisphosphonates or denosumab if bone metastases.