Unresolved issues, dilemmas and points of interest in thyroid cancer: a current perspective

Thyroid cancer (TC) is the commonest endocrine malignancy. In the overwhelming majority of cases, thyroid carcinomas are well-differentiated malignancies that respond favorably to treatment; however, this outcome cannot be absolutely guaranteed. The absence of large prospective randomized clinical trials in TC-due to its low incidence and protracted clinical course in cases with persistent/recurrent metastatic disease-results in considerable debates regarding the optimal treatment and follow-up regimens in this malignancy. Some of these debates originated several decades ago, yet are still ongoing despite interim advancements in other domains of oncology. Here we discuss what we believe are the issues of major controversy in TC; these are mentioned in the following non-exhaustive list: (i) the optimal management of solitary and multiple thyroid nodules; (ii) the role of basal calcitonin measurements in the diagnostic investigation of nodular thyroid disease; (iii) the extent of the initial operation after establishment of the diagnosis of TC; (iv) the intensity and frequency of radioactive iodine (RAI; (131)I) therapies (especially in patients with persistent/recurrent metastatic disease); (v) the degree and duration of long-term thyroid hormone suppression therapy (THST) required for optimal outcomes in TC patients; (vi) the optimal management of patients with RAI-refractory disease or other "high-risk" clinicopathologic features; and, finally, (vii) the optimal algorithm for lifelong follow-up of TC patients after their initial treatment. We present elements of the above controversies as pertinent to the various types of TC. We have opted for breadth rather than depth of commentary, at the same time providing the reader with extended up-to-date bibliography.