Current Approach to Metastatic Differentiated Thyroid Cancer: Management of Organ-based Clinical Scenarios

This review aims to comprehensively summarize the current role of radioactive iodine (RAI) therapy, organ-based local approaches, and molecular targeted systemic therapies in metastatic differentiated thyroid cancer (DTC).The definition of radioiodine-refractory disease, the impact of tyrosine kinase inhibitors (lenvatinib, sorafenib, cabozantinib) and mutation-specific agents (selpercatinib, larotrectinib) on progression-free survival, and the theranostic perspective are evaluated in detail.Management algorithms, including active surveillance and compartment dissection for locoregional recurrences; the prognostic significance of parenchymal involvement patterns (micro-vs.macronodular) in pulmonary metastases; and multimodal strategies for skeletal metastases involving surgery, stereotactic body radiotherapy, and bonemodifying agents (denosumab, zoledronic acid) to prevent skeletal-related events that are presented in light of the updated American Thyroid Association 2025 and European Association of Nuclear Medicine/Society of Nuclear Medicine and Molecular Imaging guidelines.Furthermore, the role of fluorodeoxyglucose positron emission tomography/computed tomography within the context of the "flip-flop" phenomenon, redifferentiation protocols (mitogen-activated protein kinase/ proto-oncogene serine/threonine protein kinase inhibition), emerging theranostic targets such as fibroblast activation protein inhibitor and prostate-specific membrane antigen, and the clinical potential of alpha-emitting radionuclide zBu derleme, metastatik diferansiye tiroid kanseri (DTK) olgularnda radyoaktif iyot (RA) tedavisi, organ bazl lokal yaklamlar ve molekler hedefli sistemik tedavilerin gncel roln kapsaml biimde zetlemeyi amalamaktadr.zellikle RA-refrakter hastalk tanm; tirozin kinaz inhibitrleri (lenvatinib, sorafenib, kabozantinib) ve mutasyon spesifik (selperkatinib, larotrektinib) tedavilerin progresyonsuz sakalm zerindeki etkileri ile teranostik perspektif ele alnmtr.Lokorejyonel nkslerde aktif izlem ve kompartman diseksiyonu stratejileri; akcier metastazlarnda parankimal tutulum paternlerinin (mikro-makronodler) prognostik nemi; iskelet sistemi metastazlarnda ise iskelet ilikili olaylarn nlenmesine ynelik cerrahi, stereotaktik beden radyoterapisi ve kemik koruyucu ajanlar (denosumab, zoledronik asit) ieren multimodal ynetim algoritmalar gncel Amerikan Tiroid Birlii (American Thyroid Association) 2025 ve Avrupa Nkleer Tp Dernei/Nkleer Tp ve Molekler Grntleme Dernei klavuzlar nda sunulmutur.Ayrca "flip-flop" fenomeni balamnda florodeoksiglukoz pozitron emisyon tomografisi/bilgisayarl tomografinin yeri, rediferansiyasyon protokolleri (mitojenle aktive olan protein kinaz/proto-onkogen serin/treonin protein kinaz inhibisyonu) ve fibroblast aktivasyon proteini inhibitr, prostat spesifik membran antijeni gibi yeni teranostik hedeflerin yan sra alfa yayc radyonklid (astatin-211) tedavilerinin klinik potansiyeli tartlmtr.Metastatik DTK ynetiminde organ bazl