Abstract:

The “2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer” introduce significant updates in genotyping. This article systematically interpreted the role and clinical applications of genotyping in pre-diagnostic differentiation, post-diagnostic familial analysis, surgical approach guidance, postoperative recurrence risk stratification, as well as targeted therapy and immunotherapy with a focus on mutation-based medical decision-making. Key updates on standardized genotyping applications include: ① In pathological diagnosis, genotyping was first applied in pathological differentiation. The 2025 ATA guidelines further clarify the distribution patterns of different genetic mutations across pathological subtypes, enabling more precise classification, particularly for tumors of very low malignant potential, to avoid overtreatment.② In familial analysis and genetic counseling, systematic familial evaluation is recommended post-diagnosis. The 2025 ATA guidelines propose strict clinical evidence-based categorization and selective germline genetic testing, with tailored genetic counseling strategies based on genotype. ③ In surgical approach and recurrence risk stratification, the 2025 ATA guidelines refine the auxiliary role of genotyping in surgical decision-making and recurrence risk stratification, reiterating that genotyping complements traditional risk stratification systems. ④ In targeted therapy, the 2025 ATA guidelines establish genotyping-guided precision therapy, mandating genetic testing for all radioiodine-refractory differentiated thyroid cancer (DTC) patients before targeted therapy to select mutation-specific agents. For patients progressing on target-specific drugs, re-biopsy is recommended to identify actionable targets. If no treatable target exists, multi-kinase inhibitors are advised. ⑤ In immunotherapy, pre-treatment genetic testing is recommended, with immunotherapy indicated for radioiodine-refractory DTC patients exhibiting high tumor mutational burden (TMB-H). This article provided a comprehensive review and in-depth analysis of the clinical applications of genotyping in DTC management as outlined in the 2025 ATA guidelines.

Key words: Differentiated thyroid cancer, Guideline, Genotyping, Clinical Management, Precision diagnosis and treatment