This study aims to investigate the efficacy and prognosis of ultrasound-guided and gene-based microwave ablation (MWA) versus surgical treatment in patients with low-risk papillary thyroid carcinoma (PTC). By analyzing genetic testing results, the study explores the impact of genetic mutations on treatment selection for low-risk patients, providing more precise molecular biological evidence for treatment choices and prognosis evaluation of thyroid cancer. This prospective study collects clinical data from patients diagnosed with PTC at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2022 and November 2024, who underwent genetic testing prior to treatment, and assesses efficacy and complications through long-term follow-up.

Objective: This study evaluates and compares the efficacy and prognosis of ultrasound and gene-based microwave ablation (MWA) and surgical treatment in patients with low-risk papillary thyroid carcinoma (PTC), emphasizing the influence of genetic mutations on low-risk patients' selection.

Background: MWA, a minimally invasive technique, is increasingly recognized in the management of PTC. While traditional criteria for ablation focus on tumor size, number, and location, the impact of genetic mutations on treatment efficacy remains underexplored.

Methods: A total of 201 patients with low-risk PTC without metastasis were prospectively enrolled. All patients underwent ultrasound and next-generation sequencing to confirm low-risk status. Patients chose either ablation or surgery and were monitored until November 2024. Efficacy and complications were assessed using thyroid ultrasound and contrast-enhanced ultrasound.

The inclusion criteria of this study were as followed:

1. PTC confirmed by fine-needle aspiration (FNA);
2. Confirmed low-risk mutation types by next-generation sequencing (NGS) before surgery;
3. No severe functional diseases, such as heart failure, severe respiratory diseases, or renal failure;
4. Availability of complete follow-up data.

The exclusion criteria were as followed:

1. No local or distant metastasis assessed by imaging evaluations, including ultrasound or computed tomography (CT);
2. Lacking of preoperative genetic testing or inability to assess genetic test results;
3. Inability to complete follow-up or lost to follow-up during the study.

Low-risk PTC is defined as:

1. Maximum tumor diameter ≤1 cm;
2. Solitary lesion;
3. No local or distant metastasis;
4. No tumor invasion into extrathyroidal tissues;
5. No vascular invasion;
6. Non-invasive pathological subtype for the primary lesion (invasive subtypes include tall cell, columnar cell, diffuse sclerosing, solid/trabecular, and oncocytic vari ants);
7. No history of head and neck radiotherapy during adolescence;
8. No family history of thyroid cancer;
9. Genetic testing showing BRAF V600E mutation (without concurrent TERT mutation), RAS family gene mutations, (HRAS, NRAS, KRAS), or other low-risk mutations, such as isolated RET/PTC) rearrangements.

Intermediate-high risk PTC is defined as:

1. Maximum tumor diameter >1 cm;
2. Multifocal thyroid cancer;
3. Local or distant metastasis;
4. Primary lesion with extrathyroidal extension;
5. Vascular invasion;
6. Primary lesion with an invasive pathological subtype;
7. History of head and neck radiotherapy during adolescence;
8. Family history of thyroid cancer;
9. Genetic testing revealing high-risk mutation combinations, such as BRAF V600E or RAS mutations with concurrent TERT or TP53 mutations, or RAS mutations combined with EIF1AX mutations.

The study population includes patients diagnosed with papillary thyroid carcinoma (PTC) at Sun Yat-Sen Memorial Hospital from January 2022 to November 2024. A total of 201 patients were prospectively enrolled in this study.