Comparing the Therapeutic Efficacy of Extended Isthmusectomy Versus Total Thyroidectomy for Isthmus Tumors of the Thyroid

Comparing the Therapeutic Efficacy of Extended Isthmusectomy Versus Total Thyroidectomy for Isthmus Tumors of the Thyroid: A Prospective, Multicenter, Open-Label, Randomized Controlled Trial.

Prospective randomized open phase III non-inferiority trial in cT1bN0N1aM0 isthmus tumors of the thyroid comparing: extended Isthmusectomy (Isthmusectomy + Central Neck Dissection)(experimental group) versus total thyroidectomy + Central Neck Dissection (reference group).

Study Overview

• Status: Not yet recruiting
• Conditions: Thyroid Cancer; Thymectomy
• Intervention / Treatment: Procedure: Total thyroidectomy; Procedure: Extended isthmusectomy

Detailed Description

The thyroid isthmus is a narrow structure connecting the two lobes of the thyroid. Papillary carcinoma arising from this site accounts for only 1-9% of all thyroid cancers. However, due to its unique anatomical location, it is more prone to extranodal extension and bilateral lymph node metastasis, exhibiting more aggressive biological behavior. The optimal extent of surgery remains controversial: total thyroidectomy facilitates postoperative radioactive iodine therapy and monitoring but results in permanent dependence on thyroid hormone replacement and increases the risk of complications such as hypocalcemia, adversely affecting patients' quality of life. In contrast, conservative approaches like extended isthmusectomy can preserve partial thyroid function, reduce complications, and maintain a better quality of life, making them particularly suitable for low-risk patients with small tumors and no metastasis. Existing retrospective studies indicate no significant difference in recurrence rates between the two surgical approaches, though the evidence remains limited. Therefore, this study aims to conduct a prospective, multicenter, open-label, parallel-controlled, randomized trial to directly compare total thyroidectomy and extended isthmusectomy in terms of postoperative recurrence rates, quality of life, and complications, thereby providing high-quality evidence for surgical decision-making.

• Study Type: Interventional
• Enrollment (Estimated): 520
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jingying Zhang, MD; Phone Number: +86 15024439310; Email: jyzhang_hz@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Age 18 years or older.

Diagnosis of low-risk differentiated thyroid cancer (papillary, follicular, or Hürthle cell carcinoma).

Unifocal tumor located in the thyroid isthmus, cT1b

No evidence of extrathyroidal extension, assessed by preoperative ultrasound.

Exclusion Criteria:

- Aggressive pathological subtypes (e.g., tall cell, clear cell, columnar cell, or diffuse sclerosing variants of papillary thyroid carcinoma, as well as poorly differentiated types).

cN1b.

M1

Combined with other suspicious thyroid nodules within the lobes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Total thyroidectomy; Patients randomised to this arm will undergo total thyroidectomy with bilateral central compartment (level VI) neck dissection	Procedure: Total thyroidectomy; Total Thyroidectomy with bilateral central compartment (level VI) neck dissection - surgical removal of entire thyroid gland and perform bilateral Level VI neck dissection. This is the standard treatment recommended by the Chinese Guidelines for the Diagnosis and Management of Thyroid Nodules and Differentiated Thyroid Cancer (2nd Edition). The participating surgeons all routinely perform complete central neck dissections. They were selected for this study due to their standardized technique, which ensures a consistent surgical approach.
Experimental: extended isthmusectomy; Patients randomised to this arm will undergo extended isthmusectomy (ensure R0 resection) with bilateral central compartment (level VI) neck dissection	Procedure: Extended isthmusectomy; Extended isthmusectomy with bilateral central compartment (level VI) neck dissection : Completely resect the isthmus and portions of the bilateral thyroid gland adjacent to the isthmus, ensuring an R0 resection margin for the tumor, while preserving at least more than half of the bilateral thyroid lobes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of 3-year recurrence	defined as thyroid cancer recurrence, metastatic disease from thyroid cancer (whichever occurs first)	maximum of 3 years after the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anatomical location of tumor recurrence		maximum of 3 years after the surgery
Risk of surgical site recurrence	recurrence occured in the thyroid bed	maximum of 3 years after the surgery
Health Related Quality of Life	Measured using FoP-Q-SF: Scales range from 12-60 with higher scores indicating greater fear of disease progression Measured using THYCA-Qol questionnaires: including 7 symptom dimensions and 6 single items. All items are rated on a 4-point scale (none, a little, quite a bit, very much), scored from 1 to 4. Higher scores on individual items indicate lower quality of life.	Baseline (post-randomisation/pre-surgery), 4 weeks and 3, 6,12 months after the surgery
Number of participants with Hormone Replacement Therapy	patients who require thyroxin intake	2-4 weeks and 3, 6, 12, 24, 36 months after the surgery
Rate of surgical complications	including transient/permanent hypoparathyroidism, transient/permanent recurrent laryngeal nerve injury, postoperative infection, and postoperative lymphatic fistula.	perioperatively, 2-4 weeks, 6 months after the surgery

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Zhiyu Li, MD, Thyroid surgery Department, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China

Study record dates

Study Major Dates

• Study Start (Estimated): December 19, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: surgery; thyroid cancer; isthmus
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms
• Other Study ID Numbers: 2025-1245

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No