Active Surveillance for Bethesda IV Thyroid Nodules

NCT07370675 | Recruiting

• 1 other identifier: 25047119
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

The traditional surgical approach for Bethesda IV thyroid nodules burdens healthcare systems and patients with costs, perioperative morbidity, and potential long-term consequences of hemithyroidectomy, including hypothyroidism (requiring lifelong thyroid hormone replacement), nerve damage, infection, voice discomfort and postoperative bleeding. Moreover, patient-reported anxiety and reduced quality of life often follow surgery, regardless of benign final pathology. Conversely, surveillance strategies that include periodic ultrasound assessment, clinical examination, and patient education may reduce overtreatment, preserve thyroid function, and optimize resource utilization. This prospective cohort protocol seeks to address these gaps by systematically evaluating the safety, feasibility, patient experience, and clinicopathologic predictors of progression for Bethesda IV nodules \<2 cm managed with active surveillance. Our hypothesis is: In patients with thyroid nodules smaller than 2 cm and cytology consistent with Bethesda IV, active surveillance is a safe and feasible alternative to immediate surgery. We hypothesize that only a minority of patients will demonstrate clinically significant tumor progression or require surgical intervention within five years, and that prospective surveillance can prevent unnecessary thyroid operations without compromising patient safety or long-term outcomes. The primary aim of this study is to determine the proportion of patients with Bethesda IV thyroid nodules \<2 cm who undergo surgical intervention or experience disease progression over a 1-, 2- and 5 year AS period.

Conditions

Thyroid Cancer; Thyroid Nodule

Outcome Measures

Primary Outcomes (1)

• Number of participants who undergo surgical intervention or experience disease progression during active surveillance

  From enrollment in to active surveillance to the end of the follow-up programe at 5 years

Study Arms (1)

Active Surveillance

EXPERIMENTAL

Active surveillance with ultrasound and clinical follow-up in a 5 year period

Other: Active surveillance (6, 12, 18, 24, 36, 48, 60 months)

Interventions

Active surveillance (6, 12, 18, 24, 36, 48, 60 months) OTHER

Active Surveillance og thyroid nodules with Bethesda IV cytology instead of surgery (diagnostic hemithyroidectomy).

Active Surveillance

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age of 30 years or older AND
• a single nodule with a Follicular neoplasm or suspicious for a follicular neoplasm (category IV in the Bethesda system) AND
• tumor size of less than 2 cm in all dimensions AND
• EU-TIRADS 3 or 4 in Ultrasound imaging examination.

You may not qualify if:

• EU-TIRADS 5 in Ultrasound imaging examination.
• suspicion of disseminated disease because of PET-positive lymph nodes; suspect lymph-nodes by US or by CT-scan; or signs of capsular invasion of the tumor, or irregular shape or margins, extrathyroidal growth OR
• tumor placement at a high-risk location (in the thyroid capsule with extracapsular extension toward vessels, RLN, or the trachea) OR
• previous thyroid surgery OR
• concomitant hyperparathyroidism (ionized calcium \> 1.32 mmol/L and PTH \> 6 pmol/L) OR
• if the patient is pregnant OR
• If the patient is unable to give informed consent. OR
• If calcitonin is elevated above normal level

Sponsors & Collaborators

• Christian Grønhøj Larsen: lead
• Rigshospitalet, Denmark: collaborator

Study Sites (1)

Department of Otolaryngology, Head and Neck SurgeryRigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

MeSH Terms

Conditions

Thyroid Neoplasms; Thyroid Nodule

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Central Study Contacts

Nicoline Thorup, MD, PhD Fellow

CONTACT

0045 45356863; nicoline.thorup@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior registrar, PhD, DMSci, ass. prof.

Study Record Dates

• First Submitted: January 19, 2026
• First Posted: January 27, 2026
• Study Start: January 16, 2026
• Primary Completion (Estimated): January 16, 2033
• Study Completion (Estimated): January 16, 2033
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)