About the study

Thyroid nodules classified as Bethesda category IV may represent either benign lesions or malignant tumours. Current diagnostic methods are unable to reliably distinguish between these possibilities before surgery.

As a result, many patients undergo diagnostic surgery primarily to obtain tissue for histopathological evaluation. However, malignancy is ultimately confirmed in only approximately 15–20% of operated patients, meaning that most procedures serve mainly to exclude cancer.

Surgical treatment may involve discomfort, scarring, healthcare costs and the risk of complications such as recurrent laryngeal nerve injury, hypoparathyroidism or hypothyroidism.

Why is a new diagnostic approach needed?

Researchers are seeking minimally invasive methods that can distinguish benign lesions from malignant tumours before surgery in patients with Bethesda IV thyroid nodules.

A more accurate preoperative diagnosis could reduce the number of unnecessary surgical procedures and reserve surgery for patients who truly require it.

What is multimodal ultrasound?

Multimodal ultrasound (mpUS) combines several advanced ultrasound imaging techniques during a single examination.

These techniques include shear-wave elastography (SWE), which evaluates tissue stiffness, and contrast-enhanced ultrasound (CEUS), which assesses blood flow and microcirculation patterns.

Together, these methods provide additional information about the internal structure of thyroid nodules and their surrounding tissues beyond that available from standard ultrasound imaging.

Study design

The study enrols patients awaiting diagnostic and therapeutic surgery for thyroid nodules classified as Bethesda category IV.

Participants are randomly assigned to one of two groups:

• multimodal ultrasound assessment using an extended imaging protocol;
• standard ultrasound assessment according to routine clinical practice.

Based on ultrasound findings, lesions are classified as sonographically benign or sonographically malignant.

Histopathological examination of tissue obtained during surgery serves as the reference standard for comparing the diagnostic accuracy of both ultrasound approaches.

Primary endpoint

The primary endpoint is the correct classification of Bethesda IV thyroid nodules as benign or malignant based on ultrasound findings, using histopathological diagnosis as the reference standard.

Secondary endpoints

• differences in multimodal ultrasound parameters between benign and malignant tumours;
• frequency of adverse events in the study and control groups;
• cost-effectiveness measured as the cost of extending preoperative ultrasound assessment per additional correct diagnosis or exclusion of malignancy.

Study hypothesis

The primary research hypothesis is that the rate of correct classifications will be at least 10% higher with multimodal ultrasound than with standard ultrasound assessment.

Study objectives

The aim of the project is to compare the effectiveness, safety and cost-effectiveness of multimodal ultrasound with standard ultrasound assessment in the preoperative identification of malignant thyroid tumours in patients with Bethesda IV thyroid nodules.

If the hypothesis is confirmed, the findings could support the introduction of multimodal ultrasound into routine clinical practice, reducing the number of diagnostic surgical procedures in favour of minimally invasive diagnostics

Study population

Eligible participants must meet all of the following criteria:

• age 18 years or older;
• thyroid nodule classified cytologically as Bethesda category IV;
• qualification for diagnostic and therapeutic surgery based on the thyroid lesion.

Exclusion criteria include:

• lesion size below 5 mm;
• poor visibility of the lesion on standard ultrasound;
• lesion forming part of a conglomerate of adjacent nodules;
• pregnancy or breastfeeding.

Research team

The national coordinating investigator and principal investigator is Piotr Wiśniewski, MD, PhD from the Department and Clinic of Endocrinology and Internal Diseases at the Medical University of Gdańsk.

Organisational information

The project is funded by the Polish state budget through the Medical Research Agency (MRA) under the head-to-head clinical trials funding call ABM/2022/3

Project number: 2022/ABM/03/00010.

Project duration: 02 May 2023 – 31 October 2027.

Funding and total project value: PLN 823,919.91.