Hemithyroidectomy or Total-Thyroidectomy in 'Low-risk' Thyroid Cancers (HoT)

This is a multi-centre, randomised, non-inferiority, phase III study in patients with low risk differentiated thyroid cancer.

Patients will be identified via oncology multidisciplinary team meetings. There will be two sources of patients in the trial, with the same histological diagnoses and prognosis (i.e. recurrence risk):

• Group 1: Patients who have already had a HT for thyroid problems and are then subsequently diagnosed with low risk DTC will be randomised 1:1 to undergo surveillance only OR a second operation to remove the rest of their thyroid gland (two-stage total thyroidectomy).
• Group 2: Patients diagnosed with low risk DTC using cytology (Thy5) but no surgery performed will be randomised 1:1 to have either a hemi-thyroidectomy OR a single-stage total thyroidectomy.

The overall aim of the trial is to determine whether hemithyroidectomy is an acceptable and cost-effective surgical procedure compared to total thyroidectomy in low risk thyroid cancer. Overall, 456 patients will be recruited to the trial. Patients will be initially be followed up post-surgery then 12 monthly for 6 years.

Study Overview

• Status: Recruiting
• Conditions: Differentiated Thyroid Cancer
• Intervention / Treatment: Procedure: Total Thyroidectomy; Procedure: Hemithyroidectomy

• Study Type: Interventional
• Enrollment (Estimated): 456
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jeannie Chamberlain; Phone Number: 020 3108 4875; Email: ctc.hot@ucl.ac.uk

Study Locations

• United Kingdom
  • Bath, United Kingdom
    • Not yet recruiting
    • Royal United Hospital
    • Principal Investigator: Andrew Carswell
  • Birmingham, United Kingdom
    • Recruiting
    • Queen Elizabeth Hospital
    • Principal Investigator: Neil Sharma
  • Bristol, United Kingdom
    • Recruiting
    • University Hospitals Bristol and Weston NHS Foundation Trust
    • Principal Investigator: Oliver Dale
  • Cambridge, United Kingdom
    • Recruiting
    • Addenbrooke's Hospital
    • Principal Investigator: Brian Fish
  • Cardiff, United Kingdom
    • Recruiting
    • University Hospital of Wales
    • Principal Investigator: Michael Stechman
  • Colchester, United Kingdom
    • Recruiting
    • Colchester Hospital
    • Principal Investigator: Abdul Qureshi
  • Derby, United Kingdom
    • Recruiting
    • Royal Derby Hospital
    • Principal Investigator: Hazem Nijim
  • Dundee, United Kingdom
    • Recruiting
    • Ninewells Hospital
    • Principal Investigator: Jaiganesh Manickavasagam
  • Edinburgh, United Kingdom
    • Recruiting
    • Nhs Lothian
    • Principal Investigator: Iain Nixon
  • Exeter, United Kingdom
    • Recruiting
    • Royal Devon and Exeter Hospital
    • Principal Investigator: Joel Smith
  • Falkirk, United Kingdom
    • Recruiting
    • Forth Valley Royal Hospital
    • Principal Investigator: Michail Winkler
  • Gillingham, United Kingdom
    • Recruiting
    • Medway Maritime Hospital
    • Principal Investigator: Maria Acosta
  • Glasgow, United Kingdom
    • Recruiting
    • NHS Greater Glasgow & Clyde
    • Principal Investigator: Catriona Douglas
  • Ipswich, United Kingdom
    • Recruiting
    • Ipswich Hospital
    • Principal Investigator: Billy Wong
  • Leicester, United Kingdom
    • Recruiting
    • Leicester Royal Infirmary
    • Principal Investigator: Oladejo Olaleye
  • Liverpool, United Kingdom
    • Recruiting
    • Liverpool University Hospitals
    • Principal Investigator: Christopher Loh
  • London, United Kingdom
    • Recruiting
    • Northwick Park Hospital
    • Principal Investigator: Zi Wei Liu
  • London, United Kingdom
    • Recruiting
    • Guy's Hospital
    • Principal Investigator: Ricard Simo
  • London, United Kingdom
    • Recruiting
    • St George's Hospital
    • Principal Investigator: Enyinnaya Ofo
  • London, United Kingdom
    • Recruiting
    • Lister Hospital
    • Principal Investigator: George Mochloulis
  • London, United Kingdom
    • Recruiting
    • The Royal Marsden Hospitals
    • Principal Investigator: Vinidh Paleri
  • London, United Kingdom
    • Not yet recruiting
    • University College London Hospital
    • Principal Investigator: Tarek Abdel-Aziz
  • Luton, United Kingdom
    • Recruiting
    • Luton and Dunstable University Hospital
    • Principal Investigator: Tarun Sood
  • Northampton, United Kingdom
    • Recruiting
    • Northampton General Hospital
    • Principal Investigator: Rohan Bidaye
  • Norwich, United Kingdom
    • Recruiting
    • Norfolk and Norwich University Hospital
    • Principal Investigator: Ramez Nassif
  • Nottingham, United Kingdom
    • Not yet recruiting
    • Nottingham University Hospitals NHS Trust
    • Principal Investigator: Neeraj Sethi
  • Plymouth, United Kingdom
    • Recruiting
    • Derriford Hospital
    • Principal Investigator: Richard Williams
  • Poole, United Kingdom
    • Recruiting
    • University Hospitals Dorset NHS Foundation Trust
    • Principal Investigator: Neil De Zoysa
  • Portsmouth, United Kingdom
    • Recruiting
    • Queen Alexandra Hospital
    • Principal Investigator: Costa Repanos
  • Rhyl, United Kingdom
    • Recruiting
    • Glan Clwyd Hospital (Betsi Cadwaladr University Health Board)
    • Principal Investigator: Kym Best
  • Sheffield, United Kingdom
    • Recruiting
    • Sheffield Teaching Hospitals
    • Principal Investigator: Saba Balasubramanian
  • Taunton, United Kingdom
    • Recruiting
    • Musgrove Park Hospital
    • Principal Investigator: Edward Chisholm
  • Cheshire
    • Crewe, Cheshire, United Kingdom, CW1 4QJ
      • Recruiting
      • Leighton Hospital
      • Principal Investigator: Eriola Mushi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Group 1 (HT already performed prior to diagnosis)

Inclusion criteria

• Aged 16 or over

Papillary thyroid cancer:

• pT1b-2 (≤4cm) irrespective of molecular genetic markers
• R0 resection (clinically excised but microscopic R1 resected tumours at discretion of the local MDT)
• cN0 or pN0, pNX & pN1a (≤5 foci, no extranodal spread)
• Confined to thyroid or minimal extrathyroidal extension
• No higher risk histological variants on morphology (small foci allowed at the discretion of the local MDT)
• No angioinvasion NB. PTC is still eligible where microscopic invasion of endothelial lined small capillary vascular spaces and lymphatic channels are present. It becomes ineligible in the rare instances when there is definite invasion of a larger vascular structure such as a vein with smooth muscle in its wall.
• Encapsulated FVPTC with capsular invasion only

• Micro-PTC (≤1cm)

  • multifocal
  • unifocal with pN1a (≤5 foci; no extranodal spread)

Follicular thyroid cancer (FTC), including oncocytic or Hürthle cell carcinoma:

• pT1b-2 (≤4cm) irrespective of molecular genetic markers

  - Minimally invasive, with capsular invasion +/- minimal (≤4 foci) vascular invasion (the latter is now called encapsulated angioinvasive and is at the discretion of the MDT)

• Confined to thyroid or minimal extrathyroidal extension

Exclusion criteria

• >4cm
• unifocal pT1a (≤1cm) PTC or FTC (unless pN1a as above)
• NIFTP (non-invasive follicular thyroid neoplasm with papillary-like nuclear features)
• Anaplastic, poorly differentiated or medullary thyroid carcinoma
• R2
• gross extrathyroidal extension
• pT4 or macroscopic tumour invasion of loco-regional tissues or structures
• pN1a with >5 foci or extranodal spread
• pN1b
• M1

• Aggressive PTC with any of the following features:

  • Widely invasive
  • Poorly differentiated
  • Anaplastic
  • predominance of Tall cell, Columnar cell, Hobnail, Diffuse sclerosing and other higher risk variants

• FTC, including oncocytic or Hürthle cell cancer with any of the following features:

  • Minimally invasive with extensive vascular invasion (now called encapsulated angioinvasive) (>4 foci)
  • Widely invasive
  • Poorly differentiated
  • Anaplastic

Group 2 (DTC on cytology or after core biopsy, who has not had prior thyroid surgery yet)

Inclusion criteria

• Aged 16 or over
• 'low risk' differentiated thyroid cancer confirmed by cytology or core biopsy.
• cT1b-2 irrespective of molecular genetic markers
• cN0
• Contralateral lobe without suspicious nodule(s) (U2, or U3/U4 with Thy2 on FNAC)

Exclusion criteria

• M1

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1: Two-stage Completion Thyroidectomy; Patients randomised to this arm will undergo a 2nd operation to remove the remaining thyroid lobe.	Procedure: Total Thyroidectomy; Total Thyroidectomy - surgical removal of entire thyroid gland
No Intervention: Group 1: Surveillance; Patients randomised to this arm will have no 2nd surgery and proceed directly to follow-up visits.
Experimental: Group 2: Hemi-thyroidectomy; Patients randomised to this arm will have a single HT operation to remove thyroid lobe with the tumour.	Procedure: Hemithyroidectomy; Hemithyroidectomy - surgical removal of partial thyroid gland
Active Comparator: Group 2: Total Thyroidectomy; Patients randomised to this arm will have a single TT operation to remove the entire thyroid gland.	Procedure: Total Thyroidectomy; Total Thyroidectomy - surgical removal of entire thyroid gland

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 Year Recurrence Rate	(defined as thyroid cancer recurrence, metastatic disease or death from thyroid cancer (whichever occurs first))	From surgery to any signs or symptoms of the cancer or death assessed up to a maximum of 3 years from surgery date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5 Year Recurrence Rate	(defined as thyroid cancer recurrence, metastatic disease or death from thyroid cancer (whichever occurs first))	From surgery to any signs or symptoms of the cancer or death assessed up to a maximum of 5 years from surgery date
Anatomical Site of Recurrence	Location of recurrence	From surgery to confirmed recurrence assessed up to a maximum of 5 years from surgery date
Risk of Loco-Regional Recurrence	(based on time to recurrence in the neck only)	From surgery to confirmed recurrence assessed up to a maximum of 5 years from surgery date
Number of Additional Investigations and Procedures after Surgery	Number of further investigations/procedures related to the patient's thyroid surgery or thyroid cancer e.g. imaging, blood test, biopsy etc.	2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery
Type of Additional Investigations and Procedures after Surgery	Type of further investigations/procedures related to the patient's thyroid surgery or thyroid cancer e.g. imaging, blood test, biopsy etc.	2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery
Voice Function	Measured using the Voice Handicap Index questionnaire (VHI-10); scores range from 0-40 with higher scores indicating greater voice-related handicap	Surgical complications and severity: From surgery date to discharge, 2-4 weeks, 6 months and 18 months from date of surgery; Voice Function: Post-randomisation/pre-surgery, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Surgical complications and severity	Using CTCAE v5.0 and the highest grade of each event type for each patient	Surgical complications and severity: From surgery date to discharge, 2-4 weeks, 6 months and 18 months from date of surgery; Voice Function: Post-randomisation/pre-surgery, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Requirement for Hormone Replacement Therapy	(percentage of patients who require this therapy compared between the trial arms)	From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Secondary Care Health Resource Use	Collected using eCRFs and retrospectively for the study period from data in the Hospital Episodes Statistics linked to records in the NCRAS	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery
Primary Care Health Resource Use	Collected using eCRFs (Review of Primary Care Visits)	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery
Health Related Quality of Life (EORTC QLQ-C30)	Measured using EORTC QLQ-C30; Scales range from 0-100 with higher scores for the functioning scales and global health status indicating higher QoL and higher scores on the symptom and single-item scales indicating lower QoL	Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Health Related Quality of Life (EORTC QLQ-THY35)	Measured using EORTC QLQ-THY35; Scales range from 0-100 with higher scores indicating higher QoL and lower scores indicating lower QoL	Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Health Related Quality of Life (EQ-5D-5L)	Measured using EQ-5D-5L; EQVAS score ranges from 0-100 with higher scores indicating higher QoL and lower scores indicating lower QoL; EQ-5D-5L index scores range from -0.224-1 with higher scores indicating higher QoL and lower scores indicating lower QoL	Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Health Related Quality of Life (FoP-Q-SF)	Measured using FoP-Q-SF; scores range from 12-60 with higher scores indicating lower QoL and lower scores indicating higher QoL	Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
Cost and Health Resource Use (EQ-5D-5L)	Measured using EQ-5D-5L (generic QoL)	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery
Cost and Health Resource Use (EORTC QLQ-C30)	Measured using EORTC QLQ-C30 (cancer-specific QoL)	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery
Cost and Health Resource Use (EORTC QLQ-THY34)	Measured using EORTC QLQ-THY34 (Cancer site specific QoL)	a. Baseline, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. b. From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 & 78 months from date of surgery. c/d. 6, 18, 30, 42, 54, 66 & 78 months from date of surgery

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Dae Kim, The Royal Marsden Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2031

Study Registration Dates

• First Submitted: July 22, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• 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: UCL/136591

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No