HoT – A phase III randomised trial to compare the rates of cancer returning in patients with low-risk differentiated thyroid cancer after a hemithyroidectomy and total thyroidectomy

Hemithyroidectomy or Total Thyroidectomy in 'low-risk' thyroid cancers

Status

Recruiting

Phases

Unknown

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN17004671

Enrollment

456

Registered

2022-02-22

Start date

2021-12-13

Completion date

Unknown

Last updated

2026-03-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Low risk thyroid cancers Cancer Malignant neoplasm of thyroid gland

Interventions

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):

Eligibility

Sex/Gender

All

Age

16 Years to 100 Years

Inclusion criteria

Inclusion criteria: Current key inclusion criteria as of 16/07/2025: Group 1 (Hemithyroidectomy already performed prior to diagnosis) 1. Aged 16 years or over 2. Papillary thyroid cancer (PTC): 2.1. pT1b-2 (=4cm) irrespective of molecular genetic markers 2.2. R0 resection (clinically excised but microscopic R1 resected tumours at discretion of the local multidisciplinary team (MDT)) 2.3. cN0 or pN0, pNX & pN1a (=5 foci, no extranodal spread) 2.4. Confined to thyroid or minimal extrathyroidal extension 2.5. No higher risk histological variants on morphology (small foci allowed at the discretion of the local MDT) 2.6. No angioinvasion 2.7. Encapsulated follicular variant of PTC with capsular invasion only 2.8. Micro-PTC (=1cm) - multifocal - unifocal with pN1a (=5 foci; no extranodal spread) 3. Follicular thyroid cancer and oncocytic/Hurthle cell carcinoma: 3.1. 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) 3.2. Confined to thyroid or minimal extrathyroidal extension Group 2 (Differentiated Thyroid Cancer on cytology/core biopsy, who has not had prior thyroid surgery yet) 1. Aged 16 or over 2. ‘low risk’ differentiated thyroid cancer confirmed by cytology or core biopsy. 3. cT1b-2 irrespective of molecular genetic markers 4. cN0 5. Contralateral lobe without suspicious nodule(s) (U2, or U3/U4 with Thy2 on FNAC) Eligibility criteria for nested sub-study on OpenClinica Participate’s web-based app (software): 1. Have a SMS enabled mobile phone or handheld tablet with web access 2. Are able to use the web-based app to complete the trial questionnaires without assistance Previous key inclusion criteria: Group 1 (Hemithyroidectomy already performed prior to diagnosis) 1. Aged 16 or over 2. Papillary thyroid cancer (PTC): 2.1. pT1b-2 (=4cm) irrespective of molecular genetic markers 2.2. R0 resection (clinically excised but microscopic R1 resected tumours at discretion of the local multidisciplinary team (MDT)) 2.3. cN0 or pN0, pNX & pN1a (=5 foci, no extranodal spread) 2.4. Confined to thyroid or minimal extrathyroidal extension 2.5. No higher risk histological variants on morphology (small foci allowed at the discretion of the local MDT) 2.6. No angioinvasion 2.7. Encapsulated follicular variant of PTC with capsular invasion only 2.8. Micro-PTC (=1cm) - multifocal - unifocal with pN1a (=5 foci; no extranodal spread) 3. Follicular thyroid cancer and oncocytic/Hurthle cell carcinoma: 3.1. 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) 3.2. Confined to thyroid or minimal extrathyroidal extension Group 2 (Differentiated Thyroid Cancer on cytology/core biopsy, who has not had prior thyroid surgery yet) 1. Aged 16 or over 2. ‘low risk’ differentiated thyroid cancer confirmed by cytology or core biopsy. 3. cT1b-2 irrespective of molecular genetic markers 4. cN0 5. Contralateral lobe without suspicious nodule(s) (U2, or U3/U4 with Thy2 on FNAC) Eligibility criteria for nested sub-study on Navio’s web-based app (software): 1. Have a SMS enabled mobile phone or handheld tablet with web access 2. Are able to use the web-based app to complete the trial questionnaires without assist

Exclusion criteria

Exclusion criteria: Group 1 (Hemithyroidectomy already performed prior to diagnosis): 1. Tumour > 4cm 2. Unifocal pT1a ( 5 foci or extranodal spread 9. pN1b 10. M1 11. 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 12. FTC and oncocytic/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 (Differentiated thyroid cancer on cytology or after core biopsy, who has not had prior thyroid surgery yet) 1. M1

Design outcomes

Primary

Measure	Time frame
Recurrence rate at 3 years follow-up defined as thyroid cancer recurrence, metastatic disease or death from thyroid cancer (whichever occurs first), timed from date of surgery to 3 year follow up, analysed using Kaplan-Meier curves and Cox regression.	—

Secondary

Measure	Time frame
Current secondary outcome measures as of 16/07/2025: 1. Recurrence rate at 5-year follow-up defined as thyroid cancer recurrence, metastatic disease or death from thyroid cancer (whichever occurs first), timed from date of surgery to 5-year follow-up, analysed using Kaplan-Meier curves and Cox regression. 2. Anatomical site of recurrences measured using a frequency table and Fisher's exact test at 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. 3. Risk of loco-regional recurrence based on time to recurrence measured using Cox regression at 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. 4. Number and type of additional investigations and procedures after surgery measured using a frequency table and Fishers exact test at 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery 5. Surgical complications and severity, including voice function measured using CTCAE v5.0 and the highest grade of each event type for each patient. These will be compared using a frequency table and Fishers exact test where appropriate, measured prior to discharge post-surgery, 2-4 weeks, 6 months and 18 months from date of surgery. Voice function will also be measured using the Voice Handicap Index questionnaire (VHI-10) at baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. 6. Requirement for hormone replacement therapy defined as the percentage of patients who require this therapy will be compared between the trial arms using a chi-squared test of two proportions at 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. 7. Quality of life (QoL) measured using questionnaires: EORTC QLQ-C30, EORTC QLQ-THY35, EQ5D-5L; and FoP-Q-SF (Short Form of the Fear of Progression). These will be collected at baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. QoL will be analysed using repeated measures regression analyses. 8. Cost and healt	—

Measure

Time frame

Current secondary outcome measures as of 16/07/2025: 1. Recurrence rate at 5-year follow-up defined as thyroid cancer recurrence, metastatic disease or death from thyroid cancer (whichever occurs first), timed from date of surgery to 5-year follow-up, analysed using Kaplan-Meier curves and Cox regression. 2. Anatomical site of recurrences measured using a frequency table and Fisher's exact test at 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. 3. Risk of loco-regional recurrence based on time to recurrence measured using Cox regression at 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. 4. Number and type of additional investigations and procedures after surgery measured using a frequency table and Fishers exact test at 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery 5. Surgical complications and severity, including voice function measured using CTCAE v5.0 and the highest grade of each event type for each patient. These will be compared using a frequency table and Fishers exact test where appropriate, measured prior to discharge post-surgery, 2-4 weeks, 6 months and 18 months from date of surgery. Voice function will also be measured using the Voice Handicap Index questionnaire (VHI-10) at baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. 6. Requirement for hormone replacement therapy defined as the percentage of patients who require this therapy will be compared between the trial arms using a chi-squared test of two proportions at 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. 7. Quality of life (QoL) measured using questionnaires: EORTC QLQ-C30, EORTC QLQ-THY35, EQ5D-5L; and FoP-Q-SF (Short Form of the Fear of Progression). These will be collected at baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery. QoL will be analysed using repeated measures regression analyses. 8. Cost and healt

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Countries

England, Scotland, United Kingdom, Wales

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Apr 3, 2026