Clinical trial NCT05604963: Hemithyroidectomy or Total-Thyroidectomy in 'Low-risk' Thyroid Cancers
Official title: Hemithyroidectomy or Total-Thyroidectomy in 'Low-risk' Thyroid Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Differentiated Thyroid Cancer
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2022-11-03
Enrollment: 456
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 3 Year Recurrence Rate
timeFrame: From surgery to any signs or symptoms of the cancer or death assessed up to a maximum of 3 years from surgery date
Secondary outcomes:
measure: 5 Year Recurrence Rate
timeFrame: From surgery to any signs or symptoms of the cancer or death assessed up to a maximum of 5 years from surgery date
measure: Anatomical Site of Recurrence
timeFrame: From surgery to confirmed recurrence assessed up to a maximum of 5 years from surgery date
measure: Risk of Loco-Regional Recurrence
timeFrame: From surgery to confirmed recurrence assessed up to a maximum of 5 years from surgery date
measure: Number of Additional Investigations and Procedures after Surgery
timeFrame: 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery
measure: Type of Additional Investigations and Procedures after Surgery
timeFrame: 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery
measure: Voice Function
timeFrame: 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.
measure: Surgical complications and severity
timeFrame: 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.
measure: Requirement for Hormone Replacement Therapy
timeFrame: From surgery date to discharge, 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
measure: Health Related Quality of Life
timeFrame: Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
measure: Health Related Quality of Life
timeFrame: Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
measure: Health Related Quality of Life
timeFrame: Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
measure: Health Related Quality of Life
timeFrame: Baseline (post-randomisation/pre-surgery), 2-4 weeks and 6, 18, 30, 42, 54, 66 and 78 months from date of surgery.
measure: Cost and Health Resource Use
timeFrame: 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
measure: Cost and Health Resource Use
timeFrame: 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
measure: Cost and Health Resource Use
timeFrame: 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
measure: Secondary Care Health Resource Use
timeFrame: 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
measure: Primary Care Health Resource Use
timeFrame: 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
Other outcomes:
Locations:
city: Crewe
country: United Kingdom
facility: Leighton Hospital
state: Cheshire
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Colchester
country: United Kingdom
facility: Colchester Hospital
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Falkirk
country: United Kingdom
facility: Forth Valley Royal Hospital
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow & Clyde
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospitals
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Lister Hospital
city: London
country: United Kingdom
facility: Northwick Park Hospital
city: London
country: United Kingdom
facility: St George's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospitals
city: London
country: United Kingdom
facility: University College London Hospital
city: Luton
country: United Kingdom
facility: Luton and Dunstable University Hospital
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Poole
country: United Kingdom
facility: University Hospitals Dorset NHS Foundation Trust
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
city: Reading
country: United Kingdom
facility: Royal Berkshire Hospital
city: Rhyl
country: United Kingdom
facility: Glan Clwyd Hospital (Betsi Cadwaladr University Health Board)
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
Study officials:
References: