Systematic Radioiodine Administration Versus Decision of Radioiodine Treatment Guided by a Post-operative Work-up

Inclusion Criteria:

• Subgroup of patients with differentiated thyroid cancer and intermediate-riskdefined as follows according to TNM 2017:

• Papillary thyroid cancer (PTC) without aggressive subtype, follicular thyroidcancer (FTC) (with < 4 foci of vascular invasion) or Hürthle cell carcinoma (HCC)

• T1b or T2 with minimal extra-thyroid extension into the perithyroidal softtissues and/or pN1 with largest nodal dimension between 2 and 10 mm, withoutextra-capsular invasion and with a number of metastatic nodes ≤ 10

• T1aN1 with largest nodal dimension between 2 and 10 mm, without extra-capsularinvasion and with a number of metastatic nodes ≤ 10

• Patient treated by total thyroidectomy with macroscopically complete tumor resection (R0 or R1) ± neck dissection

• Total thyroidectomy performed within 6 to 14 10 weeks before randomization

• Patient with or without anti-thyroglobulin antibodies (TgAb)

• No known distant metastases

• Normal post-operative neck ultrasound (US) or if doubtful US, negative cytology andnormal Tg value (<10 ng/ml) in FNA washout fluid

• Post-operative LT4 treatment initiated at least 6 weeks before randomization

• Performance Status 0 or 1

• Patients aged 18 years or older

• Signed informed consent form

• Patient who agrees to be followed annually during 5 years

• Patient affiliated to the French social security system

Exclusion Criteria:

• • Patients with:

• medullary or anaplastic thyroid cancer

• or poorly differentiated carcinoma

• or well differentiated FTC with at least more than 4 foci of vascular invasion

• or PTC with aggressive variants (tall cell or columnar cell carcinoma, diffusesclerosing papillary, hobnail variant)

• NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclearfeatures) • Low-risk or high-risk DTC patients according to ATA 2015, andintermediate-risk patients with extra-thyroid extension into the perithyroidalmuscles (pT3b according to pTNM 2017), and/or pN1 with nodal largest dimension >10 mm or with extra-capsular invasion or more than 10 metastatic nodes. Thisexcludes the following patients:

• All pT1a, pT3 or pT4

• pT1aN0/x with or without minimal extra-thyroid extension

• pT1bN0/x, pT2N0/Nx without minimal extra-thyroid extension

• pT1aN1 or pT1bN1 or pT2N1 without extra-thyroid extension and with nodallargest dimension <2mm

• pT1aN1 or pT1bN1 or pT2N1 without extra-thyroid extension and with nodallargest dimension >10mm

• pT2N0/Nx without extra-thyroid extension

• pT2N1 without extra-thyroid extension and with nodal largest dimension <2mm

• pT2N1 without extra-thyroid extension and with nodal largest dimension >10mm

• Surgery considered as macroscopically incomplete (R2)

• Patients who have undergone lobectomy only

• Post-operative neck US with metastatic lymph-nodes confirmed by cytologyor by increased Tg (>10 ng/ml) in FNA washout fluid

• Drugs affecting thyroid function including iodinated contrast agents inthe 6 weeks prior to randomization. Amiodarone should have been stopped atleast 1 year before randomization.

• Previous RAI treatment for thyroid cancer

• Pregnant or lactating women

• Any associated geographical, social or psychopathological condition thatcould compromise the patient's ability to participate in the study

• Patient deprived of liberty or placed under the authority of a tutor

• History of malignancy in the past 3 years, except skin cancer excludingmelanoma, carcinoma in situ of the cervix. Any other solid tumor orlymphoma (without bone marrow involvement) must have been treated and nothave shown signs of recurrence for at least 3 years