# Thyroid cancer

Source: https://nuclide.cc/indications/thyroid/  
Nuclide record `thyroid` (Indication). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Thyroid cancer is usually curable with surgery and radioactive iodine, the original theranostic. Rare aggressive forms respond to RET and BRAF inhibitors.

## Summary

Thyroid cancer is really several diseases. Differentiated thyroid cancer (papillary ~85%, follicular, oncocytic) arises from follicular cells, retains iodine uptake, and has a 10-year survival above 95%; its incidence has tripled in many countries because ultrasound finds tiny tumours that would never have caused harm. Medullary thyroid cancer comes from calcitonin-producing C cells, is driven by RET mutations (hereditary in MEN2), and does not take up iodine. Anaplastic thyroid cancer is rare, dedifferentiated, and historically progressed within months; BRAF/MEK inhibition and immunotherapy have started to change that.

Differentiated disease is treated by surgery, with radioactive iodine (the first theranostic, 1946) reserved for intermediate and high-risk patients after HiLo, ESTIMABL2, and IoN showed low-risk patients gain nothing from it; active surveillance is accepted for microcarcinomas, and lobectomy suffices for many. When cancer becomes radioiodine-refractory, lenvatinib (SELECT) and sorafenib (DECISION) extend progression-free survival, and genotype directs selective therapy: selpercatinib for RET fusions, larotrectinib for NTRK, dabrafenib-trametinib for BRAF. Medullary cancer moved from vandetanib and cabozantinib to RET-selective selpercatinib after LIBRETTO-531 (2023). Anaplastic cancer with BRAF V600E responds to dabrafenib-trametinib (ROAR), often enabling surgery, and triplets with pembrolizumab are producing multi-year survivors.

The field's biggest problems are the opposite of most cancers': over-detection and over-treatment of indolent disease, alongside the unsolved lethality of anaplastic and RAI-refractory disease, resistance to RET inhibitors (solvent-front mutations), and the toxicity of long-term multikinase therapy.

## Fields

- Kind: Indication
- Last checked: 2026-09-04
- Tags: endocrine; spike
- Group: endocrine
- Burden: ~820,000 cases per year; most are indolent papillary cancers with >98% survival.
- Subtypes: Papillary (~85%; BRAF V600E ~50%, RET/PTC fusions, RAS); Follicular (RAS, PAX8-PPARG); Oncocytic (Hürthle cell); Poorly differentiated; Anaplastic (BRAF V600E ~40%, TP53, TERT); Medullary (RET germline in MEN2 ~25%; somatic RET M918T); Papillary microcarcinoma (≤1 cm; surveillance candidate); Paediatric differentiated thyroid cancer (fusion-driven, often nodal, excellent survival)
- Biomarkers: BRAF V600E; RET fusion/mutation; NTRK; RAS; TERT; Thyroglobulin and anti-Tg antibodies (surveillance of differentiated cancer); Calcitonin and CEA (medullary); Germline RET (MEN2 screening, prophylactic thyroidectomy); Somatic RET fusion/mutation (selpercatinib); BRAF V600E (prognosis; anaplastic targeted therapy; redifferentiation); TERT promoter (aggressiveness); NTRK, ALK fusions (tumour-agnostic drugs); Bethesda cytology category and molecular classifier result; Radioiodine avidity on diagnostic scan

## Standard of care

- Differentiated: Thyroidectomy ± radioactive iodine; TSH suppression. ([Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/))
- Advanced/refractory: Lenvatinib; selpercatinib (RET); BRAF/MEK (anaplastic).
- Nodule work-up: Ultrasound with TI-RADS; FNA only for nodules meeting size/appearance thresholds; Bethesda reporting; molecular classifier (Afirma, ThyroSeq) for indeterminate results.
- Papillary microcarcinoma (≤1 cm, no spread): Active surveillance or lobectomy; total thyroidectomy and radioiodine not indicated.
- Low-risk differentiated (pT1-T2 N0): Lobectomy or total thyroidectomy; no radioiodine ablation (ESTIMABL2, IoN); modest TSH suppression then normal-range TSH. ([ESTIMABL2](https://nuclide.cc/trials/estimabl2/), [IoN](https://nuclide.cc/trials/ion-trial/))
- Intermediate/high-risk differentiated: Total thyroidectomy with therapeutic node dissection; radioiodine (1.1-3.7 GBq adjuvant; higher for known metastases) after recombinant TSH; TSH suppression. ([Radioactive iodine (I-131)](https://nuclide.cc/drugs/radioactive-iodine/), [Radioiodine therapy and whole-body iodine scanning](https://nuclide.cc/technologies/radioiodine-therapy/), [HiLo](https://nuclide.cc/trials/hilo/))
- Radioiodine-refractory, progressive: Genotype first: selpercatinib (RET fusion), larotrectinib/entrectinib (NTRK), dabrafenib-trametinib (BRAF V600E); otherwise lenvatinib (or sorafenib); consider MAPK-inhibitor redifferentiation to restore iodine uptake. ([SELECT](https://nuclide.cc/trials/select-lenvatinib/), [DECISION](https://nuclide.cc/trials/decision-sorafenib/))
- Medullary, localised: Total thyroidectomy with central neck dissection; prophylactic thyroidectomy in RET germline carriers by codon-based age; calcitonin surveillance.
- Medullary, advanced progressive RET-mutant: Selpercatinib first line (LIBRETTO-531); cabozantinib or vandetanib if RET-selective therapy unavailable or failed.
- Anaplastic, BRAF V600E: Rapid BRAF testing; dabrafenib-trametinib (ROAR), often with pembrolizumab, then surgery and radiation if rendered resectable.
- Anaplastic, BRAF wild-type: Multimodal chemoradiation (paclitaxel-based) if feasible; lenvatinib; immunotherapy for PD-L1-high or TMB-high; NTRK/RET/ALK agents if fusion-positive; early palliative care. ([Pembrolizumab](https://nuclide.cc/drugs/pembrolizumab/))
- Survivorship: Lifelong levothyroxine with risk-adapted TSH targets; calcium/PTH monitoring after surgery; salivary care after radioiodine; low-risk patients can be discharged to primary care.

## State of the art

- Genotype-directed therapy for aggressive subtypes.
- De-escalation is the story: radioiodine omitted for low-risk disease (ESTIMABL2, IoN), low-dose ablation when needed (HiLo), lobectomy and active surveillance for small tumours.
- Genotype-directed therapy covers most aggressive disease: RET (selpercatinib beat multikinase inhibitors head to head), BRAF, NTRK, ALK.
- Anaplastic thyroid cancer with BRAF V600E has moved from a median survival under six months to 15 months with the doublet and longer with immunotherapy added, and neoadjuvant use enables surgery.
- Molecular classifiers on needle biopsies have halved diagnostic surgery for indeterminate nodules.
- Redifferentiation with MAPK inhibitors can restore radioiodine uptake in about half of refractory patients.

## Open problems

- Overdiagnosis of microcarcinoma.
- Anaplastic thyroid cancer: BRAF V600E cases now respond to dabrafenib-trametinib, often enough to allow surgery; the 60% without the mutation still have few options.
- Overdiagnosis: incidence has tripled with no change in mortality; most detected cancers would never have caused harm, yet surveillance uptake outside Japan and Korea remains low.
- Anaplastic thyroid cancer without BRAF V600E (about 60%) still has a median survival of a few months.
- Resistance to RET-selective inhibitors via solvent-front (G810) mutations has no approved next-generation drug.
- Multikinase inhibitors for RAI-refractory disease cause hypertension, weight loss, and fatigue; most patients need dose reductions and quality of life suffers.
- No validated way to predict which low-risk patients will be the rare ones to recur, so follow-up intensity is uniform.
- Redifferentiation works in about half of refractory patients but predictors and optimal regimens are undefined.
- Paediatric and radiation-induced thyroid cancers (Chernobyl, Fukushima cohorts) have distinct fusion-driven biology that is under-studied.
- Hereditary MEN2 requires lifelong surveillance and prophylactic surgery in children; long-term outcomes of RET-selective therapy in this group are unknown.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Thyroid_cancer
- Wikipedia: https://en.wikipedia.org/wiki/Thyroid_cancer

## Connected records

- roadmaps: [Radiopharmaceutical roadmap: iodine → lutetium → actinium](https://nuclide.cc/roadmaps/radiopharma-roadmap/)
- terms: [Radioiodine therapy (I-131)](https://nuclide.cc/terms/radioiodine-term/), [Theranostics](https://nuclide.cc/terms/theranostics/)
- technologies: [Radioiodine therapy and whole-body iodine scanning](https://nuclide.cc/technologies/radioiodine-therapy/), [Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/), [SPECT/CT](https://nuclide.cc/technologies/spect-ct/), [Targeted alpha therapy](https://nuclide.cc/technologies/targeted-alpha-therapy/)
- drugs: [AL2846](https://nuclide.cc/drugs/al2846/), [Cabozantinib](https://nuclide.cc/drugs/cabozantinib/), [Donafenib](https://nuclide.cc/drugs/donafenib/), [Pembrolizumab](https://nuclide.cc/drugs/pembrolizumab/), [Radioactive iodine (I-131)](https://nuclide.cc/drugs/radioactive-iodine/), [Sorafenib](https://nuclide.cc/drugs/sorafenib/), [Thyrotropin alfa](https://nuclide.cc/drugs/thyrotropin-alfa/)
- companies: [AstraZeneca](https://nuclide.cc/companies/astrazeneca/), [Bayer](https://nuclide.cc/companies/bayer/), [Eli Lilly (incl. Loxo)](https://nuclide.cc/companies/eli-lilly/), [Novartis](https://nuclide.cc/companies/novartis/)
- institutions: [King Faisal Specialist Hospital and Research Centre](https://nuclide.cc/institutions/kfshrc/), [MD Anderson Cancer Center](https://nuclide.cc/institutions/md-anderson/), [Memorial Sloan Kettering Cancer Center](https://nuclide.cc/institutions/mskcc/)
- trials: [A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid Carcinoma](https://nuclide.cc/trials/nct06860971/), [A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Va](https://nuclide.cc/trials/nct03690388/), [ASTRA](https://nuclide.cc/trials/astra/), [DECISION](https://nuclide.cc/trials/decision-sorafenib/), [ESTIMABL2](https://nuclide.cc/trials/estimabl2/), [HiLo](https://nuclide.cc/trials/hilo/), [IoN](https://nuclide.cc/trials/ion-trial/), [SELECT](https://nuclide.cc/trials/select-lenvatinib/), [Study of ST-1898 in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Cancer](https://nuclide.cc/trials/nct06359847/)
- indications: [Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)](https://nuclide.cc/indications/multiple-endocrine-neoplasia/)
- isotopes: [Iodine-123](https://nuclide.cc/isotopes/i-123/), [Iodine-124](https://nuclide.cc/isotopes/i-124/), [Iodine-131](https://nuclide.cc/isotopes/i-131/)
- targets: [CCK2 receptor (gastrin receptor)](https://nuclide.cc/targets/cck2-receptor/), [NIS (sodium-iodide symporter)](https://nuclide.cc/targets/nis-symporter/)

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JSON: https://nuclide.cc/api/v1/entities/thyroid.json