indicationsIndication

Thyroid cancer

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

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.

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.

Anatomy and lymph node drainage

Head and neck, salivary glands and thyroid: subsites and node stations · wireframe schematic, not to scale

Site decides cause and behaviour: HPV drives oropharyngeal cancer, EBV drives nasopharyngeal cancer, tobacco drives oral and laryngeal cancer; all drain into the neck node levels that surgeons and radiotherapists map.

Subsites

Oral cavity and tongueAnaplastic (BRAF V600E ~40%, TP53, TERT)
Oropharynx: tonsil, base of tongue (HPV)
Nasopharynx (EBV)
Larynx and hypopharynx
Parotid and other salivary glands
ThyroidPapillary (~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)

Regional lymph nodes

level I (submandibular)
level II (upper jugular)
level III-IV (jugular)
level V (posterior)
level VI (central, thyroid)
retropharyngeal (nasopharynx)

Same organ: Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)

Preclinical models

5 cell lines, 1 mouse models and 3 repositories are listed for this cancer.

Who gets it and what has changed

Show survival figures (1)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

~820,000 cases per year; most are indolent papillary cancers with >98% survival.

Group

endocrine

Advanced diseaseShow where advanced disease can reach, and what treats itThe sites decide which scans are done at staging and follow-up, and every site listed has a treatment approach.

Most people reading this do not have advanced disease. The map describes what can happen over the whole course of the illness, across autopsy and registry series; today's staging scans find spread earlier, and each site has treatments, from focused radiotherapy for a few spots to drugs that reach the brain.

What helpsRadioactive iodine treats spread that still takes up iodine; lenvatinib, selpercatinib (RET), dabrafenib-trametinib (BRAF) and redifferentiation for refractory disease. Neck-node spread has little effect on survival.

What is being done about this

Advanced and metastatic disease

Available now

Radioactive iodine (I-131)Approved
Radioligand therapy (beta emitters)Approved

In trials

Ideas and roadmaps

Nothing recorded yet.

Also on Nuclide: Indications.

Cervical lymph nodesmost common
Papillary cancer spreads to neck nodes early and often, with little effect on survival.
Lungscommon
Follicular cancer favours blood-borne spread to lung and bone.
Bonecommon
Brainrare
Liverrare

Standard of care

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Differentiated

Thyroidectomy ± radioactive iodine; TSH suppression.

NCCN Guidelines: Thyroid Carcinoma

Radioligand therapy (beta emitters)

Advanced/refractory

Lenvatinib; selpercatinib (RET); BRAF/MEK (anaplastic).

NCCN Guidelines: Thyroid Carcinoma

Nodule work-up

Ultrasound with TI-RADS; FNA only for nodules meeting size/appearance thresholds; Bethesda reporting; molecular classifier (Afirma, ThyroSeq) for indeterminate results.

NCCN · 2A

Papillary microcarcinoma (≤1 cm, no spread)

Active surveillance or lobectomy; total thyroidectomy and radioiodine not indicated.

NCCN · 2A

Low-risk differentiated (pT1-T2 N0)

Lobectomy or total thyroidectomy; no radioiodine ablation (ESTIMABL2, IoN); modest TSH suppression then normal-range TSH.

NCCN · 2A

ESTIMABL2 IoN

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.

NCCN · 2A

Radioactive iodine (I-131)Radioiodine therapy and whole-body iodine scanning 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.

NCCN · 1 (lenvatinib)ESMO-MCBS · 3

SELECT DECISION

Medullary, localised

Total thyroidectomy with central neck dissection; prophylactic thyroidectomy in RET germline carriers by codon-based age; calcitonin surveillance.

NCCN · 2A

Medullary, advanced progressive RET-mutant

Selpercatinib first line (LIBRETTO-531); cabozantinib or vandetanib if RET-selective therapy unavailable or failed.

NCCN · 1 (preferred)ESMO-MCBS · 3

Anaplastic, BRAF V600E

Rapid BRAF testing; dabrafenib-trametinib (ROAR), often with pembrolizumab, then surgery and radiation if rendered resectable.

NCCN · 2A

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

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.

Subtypes & biomarkers

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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 clinicians test

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

How often this target appears

History

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1946Radioactive iodine: first theranostic
1946First patient treated with radioactive iodine for metastatic thyroid cancer
Seidlin, Marinelli, and Oshry: the first theranostic.
Radioactive iodine (I-131)Radioiodine therapy and whole-body iodine scanning
1985RET proto-oncogene identified; MEN2 germline RET mutations follow (1993)
2003BRAF V600E found in ~45% of papillary thyroid cancers
2009Bethesda System for thyroid cytology standardises nodule reporting
2011Vandetanib: first drug for medullary thyroid cancer
2012HiLo and ESTIMABL1: low-dose radioiodine ablation is enough
HiLo
2013Sorafenib approved for RAI-refractory disease (DECISION); selumetinib redifferentiation proof of concept
DECISION
2015Lenvatinib approved (SELECT); ATA guidelines endorse active surveillance and less radioiodine
SELECT
2018Dabrafenib-trametinib approved for BRAF V600E anaplastic thyroid cancer (ROAR); larotrectinib tumour-agnostic
2020Selpercatinib approved
2020Selpercatinib and pralsetinib: RET-selective inhibitors approved
2022ESTIMABL2: no radioiodine for low-risk disease; ASTRA adjuvant redifferentiation negative
ESTIMABL2 ASTRA
2023LIBRETTO-531: selpercatinib beats cabozantinib/vandetanib in medullary cancer
2025IoN confirms omission of radioiodine in low-risk disease (Lancet)
IoN
2026Selpercatinib label update (July 2026)

What changed

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Dated changes read from the records linked to this indication: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 31 changes by month →

FollowWatch this record and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for Thyroid cancer, drawn from the whole corpus: 11 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Drugs in phase 3 · 1

Phase 3small molecule (structure undisclosed or not yet in PubChem)

AL2846

Technologies being tested · 1

Targeted alpha therapy

Trials under way · 3

A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid Carcinoma · phase 3 · Chia Tai Tianqing Pharmaceutical
A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Va · phase 3 · Exelixis
Study of ST-1898 in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Cancer · phase 2 · Beijing Scitech-Mq Pharmaceuticals Limited

Trials reported · 6

ASTRA · phase 3 · 2019 · negative
DECISION · phase 3 · 2013 · positive
ESTIMABL2 · phase 3 · 2022 · positive
HiLo · phase 3 · 2012 · positive
IoN · phase 2/3 · 2025 · positive
SELECT · phase 3 · 2015 · positive

Open problems and what is being done

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.
What is being done about this
Resistance to treatment
Available now
CabozantinibApproved
In trials
A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid CarcinomaRecruiting
A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior VaActive
Study of ST-1898 in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid CancerRecruiting
Ideas and roadmaps
Nothing recorded yet.
Also on Nuclide: Open problems.
Multikinase inhibitors for RAI-refractory disease cause hypertension, weight loss, and fatigue; most patients need dose reductions and quality of life suffers.
What is being done about this
Resistance to treatment
Available now
CabozantinibApproved
In trials
A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid CarcinomaRecruiting
A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior VaActive
Study of ST-1898 in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid CancerRecruiting
Ideas and roadmaps
Nothing recorded yet.
Also on Nuclide: Open problems.
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.
What is being done about this
Resistance to treatment
Available now
CabozantinibApproved
In trials
A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid CarcinomaRecruiting
A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior VaActive
Study of ST-1898 in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid CancerRecruiting
Ideas and roadmaps
Nothing recorded yet.
Also on Nuclide: Open problems.
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.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Thyroid cancer

condition: Thyroid cancer

Open on ClinicalTrials.gov →

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