Medullary thyroid cancer
Medullary thyroid cancer comes from the calcitonin-making C cells, not the thyroid hormone cells, so radioactive iodine does not work. Surgery is the only cure, a quarter of cases run in families through the RET gene, and the RET-selective drug selpercatinib has transformed treatment of advanced disease.
Overview
Medullary thyroid cancer arises from the parafollicular C cells and secretes calcitonin, which serves as its tumour marker. Germline RET mutations cause the hereditary forms (MEN2A, MEN2B and familial medullary thyroid cancer), and children who inherit them have the thyroid removed before cancer develops, timed by the mutation's risk level; most sporadic tumours carry a somatic RET M918T mutation, and a minority RAS mutations. Total thyroidectomy with central neck dissection is the only curative treatment, and calcitonin doubling time guides follow-up. For progressive advanced disease, vandetanib (2011) and cabozantinib (2012) were the first approved kinase inhibitors; selpercatinib, a RET-selective inhibitor, beat them in the LIBRETTO-531 trial and is now the standard for RET-mutant disease, with pralsetinib as an alternative. Phaeochromocytoma must be excluded before any thyroid surgery in MEN2.
State of the art
- Selpercatinib gave a response rate near 70 percent and much longer progression-free survival than the older multikinase drugs, with fewer side effects.
- Genetic testing and prophylactic surgery have made hereditary medullary cancer a preventable disease in tested families.
- Calcitonin doubling time is one of the most reliable prognostic tools in any cancer.
Anatomy and lymph node drainage
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.
- Oral cavity and tongue
- Oropharynx: tonsil, base of tongue (HPV)
- Nasopharynx (EBV)
- Larynx and hypopharynx
- Parotid and other salivary glands
- ThyroidHereditary: MEN2A (with phaeochromocytoma and hyperparathyroidism) · Hereditary: MEN2B (mucosal neuromas, marfanoid habitus, early aggressive disease) · Familial medullary thyroid cancer only
- level I (submandibular)
- level II (upper jugular)
- level III-IV (jugular)
- level V (posterior)
- level VI (central, thyroid)
- retropharyngeal (nasopharynx)
Same organ: Oropharyngeal cancer (tonsil and base of tongue), Laryngeal and hypopharyngeal cancer, Oral cavity cancer (mouth and tongue), Head and neck squamous cell carcinoma, Nasopharyngeal carcinoma, Salivary gland cancers, Papillary thyroid cancer, Follicular thyroid cancer, Anaplastic thyroid cancer, Thyroid cancer, Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma), NUT carcinoma (midline carcinoma with NUTM1 rearrangement), Parathyroid carcinoma, Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)
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.
- Two to four percent of thyroid cancers; a quarter are inherited through a RET mutation in the multiple endocrine neoplasia type 2 syndromes; ten-year survival ranges from above 95 percent for disease confined to the thyroid to under half once distant spread has occurred.
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
Prophylactic total thyroidectomy in childhood, timed by the RET codon risk category (before age one in MEN2B).
Total thyroidectomy with central compartment dissection, lateral dissection when nodes are involved; no radioactive iodine; levothyroxine replacement only.
Selpercatinib first line (LIBRETTO-531 beat cabozantinib and vandetanib); pralsetinib as an alternative.
Cabozantinib or vandetanib; external radiotherapy for local control; somatostatin analogues for diarrhoea from calcitonin.
Subtypes & biomarkers
top- Sporadic (about 75 percent)
- Hereditary : MEN2A (with phaeochromocytoma and hyperparathyroidism)
- Hereditary : MEN2B (mucosal neuromas, marfanoid habitus, early aggressive disease)
- Familial medullary thyroid cancer only
- Calcitonin and CEA (diagnosis, follow-up and doubling time)
- Germline RET testing in every patient
- Somatic RET M918T
- RAS mutations in RET-negative tumours
How often this target appears
- 1959Hazard describes medullary thyroid carcinoma as a distinct tumour
- 1993RET mutations found to cause MEN2
- 2011Vandetanib approved
- 2012Cabozantinib approved (EXAM trial)
- 2020Selpercatinib approved for RET-mutant disease
- 2023LIBRETTO-531: selpercatinib beats the multikinase drugs first line
What is in development for Medullary thyroid cancer, drawn from the whole corpus: 0 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.
Nothing recorded in development for this cancer yet.
Open problems and what is being done
No cure once the disease has spread beyond the neck.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- Bone-modifying agents (bisphosphonates, denosumab)Standard of care
- DordaviproneApproved
- HIPEC / PIPAC (intraperitoneal chemotherapy)Established
- Laser interstitial thermal therapy (LITT)Established
- Liquid biopsy (ctDNA)Standard of care
- Lutetium-177 vipivotide tetraxetanApproved
In trials- ACTIONRecruiting
- CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)Phase 1
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
- DESTINY-Breast12Positive
- DYNAMICPositive
- EF-14Positive
Ideas and roadmaps- A billion-dollar prize for the first durable cure of a lethal metastatic cancer
- A blood test for the pre-metastatic niche
- A global rapid tissue donation network for metastatic disease
- A national rapid research autopsy network for end-stage cancer
- A regulatory endpoint for drugs that block spread, not tumours
- A ring-fenced metastasis programme with metastasis-specific endpoints
Background: Blood-brain barrier (BBB), Circulating tumour DNA (ctDNA), EGFRvIII, Epithelial-mesenchymal transition & drug efflux, H3 K27M (diffuse midline glioma). Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
Resistance mutations to RET inhibitors (G810) are emerging.
and how the field plans to fix it →What is being done about thisResistance to treatmentAvailable now- CabozantinibApproved
- AmivantamabApproved
- CamizestrantApproved
- Comprehensive genomic profilingStandard of care
- Liquid biopsy (ctDNA)Standard of care
- LorlatinibApproved
In trials- ADC payload neutralisersPhase 1
- BGB-16673Phase 3
- Bispecific ADCPhase 3
- BRUIN CLL-321Positive
- CaDAnCe-304Recruiting
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
Ideas and roadmaps- A clone report from blood at every treatment cycle
- A fast route to the matched drug when it is licensed for another cancer
- A multi-cancer platform trial of adaptive (dose-holiday) therapy
- A national rapid research autopsy network for end-stage cancer
- A standard evolvability score for every tumour
- A standing platform trial that assigns treatment by how the tumour escaped
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance atlas · Lines of therapy.
RET-negative sporadic disease has no targeted option.
and how the field plans to fix it →What is being done about thisCancers without a drug targetAvailable now- AdagrasibApproved
- CRISPR functional genomicsEstablished
- DaraxonrasibApproved
- KRAS & RAS inhibitorsApproved
- PROTACs & molecular glues (targeted protein degradation)Approved
- RevumenibApproved
In trials- AI-driven drug & target discoveryPhase 2
- CodeBreaK 200Positive
- ELI-002 7PPhase 2
- ElironrasibPhase 2
- KRYSTAL-12Positive
- MRTX1133Phase 1
Ideas and roadmaps- A drug screen that only rewards killing sleeping cancer cells
- A guaranteed purchase prize for the first drug against a named hard target
- A precompetitive consortium for the twenty hardest cancer targets
- A synthetic lethality map for every cancer driver in every tissue context
- A target de-risking index that counts failures as well as successes
- AI-designed proteins that grip the floppy parts of cancer drivers
Background: p53 / RB / cell-cycle checkpoint, RAS / RAF / MEK / ERK (MAPK). Also on OnCo: Targets · KRAS roadmap.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Expert centres
topExpert centres
- via Thyroid cancer
- via Thyroid cancer
- via Thyroid cancer
- ASST Spedali Civili di BresciaBrescia, ITvia Thyroid cancer
- Cancer Research UKLondon, GBvia Thyroid cancer
- First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou, CNvia Thyroid cancer
- via Thyroid cancer
- Kyushu University HospitalFukuoka, JPvia RET
- National Cancer Center Hospital EastKashiwa, Chiba, JPvia RET
- National Cancer Center KoreaGoyang, KRvia Thyroid cancer
- Peking Union Medical College HospitalBeijing, CNvia Thyroid cancer
- Shanghai Chest HospitalShanghai, CNvia RET
- Tawam HospitalAl Ain, AEvia Thyroid cancer
Questions to ask
topQuestions to ask your oncologist about Medullary thyroid cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Calcitonin and CEA, Germline RET testing in every patient, Somatic RET M918T, RAS mutations in RET-negative tumours), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Sporadic, Hereditary: MEN2A, Hereditary: MEN2B.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Hereditary RET carriers
- For my situation (hereditary ret carriers), which of the standard options do you recommend and why?Why: Guideline options include: Prophylactic total thyroidectomy in childhood, timed by the RET codon risk category (before age one in MEN2B).
Localised disease
- For my situation (localised disease), which of the standard options do you recommend and why?Why: Guideline options include: Total thyroidectomy with central compartment dissection, lateral dissection when nodes are involved; no radioactive iodine; levothyroxine replacement only.
Advanced RET-mutant disease
- For my situation (advanced ret-mutant disease), which of the standard options do you recommend and why?Why: Guideline options include: Selpercatinib first line (LIBRETTO-531 beat cabozantinib and vandetanib); pralsetinib as an alternative.
- Am I a candidate for Selpercatinib, Pralsetinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Advanced RET-negative disease
- For my situation (advanced ret-negative disease), which of the standard options do you recommend and why?Why: Guideline options include: Cabozantinib or vandetanib; external radiotherapy for local control; somatostatin analogues for diarrhoea from calcitonin.
- Am I a candidate for Cabozantinib, Vandetanib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “No cure once the disease has spread beyond the neck”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Resistance mutations to RET inhibitors (G810) are emerging”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
2targets
4drugs
4companies
4Latest papers
topQuery for this cancer: (TITLE:"Medullary thyroid cancer" OR ABSTRACT:"Medullary thyroid cancer" OR TITLE:"Medullary thyroid carcinoma" OR ABSTRACT:"Medullary thyroid carcinoma" OR TITLE:"MTC" OR ABSTRACT:"MTC") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Medullary thyroid cancer, not a curated reading list.
Similar pages
not linked directly; found by shared links- CancerPapillary thyroid cancer
Shares Selpercatinib, Thyroid cancer and the tag subtype-page.
- CancerChromophobe renal cell carcinoma
Shares Cabozantinib and the tag subtype-page.
- CancerPapillary renal cell carcinoma
Shares Cabozantinib and the tag subtype-page.
- CancerFollicular thyroid cancer
Shares Thyroid cancer and the tag subtype-page.
- CancerAnaplastic thyroid cancer
Shares Thyroid cancer and the tag subtype-page.
- CancerClear cell renal cell carcinoma
Shares Cabozantinib and the tag subtype-page.
- TrialLIBRETTO-531
Shares Vandetanib, Selpercatinib, Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4), RET.
- TrialARROW (thyroid cohorts)
Shares Pralsetinib, RET, Thyroid cancer.