Thyroid cancer

Thyroid Cancer

A detailed Overview for Clinicians

Thyroid Cancer: A Clinical Overview for the Practicing Oncologist

Thyroid cancer occupies an unusual place in oncology. Most cases are curable, many patients live for decades after diagnosis, and yet a small subset of tumors are among the most lethal in all of medicine. For clinicians, that duality is the whole story: the challenge is rarely just treating the cancer; it's correctly sorting which cancer you're treating, and then matching the intensity of therapy to the biology in front of you rather than to the word "cancer" itself.

A Disease That Is Getting More Common — On Paper, At Least

Thyroid cancer is now the most frequently diagnosed endocrine malignancy worldwide. GLOBOCAN, which provides global estimates of cancer incidence, mortality and prevalence for over 185 countries and territories, estimated roughly 821,000 new cases and about 47,500 deaths globally in 2022, with incidence nearly three times higher in women than in men (Kuang et al., Chin Med J, 2024; PMID: 39261986).

In the United States alone, the American Cancer Society projected about 44,020 new cases and 2,290 deaths in 2025 — a ratio that, by itself, tells you something important about this disease: most people diagnosed with it will not die from it. That rising incidence, however, has not been matched by a rising mortality — a pattern most epidemiologists attribute largely to increased detection of small, indolent papillary cancers through incidental imaging and ultrasound, rather than to a true increase in aggressive disease (Pizzato et al., Lancet Diabetes Endocrinol, 2022; PMID: 35271818).

When talking to an anxious patient, it may be acceptable to explain that more diagnoses do not mean more danger.

Thyroid cancer is also, notably, a disease of relative youth compared with most solid tumors — the bulk of cases occur between ages 25 and 65 — and it affects women considerably more often than men.

Who Is at Risk

A few risk factors are worth asking about directly because they affect how closely you monitor someone and how you counsel their family.

The best-established case is a history of external radiation to the head and neck in infancy or childhood — historically given for benign conditions like an enlarged thymus, tonsils, adenoids, or even acne, and more recently understood through nuclear-fallout cohorts, including children exposed during the Chernobyl nuclear disaster on April 16, 1986.

The latency here is long and worth remembering: malignancies can appear as early as five years after exposure, or not surface for twenty years or more, which is exactly the kind of timeline that gets lost between a pediatric radiation history and an adult thyroid nodule unless someone asks about it directly.

Beyond radiation history, the risk factors worth screening for include a family history of thyroid disease or a multiple endocrine neoplasia (MEN) syndrome, a known RET pathogenic variant, a personal history of goiter, female sex, and, in some population-based data, Asian race.

None of these are reasons to biopsy an otherwise unremarkable nodule more aggressively on their own, but they're reasons to ask the question in the first place — particularly the family history and RET questions, since a positive answer opens the door to genetic counseling for the whole family, not just the patient in front of you.

How Patients Actually Present

Most patients don't come in because they feel sick. They come in because a nodule was felt on a routine exam, or — increasingly — flagged incidentally on a CT, MRI, or carotid ultrasound obtained for something else entirely. Thyroid function tests are usually normal in patients with thyroid cancer; TSH is a poor screening tool here, since it tells you about gland function, not malignant potential.

The diagnostic pathway that follows a suspicious nodule is well-worn: high-resolution neck ultrasound to characterize the nodule (margins, composition, calcifications, vascularity) and to survey the cervical lymph nodes, followed by ultrasound-guided fine-needle aspiration for nodules that meet size and sonographic risk criteria. For cytologically indeterminate nodules, molecular testing has become a genuinely useful adjunct, helping many patients avoid a diagnostic lobectomy they don't need.

This entire evaluation pathway, along with the risk-stratified sonographic patterns most labs and radiologists now use, was formalized in the American Thyroid Association's landmark 2015 management guidelines (Haugen et al., Thyroid, 2016; PMID: 26462967) — still the reference document most endocrinologists and surgeons work from a decade later.

The Histologic Subtypes, and Why They Matter So Much

Thyroid cancer isn't one disease, and the differences between subtypes matter more here than in almost any other tumor type. For clinical purposes, it's easiest to think of thyroid cancer as splitting into two lineages: cancers arising from the iodine-processing follicular cells (which range from well-differentiated papillary and follicular tumors, through poorly differentiated tumors, to the fully undifferentiated anaplastic carcinoma) and cancers arising from the calcitonin-producing parafollicular C-cells, which is medullary thyroid carcinoma alone. That distinction isn't academic — it's the reason radioactive iodine works in one disease but does nothing in the other.

Less commonly, the thyroid gland can also host lymphoma, sarcoma, or carcinosarcoma, or serve as a metastatic site for cancers originating elsewhere — lung, breast, and kidney primaries in particular — and these require an entirely different workup once suspected.

Papillary thyroid carcinoma accounts for the large majority of cases — commonly cited at 70–90% — and behaves, in most patients, like a chronic condition rather than an acute threat. It preferentially spreads to regional lymph nodes rather than to distant sites, and prognosis is excellent even when nodal disease is present at diagnosis.
Follicular thyroid carcinoma makes up a smaller share, roughly 10–15% of cases, and its natural history is different: it favors hematogenous spread to bone and lung rather than nodal involvement, which changes how these patients are surveilled and why a remnant lobe left behind after a lobectomy can quietly undermine radioiodine therapy later — the isotope will preferentially seek out normal residual tissue rather than the tumor.
Medullary thyroid carcinoma arises from the calcitonin-producing parafollicular C-cells rather than from follicular epithelium, and up to a quarter of cases occur as part of an inherited RET-mutation syndrome (MEN2A or MEN2B) rather than sporadically (Wirth et al., N Engl J Med, 2020; PMID: 32846061). This is the subtype in which a family history conversation and a germline testing referral genuinely change management for the patient's relatives, not just the patient.
Anaplastic thyroid carcinoma is rare — under 2% of cases — and sits at the opposite end of the spectrum from papillary disease entirely. It is one of the fastest-moving solid tumors in oncology, often presenting as a rapidly enlarging neck mass with airway compromise, and historically carried a median survival measured in months. This is the subtype in which a delayed diagnosis or a delayed molecular test can cost a patient the one window during which effective therapy is available.

Prognostic Factors: Age Still Dominates

Of everything that's been studied as a prognostic factor in differentiated thyroid cancer, age keeps coming out on top. Patients diagnosed under 40 do measurably better than older patients with otherwise comparable disease, and this isn't a subtle effect — one retrospective cohort using standard age/metastasis/extent/size risk criteria found a 98% twenty-year survival rate in the low-risk group versus 50% in the high-risk group.

Distant metastases at presentation and older age are consistently the two strongest predictors of poor outcome across multiple large series; other proposed factors, like the prognostic significance of regional lymph node involvement, have gone back and forth in the literature and remain unsettled.

Age matters enough to the field that it reshaped the staging system itself. A validation study of more than 9,000 patients found that 55, not 45, was the age cutoff that best separated risk groups — data substantial enough that the 8th edition of the AJCC Cancer Staging Manual moved the cutoff accordingly.

It's a good example of a staging system actually updating in response to outcomes data rather than tradition, and it's worth knowing the history if a patient or a trainee asks why the cutoff feels unusually specific.

Quick Reference: AJCC Staging for Papillary and Follicular Thyroid Cancer

Staging for well-differentiated thyroid cancer is unusual in that it runs on two different tracks depending on the patient's age at diagnosis.

Stage	Description
I	Tumor confined to the thyroid in patients ≥55 years; in patients <55 years, may include spread to nearby tissue and lymph nodes, but not distant sites.
II	Patients <55 years with distant metastases (the most advanced stage possible below 55); or patients ≥55 years with a tumor confined to, or with limited extension beyond, the thyroid, with or without nodal involvement, but no distant spread.
III	Patients ≥55 years only. Tumor extends into surrounding soft tissue, larynx, trachea, esophagus, or the recurrent laryngeal nerve; nodes may or may not be involved; no distant spread.
IVA	Patients ≥55 years only. Tumor extends into prevertebral fascia, or encases the carotid artery or mediastinal vessels; nodes may or may not be involved; no distant spread.
IVB	Patients ≥55 years only. Distant metastatic spread present — most often to lung or bone.

Papillary carcinoma is multifocal in up to half of cases, which is part of the rationale for total thyroidectomy discussed below. Hürthle cell carcinoma, a follicular variant, is staged and treated the same way as its non-Hürthle counterpart, though its prognosis runs slightly less favorably.

Surgery: Matching the Operation to the Tumor

The case for total thyroidectomy rests on two practical realities: multicentric involvement of both lobes is common, and any residual tumor left behind carries a small but real risk of dedifferentiating into a more aggressive, less treatable cell type over time.

An analysis of the National Cancer Data Base covering more than 52,000 patients treated surgically for papillary thyroid cancer found that extent of surgery made no difference in recurrence or survival for tumors under 1 cm, but for tumors 1 cm and larger, lobectomy alone carried a significantly higher risk of both recurrence and death than total thyroidectomy.

A separate pattern-of-care analysis spanning 1985 to 2003 showed the field moving in this direction over time — use of total thyroidectomy climbed from roughly 71% to 90% of cases over those two decades, with high-volume academic centers adopting the practice fastest.

That said, lobectomy still has a well-defined place. For a small, unifocal, intrathyroidal papillary carcinoma under 1 cm, without prior head and neck irradiation and without clinically or radiographically involved nodes, lobectomy alone is a reasonable and lower-morbidity option — accepting a modest 5–10% chance of an in-thyroid recurrence down the line.

When lymph nodes are clinically or radiographically suspicious, they're addressed at the time of initial surgery; a full radical neck dissection is not usually necessary, and while node removal reduces recurrence, it has not been shown to extend survival.

Radioactive Iodine: When It Helps, and When It's Just Extra Radiation

The rationale for postoperative radioactive iodine (RAI) is often poorly explained to patients, so it's worth restating plainly: RAI does two things. In higher-risk papillary and follicular cancers, therapeutic doses of 131-I have been shown to reduce recurrence. And separately, ablating any remaining normal thyroid tissue sharpens the diagnostic tools used afterward — serum thyroglobulin becomes a cleaner signal, and whole-body scanning becomes more interpretable, when there's no residual normal gland left to muddy the picture. That second benefit is really only realized with a near-total or total thyroidectomy; a meaningful thyroid remnant blunts thyroglobulin sensitivity and often forces repeat dosing.

The decision to give RAI is pathology-driven — primary tumor size, lymphovascular invasion, capsular invasion, and nodal burden all factor in — and it can be paired with either of two TSH-stimulation strategies: withdrawing thyroid hormone, or giving recombinant human TSH (rhTSH).

The evidence favors rhTSH on quality-of-life grounds; two separate phase III noninferiority trials found that low-dose and high-dose 131-I produced equivalent ablation rates (with complete ablation rates around 92% in one trial), and patients who underwent hormone withdrawal reported more hypothyroid symptoms and worse quality of life than those who received rhTSH. Neither trial, it's worth noting, was designed to answer the longer-term question of recurrence or survival, and neither settled whether RAI can be safely skipped altogether in the lowest-risk patients.

That last point matters clinically. For papillary microcarcinomas under 10 mm — genuinely very-low-risk disease with an excellent surgical prognosis on its own — adding 131-I has not been shown to improve outcomes. And in a 1,298-patient cohort from the French Thyroid Cancer Registry meeting ATA/European Thyroid Association low-risk criteria, RAI use made no measurable difference in overall or disease-free survival after more than a decade of follow-up. RAI is a tool for risk reduction in higher-risk disease, not a reflexive postoperative ritual for everyone who walks out of the OR without a thyroid.

Long-term, RAI isn't free of cost: second malignancies, sialadenitis, and lacrimal or salivary gland dysfunction are recognized late effects, which is part of why the field has moved toward giving the lowest effective dose in low-risk patients rather than defaulting to maximal ablation.

TSH Suppression

After thyroidectomy, essentially every patient except those who had a lobectomy needs thyroid hormone replacement — and for most, that replacement is deliberately supratherapeutic, suppressing TSH below the normal range, because TSH is a growth signal for any residual differentiated thyroid tissue.

How aggressively to suppress depends on recurrence risk and on what else is going on with the patient; a young, low-risk patient does not need the same suppression target as someone with high-risk residual disease, especially given the cardiac and bone-density costs of long-term subclinical hyperthyroidism.

The data support a progression-free survival benefit from suppression, but not a clearly demonstrated overall survival benefit — which is a nuance worth having ready when a patient asks why their TSH goal seems unusually low.

Medullary Thyroid Cancer Needs a Separate Playbook

Everything above about radioactive iodine applies only to follicular-cell-derived cancers. Medullary thyroid carcinoma, arising from the parafollicular C-cells, never takes up iodine at all — 131-I has no role in this disease at any stage — so it runs on its own diagnostic and therapeutic track from the start.

MTC accounts for only 3–4% of thyroid cancers but deserves outsized attention because roughly a quarter of cases are hereditary rather than sporadic, occurring as part of MEN2A, MEN2B, or a hereditary non-MEN syndrome.

Sporadic tumors tend to be unilateral; hereditary ones are almost always bilateral. Every patient with MTC — sporadic or hereditary in appearance — should be tested for a RET pathogenic variant, and a positive result should prompt cascade testing of family members, since calcitonin-based screening alone can yield false positives and genetic testing is the more reliable way to identify relatives who carry the variant.

Family members found to carry a pathogenic RET variant may choose prophylactic thyroidectomy at a young age, and patients with confirmed hereditary disease are also screened for the other tumors associated with MEN2 — pheochromocytoma and parathyroid hyperplasia — since missing a pheochromocytoma before neck surgery is a genuinely dangerous sequencing error. Serum calcitonin, secreted by nearly all MTC tumors, doubles as both a diagnostic marker and the most sensitive tool for tracking treatment response afterward.

Total thyroidectomy with central and often bilateral neck dissection is standard for localized disease — clinically palpable MTC carries microscopic nodal involvement more than 75% of the time — and when the tumor is confined to the gland, prognosis is genuinely excellent.

Overall survival across all MTC stages runs around 86% at five years and 65% at ten years, with the strongest prognostic factors being extent of disease at presentation, nodal involvement, and completeness of the surgical resection; advanced age, advanced stage, prior neck surgery, and MEN2B genotype all point toward a harder course.

For advanced or metastatic MTC, three systemic options now have phase III data, and they're distinct from the DTC drug sequence described below.

Vandetanib (ZD6474; Caprelsa®; Genzyme/Sanofi) in the placebo-controlled ZETA trial (NCT00410761) improved median PFS to an estimated 30.5 months versus 19.3 months on placebo, though QT prolongation is a real concern that limits its use in some patients (Wells et al., J Clin Oncol, 2012; PMID: 22025146).

Cabozantinib (Cabometyx® and Cometriq®; Exelixis), tested separately in MTC in the EXAM trial (NCT00704730; a different study from the COSMIC-311 trial (NCT03690388) discussed below, which enrolled DTC, not MTC), improved median PFS to 11.2 months versus 4.0 months on placebo, with a 28% objective response rate against 0% on placebo (Elisei et al., J Clin Oncol, 2013; PMID: 24002501).

Selpercatinib (Retevmo®; Eli Lilly and Company), in the RET-mutant MTC cohorts of the LIBRETTO-001 study (NCT03157128), produced response rates of 73% in kinase-inhibitor-naive patients and 69% in patients previously treated with vandetanib or cabozantinib — with the vast majority of responses still ongoing at one year (Wirth et al., N Engl J Med, 2020; PMID: 32846061).

Given that selectivity advantage, RET testing at the time of an advanced MTC diagnosis determines whether a patient is matched to selpercatinib first, rather than starting with a multikinase inhibitor.

When Radioiodine Stops Working

Roughly a quarter of recurrences and metastases from well-differentiated thyroid cancer simply won't take up iodine, and this is where the field has changed the most in the last fifteen years. Before targeted therapy, iodine-refractory disease meant thyroid hormone suppression, watching, and not much else beyond palliative surgery or radiation for isolated lesions.

That changed with three sequential phase 3 trials of multitargeted tyrosine kinase inhibitors.

Sorafenib (Nexavar®; Bayer) tested in the DECISION trial (NCT00984282) against placebo in 417 patients with progressive, RAI-refractory differentiated thyroid cancer, nearly doubled median progression-free survival — 10.8 months versus 5.8 months — though at a real toxicity cost: hand-foot skin reactions, diarrhea, and alopecia were common, and seven patients developed cutaneous squamous cell carcinomas on treatment (Brose et al., Lancet, 2014; PMID: 24768112).

Lenvatinib (Lenvima®; Eisai), in the SELECT trial (NCT01321554), went further still: median PFS of 18.3 months versus 3.6 months on placebo, with an objective response rate of nearly 65% compared with 1.5% — one of the larger effect sizes seen in any solid-tumor trial of its era — though adverse events occurred in essentially all treated patients and included hypertension, diarrhea, and significant weight loss (Schlumberger et al., N Engl J Med, 2015; PMID: 25671254).

Cabozantinib (Cabometyx® and Cometriq®; Exelixis), evaluated in COSMIC-311 specifically in patients who had already progressed on lenvatinib and/or sorafenib, confirmed there's still meaningful benefit available in the second line: median PFS was not reached in the cabozantinib arm versus 1.9 months on placebo, a hazard ratio of 0.22 (Brose et al., Lancet Oncol, 2021; PMID: 34237250).

The practical importance for clinicians is that these three drugs now form a genuine sequence rather than a single last resort, and toxicity management — dose interruptions, dose reductions, proactive counseling on skin and GI effects — is as much a part of using them well as the prescription itself.

Biomarker-Driven Therapy: Where the Real Progress Has Happened

The most meaningful shift in thyroid cancer care over the last several years hasn't been in surgical technique — it's the arrival of genuinely selective, biomarker-matched therapy for the patients who don't fit the "watch and reassure" mold, and increasingly, genomic testing for RET and NTRK alterations is recommended for anyone with advanced, progressive disease.

RET-altered disease. Selpercatinib (Retevmo®; Eli Lilly and Company), a highly selective RET kinase inhibitor, has changed the calculus for both RET-mutant medullary thyroid cancer and RET fusion-positive differentiated thyroid cancer. In the phase 1/2 LIBRETTO-001 trial, selpercatinib produced an objective response rate of 79% in RET fusion–positive thyroid cancer patients who had already had at least one prior systemic therapy, with 71% of responses still ongoing at one year (Wirth et al., N Engl J Med, 2020; PMID: 32846061).

The subsequent phase 3 LIBRETTO-531 trial (NCT04211337) moved this into the first-line, kinase-inhibitor-naive setting for medullary thyroid cancer, comparing selpercatinib directly against physician's choice of cabozantinib or vandetanib: median PFS was not reached with selpercatinib versus 16.8 months with standard therapy, and the overall response rate was 69.4% versus 38.8% — with far fewer patients needing a dose reduction or stopping treatment altogether (Hadoux et al., N Engl J Med, 2023; PMID: 37870969).

For a subtype long treated with poorly tolerated multikinase inhibitors, that safety margin is not a footnote — it's the difference between a patient staying on effective therapy or coming off it. Pralsetinib, a second RET-selective inhibitor, showed comparably strong activity in the ARROW trial, though it was voluntarily withdrawn from its FDA-approved thyroid cancer indication in 2023.

NTRK-fusion disease. This is rare in thyroid cancer, but worth knowing about because the response rates in the patients who do carry an NTRK fusion are striking. In a pooled analysis of larotrectinib across TRK fusion–positive cancers, the 24 patients with thyroid cancer specifically had a 79% objective response rate.

Entrectinib (Rozlytrek®; Genentech/Roche) a related TRK/ROS1/ALK inhibitor, showed a more modest 20% response rate in the small number of thyroid cancer patients in its pooled analysis — a reminder that these are agnostic, biomarker-defined therapies whose activity can vary somewhat by tumor type even within the same fusion category.

BRAF V600E-mutant anaplastic thyroid cancer. It's worth pausing on what treatment for this disease looked like before targeted therapy existed, because it puts the breakthrough in context. Anaplastic thyroid cancer typically presents as a hard, rapidly growing neck mass that has often already invaded surrounding structures by the time of diagnosis, frequently requiring a tracheostomy just to secure the airway; it does not respond to radioactive iodine at all. Surgery is rarely an option beyond debulking for symptom control, and conventional cytotoxic therapy has modest activity at best — single-agent doxorubicin produces partial remissions in roughly 30% of patients, and adding cisplatin further improves that, but responses are typically measured in weeks. Against that backdrop, the arrival of BRAF-targeted therapy is arguably the most dramatic turnaround story in thyroid oncology. Estimates of how many anaplastic thyroid cancers carry a BRAF V600E mutation vary somewhat across series, from roughly a quarter to a third of cases, and the combination of dabrafenib (Tafinlar®; Novartis; a BRAF inhibitor) plus trametinib (Mekinist®; Novartis; a MEK inhibitor) produced a confirmed overall response rate of 69% in the pivotal ROAR basket study cohort — a result essentially unheard of in a disease with no prior systemic therapy of meaningful benefit (Subbiah et al., J Clin Oncol, 2018; PMID: 29072975). An extended follow-up of the full 36-patient ROAR cohort confirmed durable clinical benefit years later (Subbiah et al., Ann Oncol, 2022; PMID: 35026411). The practical implication for every oncologist reading this: BRAF V600E testing should now be considered mandatory at the time of diagnosis of anaplastic thyroid cancer, ideally with same-day or next-day results, because the therapeutic window in this disease is measured in weeks, not months.

Recurrent Disease

Even with excellent initial treatment, roughly 10–30% of patients thought to be disease-free will recur — about 80% of those recurrences remain confined to the neck, and 20% present as distant metastases, most often in the lungs. Prognosis after a clinically detectable recurrence is generally worse than for disease first picked up only on a follow-up 131-I scan, which is part of the argument for the structured, risk-based surveillance (physical exam, serial thyroglobulin, imaging) that most patients are placed on after initial treatment.

For operable recurrences, repeat surgery — with or without additional RAI — remains genuinely worthwhile: roughly half of patients who undergo a second operation for recurrent disease can be rendered disease-free again.

For patients whose recurrence doesn't take up iodine, the sequence of targeted therapies above becomes the relevant pathway, and enrollment in a clinical trial is always worth raising, particularly for patients whose tumors carry an actionable RET or NTRK alteration that hasn't yet been matched to therapy.

The Takeaway for Clinical Practice

Thyroid cancer rewards precision more than aggression. The right ultrasound risk-stratification and biopsy criteria keep patients with indolent disease out of unnecessary operating rooms. The right extent of surgery, matched to tumor size, multifocality, and age, measurably changes recurrence and survival.

RAI and TSH suppression are tools to be dosed to risk, not applied reflexively — and for medullary disease, RAI is never the answer at all, which makes the RET-testing conversation happen earlier rather than later.

The right molecular workup — RET status, NTRK status, BRAF status — increasingly determines whether a patient with iodine-refractory, medullary, or anaplastic disease has access to a therapy that yields a real, durable response rather than a marginal one. It's worth every practicing oncologist's time to recheck their working assumptions against where this data now stands.

Select Clinical Trias

An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer - ClinicalTrials.gov ID NCT00410761
A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy - ClinicalTrials.gov ID NCT0369038
Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) - ClinicalTrials.gov ID NCT00704730
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001) - ClinicalTrials.gov ID NCT03157128
Nexavar® Versus Placebo in Locally Advanced/Metastatic RAI-Refractory Differentiated Thyroid Cancer - ClinicalTrials.gov ID NCT00984282
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC) (SELECT) - ClinicalTrials.gov ID NCT01321554
A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531) - ClinicalTrials.gov ID NCT04211337

Highlights of Prescribing Information

Vandetanib (ZD6474; Caprelsa®; Genzyme/Sanofi)[Prescribing Information]
Cabozantinib (Cabometyx® and Cometriq®; Exelixis)[Prescribing information]
Selpercatinib (Retevmo®; Eli Lilly and Company)[Prescribing Information]
Sorafenib (Nexavar®; Bayer)[Precscribing Information]
Lenvatinib (Lenvima®; Eisai)[Prescribing information]
Pralsetinib (Gavreto®; Rigel Pharmaceuticals [Prescribing Information]
Dabrafenib (Tafinlar®; Novartis)[Prescribing Information]
Trametinib (Mekinist®; Novartis)[Prescribing Information]
Entrectinib (Rozlytrek®; Genentech/Roche)[Prescribing Information]

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[13] Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J, Worden F, Brose M, Patel J, Leboulleux S, Godbert Y, Barlesi F, Morris JC, Owonikoko TK, Tan DSW, Gautschi O, Weiss J, de la Fouchardière C, Burkard ME, Laskin J, Taylor MH, Kroiss M, Medioni J, Goldman JW, Bauer TM, Levy B, Zhu VW, Lakhani N, Moreno V, Ebata K, Nguyen M, Heirich D, Zhu EY, Huang X, Yang L, Kherani J, Rothenberg SM, Drilon A, Subbiah V, Shah MH, Cabanillas ME. Efficacy of Selpercatinib in RET-Altered Thyroid Cancers. N Engl J Med. 2020 Aug 27;383(9):825-835. doi: 10.1056/NEJMoa2005651. PMID: 32846061; PMCID: PMC10777663.

[14] Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012 Jan 10;30(2):134-41. doi: 10.1200/JCO.2011.35.5040. Epub 2011 Oct 24. Erratum in: J Clin Oncol. 2013 Aug 20;31(24):3049. PMID: 22025146; PMCID: PMC3675689.

[15] Elisei R, Schlumberger MJ, Müller SP, Schöffski P, Brose MS, Shah MH, Licitra L, Jarzab B, Medvedev V, Kreissl MC, Niederle B, Cohen EE, Wirth LJ, Ali H, Hessel C, Yaron Y, Ball D, Nelkin B, Sherman SI. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013 Oct 10;31(29):3639-46. doi: 10.1200/JCO.2012.48.4659. Epub 2013 Sep 3. Erratum in: J Clin Oncol. 2014 Jun 10;32(17):1864. PMID: 24002501; PMCID: PMC4164813.

[16] Hadoux J, Elisei R, Brose MS, Hoff AO, Robinson BG, Gao M, Jarzab B, Isaev P, Kopeckova K, Wadsley J, Führer D, Keam B, Bardet S, Sherman EJ, Tahara M, Hu MI, Singh R, Lin Y, Soldatenkova V, Wright J, Lin B, Maeda P, Capdevila J, Wirth LJ; LIBRETTO-531 Trial Investigators. Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. N Engl J Med. 2023 Nov 16;389(20):1851-1861. doi: 10.1056/NEJMoa2309719. Epub 2023 Oct 21. PMID: 37870969.

[17] Subbiah V, Hu MI, Wirth LJ, Schuler M, Mansfield AS, Curigliano G, Brose MS, Zhu VW, Leboulleux S, Bowles DW, Baik CS, Adkins D, Keam B, Matos I, Garralda E, Gainor JF, Lopes G, Lin CC, Godbert Y, Sarker D, Miller SG, Clifford C, Zhang H, Turner CD, Taylor MH. Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study. Lancet Diabetes Endocrinol. 2021 Aug;9(8):491-501. doi: 10.1016/S2213-8587(21)00120-0. Epub 2021 Jun 9. Erratum in: Lancet Diabetes Endocrinol. 2021 Oct;9(10):e4. doi: 10.1016/S2213-8587(21)00247-3. PMID: 34118198; PMCID: PMC13224057.

[18] Hong DS, DuBois SG, Kummar S, Farago AF, Albert CM, Rohrberg KS, van Tilburg CM, Nagasubramanian R, Berlin JD, Federman N, Mascarenhas L, Geoerger B, Dowlati A, Pappo AS, Bielack S, Doz F, McDermott R, Patel JD, Schilder RJ, Tahara M, Pfister SM, Witt O, Ladanyi M, Rudzinski ER, Nanda S, Childs BH, Laetsch TW, Hyman DM, Drilon A. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020 Apr;21(4):531-540. doi: 10.1016/S1470-2045(19)30856-3. Epub 2020 Feb 24. PMID: 32105622; PMCID: PMC7497841.

[19] Doebele RC, Drilon A, Paz-Ares L, Siena S, Shaw AT, Farago AF, Blakely CM, Seto T, Cho BC, Tosi D, Besse B, Chawla SP, Bazhenova L, Krauss JC, Chae YK, Barve M, Garrido-Laguna I, Liu SV, Conkling P, John T, Fakih M, Sigal D, Loong HH, Buchschacher GL Jr, Garrido P, Nieva J, Steuer C, Overbeck TR, Bowles DW, Fox E, Riehl T, Chow-Maneval E, Simmons B, Cui N, Johnson A, Eng S, Wilson TR, Demetri GD; trial investigators. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020 Feb;21(2):271-282. doi: 10.1016/S1470-2045(19)30691-6. Epub 2019 Dec 11. Erratum in: Lancet Oncol. 2020 Feb;21(2):e70. doi: 10.1016/S1470-2045(20)30029-2. Erratum in: Lancet Oncol. 2020 Jul;21(7):e341. doi: 10.1016/S1470-2045(20)30345-4. Erratum in: Lancet Oncol. 2020 Aug;21(8):e372. doi: 10.1016/S1470-2045(20)30382-X. Erratum in: Lancet Oncol. 2021 Oct;22(10):e428. doi: 10.1016/S1470-2045(21)00538-6. PMID: 31838007; PMCID: PMC7461630.

[20] Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, Wen PY, Zielinski C, Cabanillas ME, Urbanowitz G, Mookerjee B, Wang D, Rangwala F, Keam B. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol. 2018 Jan 1;36(1):7-13. doi: 10.1200/JCO.2017.73.6785. Epub 2017 Oct 26. PMID: 29072975; PMCID: PMC5791845.

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Prepared for Onco'Zine. Sources include peer-reviewed literature indexed in PubMed and the NCI PDQ Thyroid Cancer Treatment summary; all statistics and trial data are attributed to their original publications above. Last update: September 1, 2026.

A Guide for Patients

What Patients Should Know

A patient information companion to the clinical overview above. Hearing the word cancer is frightening no matter what comes after it. If what comes after it is "thyroid," there's something worth saying right away, gently but honestly: thyroid cancer is one of the more treatable cancers a person can be diagnosed with.

That doesn't make the diagnosis any less real or any less worth taking seriously — but it does mean that for most people, this is a condition to be managed and moved past, not a crisis without an end in sight.

What Is the Thyroid, and What Does It Do?

The thyroid is a small, butterfly-shaped gland sitting low in the front of your neck, just above where your collarbones meet. Despite its size, it does a lot of work — it makes hormones that help set the pace for your metabolism, your heart rate, your body temperature, and your energy levels. When a cancer forms in this gland, it doesn't usually change how the gland functions day to day, which is part of why it can be so easy to miss at first.

How Thyroid Cancer Is Usually Diagnosed

Most people don't feel sick. The most common first sign is a small, painless lump — called a thyroid nodule — that you or your doctor notices in your neck. Sometimes it's found completely by accident, on a scan done for something unrelated.

Try not to let that word "lump" set off alarm bells on its own. The large majority of thyroid nodules are not cancer — most estimates put the number at somewhere around one in ten. If your doctor does find a nodule, the usual next steps are an ultrasound to get a closer look at it and, if it still looks like it needs a closer look, a simple needle biopsy done in the office. Occasionally, blood tests and additional imaging are used alongside these to complete the picture.

Some people do notice symptoms, especially if the nodule has grown larger. These can include neck swelling, a hoarse voice, or difficulty swallowing or breathing. If you notice any of these, it's worth having them checked, though they're often caused by something other than cancer.

Why Does This Happen?

Like other cancers, thyroid cancer starts when changes occur in the DNA of a thyroid cell, causing it to grow and divide when it shouldn't. Most of the time, these changes happen over the course of a person's life for reasons that aren't fully understood. In some families, though, a tendency toward thyroid cancer is inherited — passed down through genes from a parent.

A few things are known to raise the likelihood of developing thyroid cancer:

Radiation exposure to the head or neck, especially during childhood. This was more common decades ago, when radiation was sometimes used to treat benign childhood conditions.
A family history of thyroid cancer, or of an inherited condition such as multiple endocrine neoplasia (MEN2A or MEN2B).
Being female. Thyroid cancer is diagnosed roughly three times more often in women than in men, most often in a woman's 40s or 50s; in men, it tends to show up somewhat later, in the 60s or 70s.
A personal history of goiter (an enlarged thyroid) or low dietary iodine.

Having one or more of these doesn't mean you'll develop thyroid cancer — it simply means it's worth mentioning to your doctor, particularly a family history of thyroid disease, since that can sometimes prompt a conversation about genetic testing for you and your relatives.

The Different Types, in Plain Terms

Not all thyroid cancers behave the same way, and your doctor will tailor your care to the specific type you have. Broadly:

Papillary thyroid cancer is by far the most common type — it accounts for the large majority of cases. It tends to grow slowly, and even when it spreads to lymph nodes in the neck, it usually responds very well to treatment.
Follicular thyroid cancer is less common. It's somewhat more likely to spread further afield, to the lungs or bones, which can make it a little more involved to treat if that happens.
Medullary thyroid cancer is less common still, and it behaves differently from the two types above — about a quarter of the time, it runs in families, tied to a specific inherited gene change. If you're diagnosed with this type, genetic counseling for you and close relatives is usually recommended.
Anaplastic thyroid cancer is rare, but it's the most aggressive form, growing and spreading quickly. It's also the one where doctors move fastest, because early, decisive treatment matters the most here.

If your pathology report uses a term you don't recognize, it's always fair to ask your doctor to walk through exactly what it means for your specific situation — the differences between these types genuinely change what treatment looks like.

How Thyroid Cancer Is Staged

Like most cancers, thyroid cancer is assigned a stage, from I through IV, based on the size of the tumor and how far it has spread. A higher number generally means a larger tumor or more spread — first to nearby lymph nodes, and, less often, to more distant parts of the body such as the lungs or bones.

One quirk worth knowing about: for the more common thyroid cancer types, your age at diagnosis actually factors into your stage, alongside the size and spread of the tumor. This can feel confusing when you're comparing notes with someone else who had a "different stage" with what sounds like a similar tumor — your care team is the best resource for explaining exactly what your particular stage means for you.

How Thyroid Cancer Is Treated

Surgery is the starting point for almost everyone. Depending on the size and extent of the cancer, your surgeon may remove the entire thyroid gland (a thyroidectomy) or just the affected half (a lobectomy), along with any lymph nodes that show signs of cancer.

Depending on your situation, one or more additional treatments may follow:

Radioactive iodine therapy. Thyroid tissue is unusually good at absorbing iodine, and this treatment takes advantage of that: you swallow a pill or liquid containing a radioactive form of iodine, which travels to and destroys any remaining thyroid tissue or thyroid cancer cells, largely sparing the rest of the body. This only works for cancers that still take up iodine — not all types do.
External radiation therapy. For cancers that don't absorb iodine, or in certain other situations, radiation can instead be delivered from a machine outside the body.
Thyroid hormone therapy. After surgery, you'll need to take a thyroid hormone replacement pill, since your body can no longer make enough on its own. At a higher dose, this same medication also helps suppress any signal that might encourage leftover thyroid cells to grow, which is part of why the dose is often higher than a simple replacement dose.
Targeted therapy. For more advanced or harder-to-treat cancers, especially those that no longer respond to radioactive iodine, newer medications exist that are designed to home in on specific changes inside cancer cells. These have meaningfully improved outcomes for people who once had few options.
Chemotherapy. This is used only rarely in thyroid cancer, generally reserved for aggressive cancer that isn't responding to other treatments.
Clinical trials. If standard treatments aren't working well enough for your situation, a clinical trial may offer access to newer approaches. It's always reasonable to ask your care team whether one might be a fit for you.

Most people who have surgery or radiation involving the thyroid will need to take thyroid hormone replacement for the rest of their life. This isn't a sign that anything has gone wrong — it's simply replacing a hormone your body used to make on its own, and it's very manageable with regular blood tests and dose adjustments.

What Happens After Treatment

You'll have regular follow-up visits — with physical exams, blood tests, and sometimes imaging or ultrasound — to make sure the cancer hasn't returned. Recurrence is possible but not the norm, particularly with the more common thyroid cancer types.

If the cancer recurs, it's most often caught through routine blood work rather than through new symptoms, which is exactly why those follow-up appointments matter even once you're feeling completely well.

If you do notice new swelling in your neck or enlarged lymph nodes between visits, it's worth calling your care team rather than waiting for your next scheduled appointment.

General Outlook

This is the part worth sitting with for a moment: for most people with thyroid cancer, the long-term outlook is genuinely excellent. Across all types combined, the overall survival rate is very high, and for the most common types — papillary and follicular — that holds true even when the cancer has spread to nearby lymph nodes.

That said, the outlook does vary by type and by how advanced the cancer is at diagnosis. Medullary thyroid cancer carries a more serious prognosis once it's advanced, and anaplastic thyroid cancer, being rare and fast-moving, is the most serious diagnosis in this family of cancers. Your own outlook depends on your specific diagnosis, and your doctor is the right person to walk you through what your particular numbers mean — statistics describe groups of people, not any one individual's story.

If Thyroid Cancer Runs in Your Family

If you know thyroid cancer runs in your family, or if a close relative has been diagnosed with medullary thyroid cancer specifically, it's worth raising this with your doctor.

A genetic test can sometimes identify an inherited gene change before any cancer develops, which opens the door to closer monitoring — or, in some cases, a preventive conversation about early treatment — well before anything shows up on a scan.

If you or a family member has ever been exposed to radioactive fallout, from a nuclear accident or otherwise, a medication called potassium iodide, taken within about a day of exposure, can help protect the thyroid by preventing it from absorbing radioactive iodine from the environment. This is a preventive measure tied to a specific kind of exposure, not a treatment for existing thyroid cancer.

Thyroid Cancer and Pregnancy

Thyroid cancer is one of the more common cancers diagnosed during pregnancy. If you're pregnant at the time of diagnosis, your care team will weigh the specifics of your case carefully — sometimes treatment can safely wait until after delivery, and when surgery can't wait, it's generally considered safe to perform during pregnancy.

Treatments involving radiation are usually postponed until after you've finished breastfeeding. This is, however, a conversation worth having directly and early with your obstetric and oncology teams together.

Questions Worth Asking Your Care Team

It can be hard to think of everything in the moment, so it may help to bring a written list to your appointments. A few starting points:

What type of thyroid cancer do I have, and what stage is it?
What treatment do you recommend, and why this approach over the alternatives?
Will I need radioactive iodine, and if so, what should I expect from it?
Will I need to take thyroid hormone for the rest of my life, and what will monitoring that look like?
Should my family members be tested or screened, given my diagnosis?
What does my long-term follow-up schedule look like?

A cancer diagnosis is a lot to absorb in one sitting, and it's completely reasonable to need things repeated or explained more than once. For thyroid cancer in particular, the path forward for most people is genuinely hopeful — and a good care team will make sure you understand every step of it.

This information is intended to help you understand and discuss your diagnosis with your healthcare provider. It is not a substitute for personalized medical advice from your own care team.

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