NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma Version 2.2026

Full title: NCCN Guidelines Thyroid Carcinoma V2.2026, National Comprehensive Cancer Network, updated June 2, 2026 Core positioning: Multidisciplinary algorithmic guideline covering thyroid nodule evaluation, differentiated thyroid carcinoma (DTC: papillary, follicular, oncocytic), medullary thyroid carcinoma (MTC), anaplastic thyroid carcinoma (ATC). Major updates in V2.2026 refine RET mutation risk stratification for MTC; clarify active surveillance (AS) eligibility only for low-risk papillary microcarcinoma (cT1aN0M0); follicular/oncocytic neoplasms (any size) no longer qualify for active surveillance; molecular testing integrated into Bethesda III/IV triage. Cross-reference NASIT 2026 low-risk PTA ablation statement.

1. Thyroid Nodule Initial Evaluation & FNA Triage

1. Baseline: Neck ultrasound + TSH. If TSH suppressed, evaluate for autonomous nodule.
2. FNA indication based on ultrasound risk pattern and size.
3. Bethesda cytology classification + molecular testing:
   • Bethesda III (AUS/FLUS): consider molecular testing; low-risk molecular result can enter surveillance; high-risk mutation favors diagnostic lobectomy.
   • Bethesda IV (follicular neoplasm / oncocytic neoplasm): active surveillance NOT recommended regardless of size. Options: molecular testing or diagnostic lobectomy. FNA cannot assess vascular/capsular invasion required to distinguish benign adenoma from follicular carcinoma.
   • Bethesda V/VI (suspicious/malignant): surgical planning, pre-op neck US for nodal mapping.

Important footnote: Molecular results must be interpreted together with ultrasound, clinical context, not used in isolation.

2. Differentiated Thyroid Carcinoma (DTC) — Papillary Thyroid Carcinoma (PTC)

Active Surveillance (THYR-D principle)

✅ Eligible: cT1a (≤1 cm), N0, M0, purely intrathyroidal, low-risk ultrasound features, no high-risk histology/molecular markers, patient preference. ❌ Not eligible: >1 cm PTC, extrathyroidal extension, nodal/distant metastasis, high-risk subtypes (tall cell, diffuse sclerosing), follicular/oncocytic neoplasms of any size. Monitoring protocol for AS: Neck US every 6–12 months; surgery triggered by tumor growth (>3 mm), new metastatic lymph node, extrathyroidal invasion, patient anxiety.

Surgical selection

1. Lobectomy: 1–4 cm, intrathyroidal, no nodal metastasis, no prior neck radiation, low-risk molecular profile.
2. Total thyroidectomy: >4 cm, multifocal disease, extrathyroidal extension, nodal/distant metastasis, high-risk histology, BRAF/TERT co-mutation, prior neck irradiation.
3. Prophylactic central compartment neck dissection (CCND): selective use, not routine for cN0 low-risk PTC.

Post-op risk stratification, RAI ablation & TSH suppression

1. Low-risk: RAI ablation generally not recommended; TSH target 0.5–2 mIU/L.
2. Intermediate-risk: individualized adjuvant RAI decision; TSH 0.1–0.5 mIU/L.
3. High-risk: adjuvant RAI; TSH <0.1 mIU/L.

RAI remnant ablation can use rhTSH stimulation or LT4 withdrawal.

RAI-refractory progressive DTC systemic therapy

1. Detectable actionable fusion first: NTRK fusion → larotrectinib/entrectinib; RET fusion → selpercatinib.
2. No actionable fusion: lenvatinib preferred first-line (SELECT trial); upon progression, cabozantinib second-line.
3. BRAF V600E mutant: dabrafenib ± trametinib after prior MKI failure.
4. Clinical trials strongly encouraged for all progressive RAI-refractory DTC.

3. Follicular / Oncocytic (Hürthle cell) Neoplasms

Major 2026 change: no active surveillance pathway for follicular or oncocytic neoplasms of any size. FNA cannot evaluate capsular/vascular invasion, the key criteria separating carcinoma from adenoma.

• Diagnostic lobectomy is standard option; total thyroidectomy if carcinoma with extensive vascular invasion or high-risk features.
• Oncocytic carcinoma: generally RAI refractory; advanced disease managed as progressive RAI-refractory DTC.

4. Medullary Thyroid Carcinoma (MTC) — V2.2026 Update on RET Risk Stratification

1. Germline RET testing mandatory for all MTC patients; genetic counseling and cascade family screening.
2. RET variant risk tiering (V2.2026 revision):
   • Highest-risk: M918T
   • High-risk: codon 634, A883F
   • High-intermediate: other pathogenic RET variants
   • Moderate-low risk: V804M
3. Surgery: total thyroidectomy + central neck dissection; lateral neck dissection if lateral nodal disease confirmed.
4. Biochemical surveillance: serum calcitonin + CEA.
5. Advanced/progressive MTC: RET-selective inhibitor selpercatinib/pralsetinib for RET-mutant disease; cabozantinib, vandetanib as multikinase options.

5. Anaplastic Thyroid Carcinoma (ATC)

1. MDT mandatory: airway protection, surgical, radiation, medical oncology, palliative care.
2. Staging: all ATC considered stage IV.
3. Molecular testing for BRAF, NTRK, RET, etc.
   • BRAF V600E: dabrafenib + trametinib ± pembrolizumab.
   • NTRK fusion: larotrectinib/entrectinib.
4. No actionable target: lenvatinib ± pembrolizumab; clinical trial preferred.
5. Palliative radiotherapy for local disease control; palliative care integrated early.

6. Post-treatment Surveillance Framework

DTC

• Low-risk after lobectomy: TSH + neck US annually; Tg not reliable after lobectomy.
• Total thyroidectomy patients: TSH, Tg, anti-TgAb; neck US. Interval tailored by risk.
• Rising Tg / new US lesion: evaluate for recurrence; FNA ± Tg washout of suspicious lymph nodes.

MTC

• Calcitonin, CEA, neck US; chest/abdominal imaging for elevated markers.

7. Cross-reference to prior guideline series

1. NCCN Thyroid 2026 V2: full thyroid carcinoma triage, surgery, RAI, systemic therapy; strict AS only for low-risk PTC microcarcinoma.
2. NASIT 2026: ablation as alternative to surgery/AS in carefully selected low-risk PTC; NCCN remains surgery/AS centered, thermal ablation not primary NCCN recommendation.
3. SIAMS 2026 gynecomastia guideline: monitoring for anti-cancer drug-related endocrine adverse effects.
4. OMA 2026 obesity & CVD: comorbidity management for patients with thyroid cancer and metabolic disease.

Disclaimer: This summary is for academic review only. NCCN guidelines are decision support for multidisciplinary oncology teams; treatment must be individualized after MDT discussion, patient shared decision-making, and local regulatory considerations.