NCCN Guidelines® Insights: Head and Neck Cancers, Version 2.2025

Key guideline recommendations

1. T1N0M0 nasopharyngeal tumours should be treated with definitive radiotherapy alone; radiotherapy alone may also be used for T2N0, but with high-risk features (such as bulky tumour volume or high serum EBV DNA levels) concurrent systemic therapy may be indicated.

   Category 2A (NCCN default)

2. Induction chemotherapy followed by concurrent systemic therapy/radiotherapy is the preferred approach for locoregionally advanced disease (T3N1–N3; T4N0–3; or T0–2N2–3); for patients who have not received induction, adjuvant chemotherapy after chemoradiotherapy is recommended.

   Preferred (category 2A)

3. If induction chemotherapy is used, gemcitabine–cisplatin (GC) and modified TPF are both preferred options for EBV-associated NPC.

   Preferred (category 2A)

4. Cisplatin concurrent with radiotherapy is recommended for all patients without contraindications; substitution of carboplatin or other platinums should be limited to patients unable to receive cisplatin.

   Category 2A (NCCN default)

5. Concurrent chemoradiotherapy alone is recommended for T0–2N1 patients and may be considered in selected lower-risk T3N0 patients.

   Category 2A (NCCN default)

6. If adjuvant chemotherapy is used, the preferred option remains cisplatin–5-FU (PF); metronomic capecitabine is supported by a phase 3 trial as an adjuvant chemotherapy option for stage III–IVa (except T3–4N0 and T3N1).

   Category 2A (NCCN default)

7. IMRT is preferred; a dose of about 70 Gy in standard fractions of about 2 Gy to the primary tumour and involved nodes (one alternative: 2.12 Gy daily in 33 fractions to about 69.7 Gy); low-risk subclinical disease 44 to 50 Gy in 2 Gy fractions (or 54 to 56 Gy in fractions of 1.6 to 1.7 Gy given simultaneously in the same plan).

   Category 2A (NCCN default)

8. No trial has yet shown an overall survival benefit from adding immune checkpoint inhibitors to sequential chemoradiotherapy in locoregionally advanced NPC; adding them at this stage is therefore considered premature.

   Panel statement (no category)

9. Gemcitabine–cisplatin (GC) is recommended for first-line treatment of metastatic NPC based on category 1 evidence (survival superiority over PF).

   Category 1

10. Toripalimab with gemcitabine–cisplatin is a category 1 preferred option for first-line treatment of recurrent or metastatic NPC; single-agent toripalimab is also a preferred option for progression on or after platinum-containing therapy.

    Category 1, preferred (first line)

11. Tislelizumab (with GC in the first line, and in later lines) is a category 2B option and is not FDA-approved for NPC; pembrolizumab for previously treated PD-L1-positive recurrent/metastatic NPC (category 2B) and nivolumab for previously treated non-keratinising recurrent/metastatic NPC (category 2B) are options.

    Category 2B

12. In oligometastatic disease with a complete or near-complete response to systemic therapy, definitive-dose radiotherapy to the primary tumour and involved regional nodes is recommended; maintenance capecitabine (without concurrent radiotherapy) after induction chemotherapy is an option for oligometastatic patients with PS 0 to 1.

    Category 2A (NCCN default)

Study population

Clinical significance and place in guidelines

Limitations