# Locoregionally advanced nasopharyngeal carcinoma (stage III to IVA)

Source: https://onco.cc/cancers/locoregionally-advanced-nasopharyngeal-carcinoma/  
OnCo record `locoregionally-advanced-nasopharyngeal-carcinoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Locoregionally advanced nasopharyngeal carcinoma is nasopharyngeal cancer, the Epstein-Barr-virus-driven cancer behind the nose, that has grown into nearby structures or neck lymph nodes but not further. It is treated without surgery, by precise radiotherapy with cisplatin, usually after gemcitabine and cisplatin chemotherapy and in recent trials with PD-1 immunotherapy; most patients are cured.

## Summary

Nasopharyngeal carcinoma in its endemic form is a non-keratinising carcinoma driven by Epstein-Barr virus, concentrated in southern China, South East Asia, North Africa and the Arctic, and it presents late because the nasopharynx is silent: a neck mass, unilateral hearing loss or blood-stained nasal discharge are the usual first signs, and by then most tumours have reached the skull base or the neck nodes. Plasma EBV DNA is a tumour marker that screens populations (a Hong Kong trial detected early tumours in asymptomatic men), stages the disease and, when still detectable after radiotherapy, identifies patients at high risk of relapse. The tumour is exquisitely sensitive to radiotherapy and chemotherapy, so surgery has no role in primary treatment.

The Intergroup 0099 trial (1998) established concurrent cisplatin chemoradiotherapy over radiotherapy alone, and intensity-modulated radiotherapy, which spares the parotids, brainstem and optic pathways around this awkward target, became standard in the 2000s. Induction chemotherapy was then shown to add benefit: the Sun Yat-sen phase 3 trial of gemcitabine and cisplatin before chemoradiotherapy (New England Journal of Medicine 2019) improved three-year recurrence-free survival from 76.5 to 85.3 percent and overall survival, and docetaxel-cisplatin-fluorouracil (TPF) induction had shown a similar effect, so induction gemcitabine-cisplatin followed by cisplatin chemoradiotherapy is the CSCO-ASCO and NCCN standard for stage III to IVA disease. Metronomic capecitabine for a year after chemoradiotherapy improved failure-free survival in a further Chinese phase 3 (Lancet 2021), and adjuvant therapy directed by post-treatment plasma EBV DNA is being tested in NRG-HN001. PD-1 antibodies have entered the curative setting: the CONTINUUM trial (Lancet 2024) added sintilimab to induction chemotherapy and chemoradiotherapy and improved three-year event-free survival from 76 to 86 percent, and trials of toripalimab and camrelizumab in the same setting are reporting. De-escalation is the other direction: trials omit concurrent cisplatin in low-risk stage II to III patients after induction, reduce radiotherapy dose in good responders and use proton therapy to cut late toxicity, because survivors live for decades with xerostomia, hearing loss, cranial neuropathy and the risk of carotid disease.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Locally advanced NPC; Stage III to IVA nasopharyngeal carcinoma; Non-metastatic advanced nasopharyngeal carcinoma; Endemic EBV-associated nasopharyngeal carcinoma, locoregionally advanced
- Tags: subtype-page; head-and-neck
- Group: head and neck
- Burden: About two thirds of nasopharyngeal carcinoma in endemic southern China and South East Asia presents at stage III or IVA because the tumour site is hidden; it is curable in most patients with chemoradiotherapy.
- Subtypes: Stage III nasopharyngeal carcinoma (T3 or N2); Stage IVA nasopharyngeal carcinoma (T4 or N3); Non-keratinising undifferentiated EBV-associated nasopharyngeal carcinoma (endemic; most cases); Keratinising squamous nasopharyngeal carcinoma (non-endemic, smoking-related, less radiosensitive); Nasopharyngeal carcinoma with detectable plasma EBV DNA after chemoradiotherapy (high relapse risk); Low-risk locoregionally advanced nasopharyngeal carcinoma (de-escalation trials)
- Biomarkers: Plasma EBV DNA (baseline load and post-treatment clearance); EBER in situ hybridisation on biopsy; TNM stage on MRI of the nasopharynx and neck and PET-CT; Response to induction chemotherapy on MRI (adaptive treatment); PD-L1 (not required for PD-1 therapy); Hearing, thyroid and pituitary baselines for late toxicity

## Standard of care

- Staging: MRI of the nasopharynx and neck, PET-CT or CT of chest and abdomen with bone scan, plasma EBV DNA, dental and audiological assessment. ([MRI](https://onco.cc/technologies/mri/), [PET/CT](https://onco.cc/technologies/pet-ct/), [Plasma EBV DNA](https://onco.cc/terms/plasma-ebv-dna/), [Epstein-Barr virus (EBV) in cancer](https://onco.cc/terms/ebv-term/))
- Stage III to IVA, standard: Induction gemcitabine and cisplatin for three cycles followed by intensity-modulated radiotherapy (70 Gy) with concurrent cisplatin; TPF induction as an alternative. ([Gemcitabine + cisplatin](https://onco.cc/drugs/gemcitabine-cisplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/))
- After chemoradiotherapy: Metronomic capecitabine for one year in high-risk patients; EBV DNA-directed adjuvant therapy in trials (NRG-HN001). ([Capecitabine](https://onco.cc/drugs/capecitabine/), [Plasma EBV DNA](https://onco.cc/terms/plasma-ebv-dna/))
- Immunotherapy in the curative setting: PD-1 antibody (sintilimab in CONTINUUM; toripalimab and camrelizumab in trials) added to induction and chemoradiotherapy in high-risk disease, adopted in China. ([Camrelizumab](https://onco.cc/drugs/camrelizumab/), [Toripalimab](https://onco.cc/drugs/toripalimab/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [A Study of YL201 in Combination With Toripalimab and With or Without Cisplatin in Nasopharyngeal Carcinoma.](https://onco.cc/trials/nct07258979/))
- Follow-up: Plasma EBV DNA, MRI and nasopharyngoscopy; management of xerostomia, hearing loss, hypothyroidism and hypopituitarism. ([Plasma EBV DNA](https://onco.cc/terms/plasma-ebv-dna/), [MRI](https://onco.cc/technologies/mri/), [Acupuncture for dry mouth after head and neck radiotherapy](https://onco.cc/technologies/acupuncture-xerostomia/))

## State of the art

- Induction gemcitabine-cisplatin plus cisplatin chemoradiotherapy cures most patients.
- Plasma EBV DNA stages, monitors and now directs adjuvant therapy.
- PD-1 antibodies have improved event-free survival when added to curative treatment in China.

## Open problems

- Which patients can safely have less chemotherapy or radiotherapy is being defined trial by trial.
- Late toxicities of skull-base radiotherapy last for life.
- Non-endemic keratinising disease responds less well and is under-studied.
- PD-1 antibodies in the curative setting are approved and affordable mainly in China.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Nasopharyngeal_carcinoma
- Induction gemcitabine-cisplatin (NEJM 2019): https://doi.org/10.1056/NEJMoa1905287
- CSCO-ASCO NPC guideline 2021: https://doi.org/10.1200/JCO.20.03237
- Wikipedia: https://en.wikipedia.org/wiki/Nasopharyngeal_carcinoma

## Connected records

- cancers: [HPV-positive oropharyngeal cancer](https://onco.cc/cancers/hpv-positive-oropharyngeal-cancer/), [Nasopharyngeal carcinoma](https://onco.cc/cancers/nasopharyngeal/), [Recurrent and metastatic nasopharyngeal carcinoma](https://onco.cc/cancers/recurrent-metastatic-nasopharyngeal-carcinoma/)
- technologies: [Acupuncture for dry mouth after head and neck radiotherapy](https://onco.cc/technologies/acupuncture-xerostomia/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRI](https://onco.cc/technologies/mri/), [PET/CT](https://onco.cc/technologies/pet-ct/), [Platinum agents](https://onco.cc/technologies/platinum/), [Proton therapy](https://onco.cc/technologies/proton-therapy/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Camrelizumab](https://onco.cc/drugs/camrelizumab/), [Capecitabine](https://onco.cc/drugs/capecitabine/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Gemcitabine + cisplatin](https://onco.cc/drugs/gemcitabine-cisplatin/), [Toripalimab](https://onco.cc/drugs/toripalimab/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Epstein-Barr virus (EBV) in cancer](https://onco.cc/terms/ebv-term/), [Head and neck subsites (oral cavity, oropharynx, larynx)](https://onco.cc/terms/head-neck-subsites/), [Plasma EBV DNA](https://onco.cc/terms/plasma-ebv-dna/)
- trials: [A Study of YL201 in Combination With Toripalimab and With or Without Cisplatin in Nasopharyngeal Carcinoma.](https://onco.cc/trials/nct07258979/)
- key papers: [CSCO and ASCO guideline: chemotherapy in combination with radiotherapy for definitive-intent treatment of stage II to IVA nasopharyngeal carcinoma](https://onco.cc/key-papers/paper-csco-asco-nasopharyngeal-carcinoma-guideline-jco-2021/), [Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma](https://onco.cc/key-papers/paper-zhang-gemcitabine-cisplatin-induction-nasopharyngeal-nejm-2019/), [Intergroup 0099: chemoradiotherapy versus radiotherapy in advanced nasopharyngeal cancer](https://onco.cc/key-papers/paper-intergroup-0099-chemoradiotherapy-nasopharyngeal-jco-1998/)

---
JSON: https://onco.cc/api/v1/entities/locoregionally-advanced-nasopharyngeal-carcinoma.json