Nasopharyngeal Carcinoma - Staging, Investigations, Treatment

🎗️ Nasopharyngeal Carcinoma - Staging, Investigations & Management

🔍 Investigations of Nasopharyngeal Carcinoma

Primary goals:

• Visualize and localize the lesion (endoscopy ± biopsy)

• Stage extent of local, nodal and distant disease (imaging)

• Baseline assessments for treatment planning and toxicity monitoring

🧭 1- Endoscopic evaluation & biopsy

• Nasal endoscopy / posterior rhinoscopy - inspect nasopharynx, note site (fossa of Rosenmüller common), growth type and lateral/parapharyngeal extension.

Describe the endoscopic appearance of mass in Nasopharyngeal Carcinoma.

• Biopsy = Gold standard for diagnosis.

Where should the biopsy be taken from in case of occult neck metastasis?

🔊 2- Baseline Audiogram

• Detect serous otitis media / conductive loss at presentation.

• Essential before chemoradiation to monitor for ototoxicity and radiation-related SNHL.

🖥️ 3- Imaging

• Contrast-enhanced CT (CECT) neck & nasopharynx

  • Good for initial mapping: primary, parapharyngeal extension, skull-base bone involvement, nodal disease.

  • Useful for surgical/neck planning.

• MRI (preferred for local staging & planning)

  • Best for soft-tissue delineation (parapharyngeal space, perineural spread, marrow infiltration).

  • Superior for assessing skull base, cavernous sinus, optic apparatus and for post-treatment surveillance.

• Ultrasound (neck)

  • Evaluate cervical nodes.

  • USG guided FNAC increases cytology accuracy. Operator-dependent; not fused with cross-sectional imaging.

• 18-FDG PET/CT

  • Useful to detect distant metastasis, assess metabolic extent of loco-regional disease and detect residual / recurrent disease.

  • Consider PET when staging advanced disease or investigating suspected recurrence.

• Bone scan / CT chest / CT abdomen or CT thorax + liver imaging

  • For suspected bony, pulmonary or hepatic metastases.

🧪 4-Lab & molecular markers

• FNAC of nodes — cytologic confirmation of metastatic disease.

• EBV-related tests:

  • Serology: IgA to Viral Capsid Antigen (VCA) - sensitive (screening) and IgA to Early Antigen - more specific.

  • Plasma EBV DNA (quantitative) - highly useful: diagnostic adjunct, prognostic marker, and dynamic marker for treatment response / surveillance.

    • High pre-treatment EBV DNA → correlates with greater tumor burden/advanced stage.

    • Rapid fall to undetectable post-treatment → good response. Persistent or rising levels → persistent disease / recurrence.

  • Nasopharyngeal brushing for EBV DNA — high sensitivity/specificity; can outperform plasma in some settings.

🧾 Staging (AJCC) of Nasopharyngeal Carcinoma

• T (tumor):

  • T1: Tumour confined to nasopharynx, or extends to oropharynx and/or nasal cavity without parapharyngeal involvement

  • T2: Tumour with extension to parapharyngeal space and/or infiltration of the medial pterygoid, lateral pterygoid and/or prevertebral muscles.

  • T3: Tumour invades bony structures of skull base cervical vertebra, pterygoid structures and/or paranasal sinuses

  • T4: Tumour with intracranial extension and/or involvement of cranial nerves, hypopharynx, orbit, parotid gland and/or infiltration beyond the lateral surface of the lateral pterygoid muscle

• N (nodes):

  • Nx: Regional lymph nodes cannot be assessed

  • N0: No regional lymph node metastasis

  • N1: Unilateral metastasis, in cervical lymph node(s), and/or unilateral or bilateral metastasis in retropharyngeal lymph nodes, 6 cm or less in greatest dimension, above the caudal border of cricoid cartilage

  • N2: Bilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the caudal border of cricoid cartilage

  • N3: Metastasis in cervical lymph node(s) greater than 6 cm in dimension and/or extension below the caudal border of cricoid cartilage

• M (metastasis):

  • M0: no distant mets

  • M1: distant metastasis.

🧩 Differential diagnosis of Nasopharyngeal Carcinoma

• Inflammatory: chronic rhinosinusitis, nasal polyposis.

• Infective: nasopharyngeal TB, fungal.

• Other neoplasms: NK/T-cell lymphoma, mucosal melanoma, sinonasal undifferentiated carcinoma, olfactory neuroblastoma, other rare sarcomas.

🎯 Treatment of Nasopharyngeal Carcinoma

• Nasopharyngeal Carcinoma is highly radiosensitive (especially non-keratinizing/undifferentiated types). Radiotherapy is the cornerstone for most stages (I–IVA/B).

• Surgery is NOT first line for primary Nasopharyngeal Carcinoma (anatomic inaccessibility and excellent radiocurability).

PLAN:

• Stage I (and selected low-risk stage II): radical radiotherapy alone.

• Stage II (high tumor load), Stage III–IVA/B: concurrent chemoradiotherapy (CCRT) ± adjuvant chemotherapy.

• Stage IVC (M1): systemic therapy ± local ablative options for oligometastasis.

🧮 Radiotherapy details

• Technique: Intensity-modulated radiotherapy (IMRT) is standard — spares normal structures and improves local control & toxicity profile.

• Dose examples: GTV → ~70 Gy; CTV2 → ~60 Gy (institutional protocols vary).

What is Gross Target volume?

What is Clinical Target volume?

What is Planning Target volume?

💊 Chemotherapy

• Concurrent cisplatin (weekly 30–40 mg/m² or 3-weekly 100 mg/m²) during RT is common for locally advanced disease.

• Adjuvant cisplatin + 5-FU (historically used) or other regimens may follow in high-risk patients.

• Metastatic / recurrent disease: platinum-based doublets (cisplatin + 5-FU). Newer agents (gemcitabine, taxanes, capecitabine, immune therapies) used in selected settings/trials.

• Total cumulative cisplatin dose of ≥200 mg/m² often targeted to confer survival benefit.

🔁 Salvage treatment (persistent / recurrent disease)

1- Local (nasopharyngeal) failure

• Re-irradiation options: stereotactic RT, IMRT re-irradiation, or brachytherapy for small lesions (Ir-192, Au-198) — suitable for lesions ≤2 cm.

• Surgical salvage (nasopharyngectomy): reserved for selected resectable recurrences and where re-irradiation contraindicated. Multiple approaches exist; surgery is technically demanding and morbid:

  • Transpalatal approach

  • Trans-cervico-mandibulo-palatal approach

  • Midfacial degloving approach

  • Maxillary swing approach

  • Facial translocation / lateral skull base approaches

  • Endoscopic / transnasal / transoral and robotic approaches

2- Nodal failure

• Persistent large nodes at 3 months post RT → consider salvage therapy.

• Options: surgical neck dissection ± brachytherapy / re-irradiation.

• Surgery often required: radical neck dissection (high extracapsular spread rates in NPC).

• If vital structures invaded (carotid, brachial plexus): often palliative approach; avoid radical resection of vital structures.

🌍 Treatment of Metastatic disease

• Oligometastatic disease (single/limited mets): consider surgical resection, radiofrequency ablation, or stereotactic radiotherapy (ablative local therapy).

• Systemic therapy for metastatic / disseminated disease - cisplatin + 5-FU first-line; gemcitabine, taxanes, capecitabine as second line.

🔁 Post-treatment surveillance & follow-up of Nasopharyngeal Carcinoma

• Clinical surveillance: frequent early review:

  • Years 0–2: every 2–3 months.
  • Years 3–5: every 3–4 months (or 3–4×/year).
  • After 5 years: 6-monthly to yearly reviews.

• Endoscopic evaluation at follow-ups; biopsy only ≥10–12 weeks post-RT if residual suspicious tissue.

• Imaging (MRI / PET) as indicated for suspected residual / recurrent disease.

• Serial plasma EBV DNA useful for earlier detection of recurrence (rising levels prompt targeted evaluation).

• Audiometry and other organ-specific monitoring for late toxicities.

📈 Prognosis of Nasopharyngeal Carcinoma

• Overall good for early-stage disease with modern IMRT ± chemo.

• 5-year disease-specific survival (illustrative):

  • Stage I: ~100%
  • Stage II: ~90%
  • Stage III / IVA: ~67%
  • Stage IVB: ~68% (depends on nodal/extensive local disease)
  • Stage IVC (distant mets): ~18%

• Best outcomes seen in non-keratinizing / undifferentiated (lymphoepithelioma) — strongly EBV-associated and highly radiosensitive.

• IMRT + concurrent chemo has markedly improved loco-regional control and survival.

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