What is the staging and treatment approach for Carcinoma (Ca) of the oral cavity?

Staging and Treatment Approach for Oral Cavity Carcinoma

Contrast-enhanced CT of the neck with IV contrast is the primary imaging modality for staging oral cavity carcinoma, complemented by FDG-PET/CT for advanced disease (stage III-IV) to assess for distant metastases and guide treatment planning. 1

TNM Staging System (AJCC 8th Edition)

T Staging (Primary Tumor)

• T1: Tumor ≤2 cm with depth of invasion (DOI) ≤5 mm
• T2: Tumor ≤2 cm with DOI >5 mm or tumor >2 cm but ≤4 cm with DOI ≤10 mm
• T3: Tumor >4 cm or any tumor with DOI >10 mm
• T4a: Tumor invades adjacent structures (cortical bone, maxillary sinus, skin of face)
• T4b: Tumor invades masticator space, pterygoid plates, skull base, or encases carotid artery

N Staging (Regional Lymph Nodes)

• N0: No regional lymph node metastasis
• N1: Metastasis in a single ipsilateral lymph node, ≤3 cm without ENE
• N2a: Metastasis in a single ipsilateral node >3 cm but ≤6 cm without ENE
• N2b: Metastasis in multiple ipsilateral nodes, none >6 cm without ENE
• N2c: Metastasis in bilateral or contralateral lymph nodes without ENE
• N3a: Metastasis in a lymph node >6 cm without ENE
• N3b: Metastasis in any node(s) with clinically overt ENE

M Staging (Distant Metastasis)

• M0: No distant metastasis
• M1: Distant metastasis present

Diagnostic Workup

1. Imaging for primary staging:

   • Contrast-enhanced CT of the neck (primary recommendation) 1
   • MRI for better soft tissue delineation when needed
   • FDG-PET/CT for stage III-IV disease 1
   • Dental evaluation including Panorex 2

2. Special techniques:

   • Puffed-cheek technique during CT to better delineate oral cavity tumors, particularly those along gingiva and buccal mucosa 1

3. Pathological assessment:

   • Depth of invasion (DOI) measurement is critical for T staging 3
   • Assessment of number of invaded lymph nodes 4
   • Evaluation of extranodal extension (ENE) 5
   • Perineural and lymphovascular infiltration 1
   • Surgical margins (positive margin defined as tumor ≤1 mm from margin) 1

Treatment Approach Based on Stage

Early Stage Disease (T1-2, N0)

1. Primary treatment options:

   • Surgery is preferred (conservative approaches including transoral techniques) 1, 2
   • For DOI <5 mm and cT1N0, active surveillance of the neck is valid 1
   • For DOI <10 mm, sentinel lymph node biopsy is an option 1
   • Radiotherapy is an alternative when surgery would result in poor functional outcomes 1, 2

2. Surgical approach:

   • Selective neck dissection or sentinel node biopsy for all cT1-2 tumors except T1-2 glottic cancer 1
   • Aim to examine at least 15 lymph nodes for accurate staging 1
   • Minimally invasive approaches (TLM, TORS) when appropriate 1

Advanced Stage Disease (T3-4, N0-3)

1. Resectable disease (T3-4a, N0-3):

   • Surgery followed by risk-adapted adjuvant therapy 1, 2
   • Postoperative RT (58-63 Gy) for high-risk features 1
   • Postoperative chemoradiotherapy (66 Gy with cisplatin) for positive margins and ENE 1

2. Unresectable disease (T4b and/or unresectable nodes):

   • Concomitant chemoradiotherapy 1
   • Induction chemotherapy followed by RT or chemoradiotherapy for responders 1
   • Palliative treatment for non-responders 1

Risk Factors for Recurrence and Adjuvant Therapy

High-risk features requiring adjuvant therapy:

• pT3-4 tumors
• Positive margin (tumor ≤1 mm from margin)
• Close resection margin (1-5 mm)
• Perineural infiltration
• Lymphovascular spread
• Multiple positive lymph nodes (>1)
• Extracapsular nodal infiltration (ENE)
• Poor differentiation (grade 3) 6

Adjuvant therapy recommendations:

• One risk factor: Postoperative RT up to 58 Gy 1
• Multiple risk factors: Postoperative RT up to 63-64 Gy 1
• R1 resection and ENE: Concomitant chemoradiotherapy (66 Gy) with cisplatin 1
• Timing: Postoperative RT should start within 6-7 weeks after surgery 1

Recurrent/Metastatic Disease Management

Treatment based on PD-L1 status and prior treatment:

1. PD-L1 positive, no prior platinum therapy:

   • Pembrolizumab monotherapy 1

2. PD-L1 negative, no prior platinum therapy:

   • Pembrolizumab plus platinum/5-FU 1

3. Prior platinum therapy within last 6 months, immunotherapy-naïve:

   • Nivolumab or pembrolizumab 1

Important Clinical Considerations

• The number of metastatic lymph nodes is a critical predictor of mortality, potentially more important than lymph node size and contralaterality 4
• Examining at least 35 lymph nodes is associated with improved survival 4
• Poorly differentiated tumors (grade 3) have worse prognosis and are more aggressive than grades 1 and 2 6
• Combination of surgery and radiation therapy provides better 5-year survival (52%) for high-grade carcinoma compared to either modality alone 7
• The integration of extranodal extension (ENE) into N staging significantly impacts prognosis and should guide adjuvant therapy decisions 5