What is the overview and recommended management for buccal squamous cell carcinoma?

Buccal Squamous Cell Carcinoma: Overview and Management

Introduction

Buccal squamous cell carcinoma (SCC) is an aggressive malignancy of the oral cavity that presents with visible lesions or sores, often painless in early stages, and carries a high risk of locoregional recurrence (approximately 50%) despite treatment. 1, 2 This tumor represents a significant subset of oral cavity cancers, particularly prevalent in populations with tobacco and betel quid exposure, and demonstrates distinct clinical behavior compared to other oral cavity subsites. 1, 3

Key Clinical Features

• Risk factors include tobacco smoking, smokeless tobacco use, heavy alcohol consumption, and betel quid chewing 1
• Presentation typically involves visible mucosal lesions, ulcerations, or masses on the buccal mucosa, with pain developing in advanced stages 1
• Aggressive behavior characterized by high recurrence rates (50% at median 12 months) and significant cervical metastatic potential (23% present with nodal disease at diagnosis) 4
• T-stage distribution shows buccal SCC presents at higher T stages compared to other oral cavity subsites, with more T2 tumors at presentation 5

Diagnostic Approach

Essential Diagnostic Elements

• Tissue diagnosis via biopsy is mandatory for confirmation 1
• Imaging studies (CT/MRI) for accurate staging and treatment planning 1
• Pathologic assessment must document: tumor grade, depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion (PNI), and margin status 1, 5
• Nodal evaluation is critical as lymph node metastasis occurs in approximately 50% of patients and carries significant prognostic implications 1

Critical Prognostic Factors

Tumor differentiation is the single most significant factor affecting prognosis and survival in buccal SCC. 3 Additional high-risk features include:

• Nodal status and extracapsular extension are the only significant predictors of overall survival 2
• Perineural invasion and positive margins increase odds of recurrence specifically in buccal SCC 5
• Tumor size (T-stage) correlates with cervical metastases (P=0.002) 4
• Age ≥65 years increases all-cause mortality risk in buccal SCC patients 5

Management Algorithm

Early-Stage Disease (T1-T2, N0)

Early-stage buccal SCC should be treated with single-modality surgical resection including elective ipsilateral neck dissection. 6, 3

• Transoral wide excision with adequate margins (aim for ≥5mm) 2
• Elective neck dissection (ND) is recommended even for cN0 disease, as it exerts a positive effect on locoregional control and decreases recurrence risk 3, 7
• Ipsilateral selective neck dissection (levels I-III minimally) should be performed given the 23% occult metastasis rate 4

Postoperative radiation therapy indications (start within 6-7 weeks of surgery): 6

• pT3-T4 tumors
• Positive margins (R1/R2)
• Perineural invasion
• Lymphovascular invasion

• 1 invaded lymph node

• Extracapsular extension

Locally Advanced Disease (T3-T4 or N+)

Primary surgical treatment followed by adjuvant radiotherapy or chemoradiotherapy is the preferred approach for T3/T4 oral cavity cancers. 6

Surgical Management

• Composite resection (including mandible/maxilla if involved) for adequate oncologic clearance 2, 7
• Through-and-through resection including skin if tumor extends to overlying tissues 7
• Comprehensive neck dissection (ipsilateral mandatory; consider bilateral for midline-approaching tumors) 4

Adjuvant Therapy Selection

Postoperative chemoradiotherapy (CRT) is mandatory for: 6

• R1 resection (microscopically positive margins)
• Extracapsular rupture/extension

Postoperative radiotherapy alone for: 6

• pT3-T4 tumors without ECE
• Perineural invasion
• Lymphovascular invasion
• Multiple positive nodes without ECE

Standard chemoradiotherapy regimen: 6

• Cisplatin 100 mg/m² on days 1,22, and 43
• Concurrent with radiotherapy (70 Gy)
• Delivered via IMRT or VMAT techniques

For cisplatin-unfit patients: 6

• Carboplatin + 5-FU concurrent with RT, OR
• Cetuximab concurrent with RT, OR
• Hyperfractionated/accelerated RT without chemotherapy

Recurrent/Metastatic Disease

First-Line Systemic Therapy

For PD-L1 expressing tumors (CPS ≥1): 6

• Pembrolizumab + platinum/5-FU when rapid tumor shrinkage needed
• Pembrolizumab monotherapy as alternative (particularly if PD-L1 TPS ≥50%)

For PD-L1 negative tumors: 6

• Platinum/5-FU/cetuximab (EXTREME regimen) remains standard therapy

Second-Line Therapy (After Platinum Failure)

Nivolumab is the standard second-line option for patients progressing within 6 months of platinum therapy (median OS 7.5 vs 5.1 months with single-agent chemotherapy). 6

Alternative options after platinum failure: 6

• Cetuximab (FDA-approved, median OS 5.2-6.1 months)
• Taxanes ± cetuximab ± methotrexate (no randomized trial support)

Critical Management Principles

Multidisciplinary Team Requirements

All treatment decisions must be discussed in a multidisciplinary tumor board including: 6

• Head and neck surgeons
• Radiation oncologists
• Medical oncologists
• Pathologists
• Radiologists
• Supportive care specialists (speech/swallowing, nutrition, psychology)

Treatment Setting

Patients should be treated at high-volume facilities with expertise in head and neck oncology. 6

Common Pitfalls and Caveats

• Avoid observation of the neck in cN0 buccal SCC: The 23% occult metastasis rate and aggressive behavior mandate elective neck dissection even for early-stage disease 3, 4
• Do not delay adjuvant therapy: Postoperative RT/CRT must start within 6-7 weeks of surgery to optimize outcomes 6
• Poorly differentiated tumors require aggressive systemic therapy: Degree of differentiation is the most significant prognostic factor; consider adjuvant chemotherapy even for early-stage poorly differentiated tumors 3
• Perineural invasion and positive margins are particularly ominous in buccal SCC: These factors specifically increase recurrence risk in buccal tumors more than other oral cavity subsites 5
• Age matters in buccal SCC: Patients ≥65 years have increased mortality risk; consider this in treatment intensity decisions 7, 5

Follow-Up Strategy

Close surveillance is mandatory given the 50% recurrence rate, with most recurrences occurring within the first 2 years. 6 Follow-up should include:

• Head and neck examination with flexible endoscopy
• Multidisciplinary team involvement (physicians, dietician, speech/swallowing specialists)
• Monitoring for second primary tumors (2-4% annual incidence)
• Long-term toxicity assessment