Oral Cavity SCC: Definitive Treatment

Oral Cavity SCC: Definitive Treatment: overview

This algorithm covers definitive treatment of oral cavity squamous cell carcinoma, including mucosal lip, by stage, with a final step for adjuvant therapy by pathologic risk. Early disease (T1-2 N0) is treated preferentially with resection of the primary, with or without neck dissection or sentinel lymph node biopsy, and definitive radiotherapy is the alternative. For resectable locally advanced disease (T3 N0, T1-3 N1-3, T4a N0-3), surgery with neck dissection is preferred, and a clinical trial is also listed.

For tumors with PD-L1 CPS 1 or higher, excluding N3 disease, the chart adds a perioperative pembrolizumab pathway: neoadjuvant pembrolizumab, surgery, radiotherapy plus pembrolizumab (with cisplatin for extranodal extension or a positive margin), then adjuvant pembrolizumab, supported by KEYNOTE-689, which improved event-free survival in high-risk resected disease. Adjuvant therapy follows pathologic risk: observation without nodal disease or adverse features, consideration of radiotherapy for a single node, and cisplatin chemoradiation for extranodal extension with or without a positive margin, an approach supported by RTOG 9501.

Step by step

• Early disease (T1-2 N0): resection of the primary with or without neck dissection or sentinel node biopsy preferred, or definitive radiotherapy.
• Resectable locally advanced disease (T3 N0, T1-3 N1-3, T4a N0-3): surgery with neck dissection preferred, or a clinical trial.
• Resectable locally advanced disease with PD-L1 CPS 1 or higher, except N3: neoadjuvant pembrolizumab, surgery, radiotherapy plus pembrolizumab (with cisplatin for extranodal extension or positive margin), then adjuvant pembrolizumab (KEYNOTE-689).
• Adjuvant, no positive node and no adverse features: observe.
• Adjuvant, one node (pN1) with no other risk features: consider radiotherapy.
• Adjuvant, extranodal extension with or without positive margin: cisplatin chemoradiation.
• Adjuvant, positive margin: re-resection, or chemoradiation or radiotherapy; other risk features: radiotherapy with or without concurrent chemotherapy.

Trials behind this algorithm

• KEYNOTE-689 Uppaluri R et al, NEJM, 2025; PMID: 40532178
• RTOG 9501 Cooper JS et al, N Engl J Med, 2004; PMID: 15128893