Primary Treatment for Oral Squamous Cell Carcinoma

Treatment Approach Based on Disease Stage

The primary treatment for oral squamous cell carcinoma is surgery followed by adjuvant radiotherapy or chemoradiotherapy in cases with adverse pathological features, with primary surgical treatment being the preferred approach for T3/T4 oral cavity cancers 1, 2
Early disease should be treated with a single-modality approach whenever possible 1, 3
Conservative surgery, including transoral laser microsurgery or transoral robotic surgery, is an option for early stage disease 4
Radiotherapy, including external beam or brachytherapy for selected stage I cases, is also an option for early stage disease 4
The choice between surgery and radiotherapy should be based on expected functional outcomes and treatment-related morbidity 4

Postoperative radiotherapy is recommended for patients with pT3-4 tumors, resection margins with macroscopic or microscopic residual disease, perineural infiltration, lymphatic infiltration, more than one invaded lymph node, and presence of extracapsular infiltration 1, 2
Postoperative chemoradiotherapy is recommended for patients with R1 resection and extracapsular extension 1, 2

All patients should be treated with intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) 3
For concurrent chemoradiotherapy, the standard chemotherapy regimen is cisplatin at 100 mg/m² on days 1, 22, and 43 of radiotherapy (70 Gy) 1, 2
Alternatives to cisplatin include carboplatin combined with 5-FU and cetuximab with radiotherapy 1, 2

For patients with PD-L1 expressing tumors, pembrolizumab in combination with platinum/5-FU or pembrolizumab monotherapy is recommended 1, 5
For patients with non-PD-L1 expressing tumors, platinum/5-FU/cetuximab remains standard therapy 1, 5
For patients who progress within 6 months of platinum therapy, nivolumab or pembrolizumab is recommended 1, 5

Treatment should be discussed in a multidisciplinary team including supportive specialties 1, 6
Patients should be treated at high-volume facilities for better outcomes 1, 6
DPD testing is recommended before initiating 5-FU treatment 1, 6
Neck dissection is not recommended in cases of negative FDG-PET and normal size lymph nodes at 12 weeks post-CRT 1, 2

Close monitoring is essential to detect early locoregional recurrence or new primaries 2
Follow-up should include the entire head and neck multidisciplinary team 2
The risk of disease relapse is 40-60% for locally advanced disease, with most recurrences occurring within the first 2 years 2

IOC therapy is recommended for selected early‑stage (T1‑T2) oral cavity carcinomas when a single‑modality treatment approach is preferred, offering a localized radiation option without the need for surgery. 7

IOC therapy should not be used for advanced (T3‑T4) oral cavity cancers, which require primary surgical resection as the standard of care. 7

Transoral laser microsurgery (TLM) or transoral robotic surgery (TORS) are viable surgical alternatives for early‑stage disease; however, postoperative radiotherapy may be necessary if adverse pathological features are present. 7
Primary surgical resection with adjuvant therapy is the recommended approach for T3‑T4 lesions. 7
External beam radiotherapy (EBRT) alone can be employed as a non‑IOC radiation option for stage I disease. 7
Brachytherapy is an alternative for selected stage I oropharyngeal or oral cavity subsites. 7

The choice between IOC therapy and surgical modalities should be based on expected functional outcomes, treatment‑related morbidity, and institutional expertise, with a preference for single‑modality treatment in early‑stage disease. 7

Using IOC therapy for advanced T3‑T4 disease constitutes inappropriate patient selection, as these cases mandate primary surgical management. 7