What is the role of neo-adjuvant (new adjunct) treatment in advanced oral cancer?

Role of Neoadjuvant Treatment in Advanced Oral Cancer

Neoadjuvant chemotherapy is highly beneficial in advanced oral cancer, with 3-drug regimens (Docetaxel-Cisplatin-5-FU) showing superior survival outcomes compared to 2-drug regimens in borderline resectable cases. 1

Benefits of Neoadjuvant Therapy in Oral Cancer

• Neoadjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC), particularly in borderline resectable cases 1
• NACT can reduce tumor size in technically unresectable oral cancers, enabling successful surgical resection in approximately 43% of cases, leading to improved overall survival 2
• The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has demonstrated significant improvement in overall survival compared to 2-drug regimens (Docetaxel-Cisplatin) in phase-3 randomized studies 1
• Long-term data shows patients receiving more than 2-drug NACT had 10-year overall survival of 21% versus 5.1% for those receiving 2-drug regimens (p<0.001) 1

Treatment Approach Based on Resectability

For Borderline Resectable Disease:

• Initial treatment with neoadjuvant chemotherapy followed by response assessment 1
• Patients who become resectable after NACT should undergo surgery followed by appropriate adjuvant therapy 1
• Patients who remain unresectable should receive definitive chemoradiation, palliative chemotherapy, radiotherapy, or best supportive care based on general condition 1

For Technically Unresectable Disease:

• NACT with 2 cycles followed by reassessment for potential surgical resection 2
• Patients who undergo successful surgery after NACT show significantly better median overall survival (19.6 months) compared to non-surgical treatment (8.16 months) 2
• Locoregional control rates at 24 months are significantly higher in patients undergoing surgery after NACT (32%) versus non-surgical treatment (15%) 2

Emerging Neoadjuvant Approaches

• Neoadjuvant immunotherapy is showing promise as a new therapeutic approach for advanced oral cancer 3
• Recent trials demonstrate that neoadjuvant PD-1 inhibitor (camrelizumab) combined with TPF chemotherapy achieved major pathological response in 76.4% of patients with resectable locally advanced OSCC 4
• The combination of immunotherapy with chemotherapy in the neoadjuvant setting showed 2-year event-free survival rates of 91.2% compared to 52.9% with immunotherapy alone 4
• Even a single cycle of neoadjuvant immunotherapy (Pembrolizumab) can lead to significant regressive tumor changes with increased immune infiltration and tumor necrosis 3

Practical Considerations

• Response to neoadjuvant therapy should be carefully assessed to determine subsequent treatment approach 1
• Patients who achieve pathological complete response (pCR) after NACT have significantly better 5-year overall survival (45.3%) compared to those who don't (13.3%) 1
• The most common indication for NACT in oral cancers is peritumoral edema extending to the zygoma 1
• Surgical treatment remains the mainstay of therapy for patients with oral cancer, particularly in advanced stages, with NACT serving as an important tool to enable surgery in borderline or unresectable cases 5

Monitoring and Follow-up

• Regular assessment of response after neoadjuvant therapy is essential for treatment planning 1
• For patients receiving neoadjuvant immunotherapy, evaluation of T-cell infiltration and PD-L1 expression before and after treatment can provide valuable information about treatment response 3
• Long-term follow-up is crucial as NACT has demonstrated sustained survival benefits at 10 years in patients with borderline resectable oral cavity cancer 1