What is the role of adjuvant maintenance therapy in patients with resected head and neck cancer after postoperative chemoradiotherapy (chemotherapy + radiation therapy)?

From the Guidelines

Adjuvant maintenance therapy is not routinely recommended for patients with resected head and neck cancer who have already completed postoperative chemoradiotherapy. The standard of care for high-risk resected head and neck cancer typically involves postoperative concurrent chemoradiotherapy (usually cisplatin 100 mg/m² every 3 weeks during radiation) followed by observation rather than additional maintenance therapy. This approach is supported by studies such as the US Intergroup trial (RTOG 9501) and the European trial (EORTC 22931), which demonstrated the benefit of concurrent chemoradiotherapy in improving locoregional control and disease-free survival, but not necessarily overall survival 1.

Key Considerations

• The role of chemotherapy/RT in the postoperative management of patients with high-risk cancers of the oral cavity, oropharynx, larynx, or hypopharynx has been clarified by these multicenter randomized trials.
• A combined analysis of data from the two trials showed that patients with extracapsular nodal spread of tumor and/or positive resection margins benefited from the addition of cisplatin to postoperative RT 1.
• The presence of other adverse risk factors—multiple positive nodes (without extracapsular nodal spread), vascular/perineural invasion, and pT4 primary—are established indications for postoperative RT.
• Unlike some other cancer types where maintenance approaches have shown benefit, there is insufficient evidence supporting the use of continued systemic therapy after completing the standard postoperative chemoradiation in head and neck cancer.

Recent Guidelines and Studies

• A recent guideline from 2025 discusses the role of transoral robotic surgery in the multidisciplinary care of patients with oropharyngeal squamous cell carcinoma, highlighting the importance of concurrent cisplatin-based chemotherapy and adjuvant radiation for patients with positive margins after surgery 1.
• However, this guideline does not provide evidence to support the routine use of adjuvant maintenance therapy after postoperative chemoradiotherapy.

Clinical Implications

• The lack of proven survival benefit from adjuvant maintenance therapy, combined with the potential for cumulative toxicities, suggests that observation rather than additional maintenance therapy is the preferred approach.
• Patients should undergo regular surveillance with physical examinations and imaging studies as appropriate to monitor for recurrence.
• Ongoing clinical trials investigating immunotherapy agents in the adjuvant setting may provide future insights into the potential role of maintenance therapy in head and neck cancer.

From the Research

Role of Adjuvant Maintenance Therapy

The role of adjuvant maintenance therapy in patients with resected head and neck cancer after postoperative chemoradiotherapy is a topic of ongoing research.

• Adjuvant radiotherapy is considered a standard approach for patients with locally advanced radically resected head and neck cancer, while postoperative chemotherapy alone is not recommended outside of clinical trials 2.
• Chemoradiotherapy is widely considered superior to radiotherapy in patients at high risk of relapse and may be considered the standard treatment in this population 2.
• The integration of new prognostic and predictive factors, including biomolecular aspects, human papillomavirus infection, and lifestyle, deserves dedicated clinical studies 2.

Clinical Trials and Studies

Several clinical trials and studies have investigated the role of adjuvant maintenance therapy in patients with resected head and neck cancer.

• A phase II trial (RTOG 0024) demonstrated that early postoperative paclitaxel followed by concurrent paclitaxel and cisplatin with radiation therapy is feasible and safe for patients with high-risk head and neck squamous cell carcinoma 3.
• Another study found that postoperative radiotherapy with concurrent cisplatin plus panitumumab is tolerable and demonstrates improved clinical outcome for high-risk, resected, HPV-negative head and neck cancer patients 4.
• A study published in 2025 found that radiotherapy plus cetuximab significantly improved disease-free survival, but not overall survival, with no increase in long-term toxicity, compared with radiotherapy alone for resected, intermediate-risk squamous cell carcinoma of the head and neck 5.
• Postoperative concurrent chemoradiotherapy may benefit older patients with head and neck cancer with positive margins or extranodal extension, particularly those with higher nodal burden 6.

Key Findings

Key findings from these studies include:

• Adjuvant maintenance therapy can improve local control and survival in patients with resected head and neck cancer 2, 3, 5, 6, 4.
• Chemoradiotherapy is a viable option for patients with high-risk head and neck cancer 2, 3, 4.
• The addition of targeted therapies, such as panitumumab or cetuximab, to chemoradiotherapy may improve clinical outcomes in certain patient populations 5, 4.