Title: “Adjuvant Radiotherapy Versus Observation Following Curative Surgery for Early-Stage Oral Squamous Cell Carcinoma”
Authors: Sudhir Vasudevan Nair, Tejpal Gupta, Swapnil Ulhas Rane, Sadhana Kannan, Sarbani Ghosh-Laskar, Gouri Pantvaidya, Pankaj Chaturvedi, C. S. Pramesh, Asawari Patil, Rajendra Toprani, Kaustubh Patel, Kinjal Jani, Aseem Mishra, Sambit Swarup Nanda, Ashok Kumar Das, Mouchumee Bhattacharyya, Krishnakumar Thankappan, Subramania Iyer Sr., Geetha Muttath, Samarth Kamlesh Chhatbar
The phase III AREST trial evaluated whether adjuvant radiotherapy adds benefit after curative surgery in patients with early-stage, node-negative oral squamous cell carcinoma who had intermediate-risk pathological features.
The study addressed an important clinical question in oral cancer care: whether patients with adequately resected pT1-T2, pN0 oral squamous cell carcinoma need postoperative radiotherapy when they have risk factors such as depth of invasion 5–10 mm, perineural invasion, lymphovascular emboli, or poor differentiation.
Although adjuvant radiotherapy is commonly considered in higher-risk disease, its role in this specific early-stage, node-negative setting has remained uncertain and largely supported by retrospective evidence.
A Trial Focused On Intermediate-Risk Early Oral Cancer
AREST was a multicenter, open-label, phase III randomized controlled trial conducted by the Head and Neck Cooperative Oncology Group across several cancer centers in India.
Patients were eligible if they had undergone adequate curative surgery, defined as clear margins of at least 5 mm and at least an ipsilateral level I–III neck dissection with 16 or more lymph nodes removed. All patients had one or more intermediate-risk factors but no nodal involvement.
After surgery, patients were randomly assigned to either observation or adjuvant radiotherapy. Radiotherapy was delivered as 60 Gy in 30 fractions over 6 weeks to the resected tumor bed and at-risk neck nodal region.
The primary endpoint was loco-regional recurrence-free survival, measured from randomization to the first documented local or regional recurrence.
Key Findings From AREST
A total of 392 patients were randomized after curative surgery, including 191 patients assigned to adjuvant radiotherapy and 201 patients assigned to observation. Baseline characteristics were balanced between the two treatment groups.
At a median follow-up of 47.2 months, adjuvant radiotherapy significantly improved loco-regional recurrence-free survival.
In the intention-to-treat population, the 3-year loco-regional recurrence-free survival was 89.2% with adjuvant radiotherapy compared with 80.9% with observation. This corresponded to a hazard ratio of 0.52 and a statistically significant improvement.
In the per-protocol analysis, the benefit was even more pronounced. The 3-year loco-regional recurrence-free survival was 91.1% with adjuvant radiotherapy versus 80.9% with observation, with a hazard ratio of 0.43.
Adjuvant radiotherapy also reduced the cumulative incidence of loco-regional failure. In the intention-to-treat population, loco-regional failure occurred in 10.6% of patients receiving adjuvant radiotherapy compared with 18.9% of patients under observation. Similar findings were seen in the per-protocol population, with failure rates of 8.7% versus 18.9%, respectively.
Survival Benefit Was Not Demonstrated
Despite the significant improvement in loco-regional control, the trial did not show a significant difference in disease-free survival or overall survival between the two groups.
This distinction is clinically important. AREST supports the use of adjuvant radiotherapy to reduce local and regional recurrence in selected patients, but the reduction in recurrence did not translate into a measurable survival advantage within the reported follow-up period.
Subgroup analysis suggested that patients with oral tongue cancers appeared to derive greater benefit from adjuvant radiotherapy compared with those with buccal mucosa cancers.
Why This Matters
AREST provides prospective randomized evidence in a setting where treatment decisions have often depended on institutional practice, physician judgment, and retrospective data.
For patients with early-stage, node-negative oral squamous cell carcinoma who undergo high-quality surgery but still have intermediate-risk features, adjuvant radiotherapy significantly reduced the risk of loco-regional recurrence. The findings are especially relevant for patients with oral tongue tumors, where the benefit appeared greater.
At the same time, the absence of a significant disease-free or overall survival benefit highlights the need for careful patient selection. The decision to recommend adjuvant radiotherapy must balance the improved loco-regional control against treatment burden, toxicity, and long-term functional effects.
The AREST trial suggests that postoperative radiotherapy can improve disease control after surgery in selected patients with early-stage oral squamous cell carcinoma, while also reinforcing that not every reduction in recurrence automatically leads to improved survival.
Abstract link
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