📜 The Literature

Was the trial question clear, and was the method appropriate to answer it?

The trial addressed a clear and relevant clinical question: Is radiotherapy (RT) superior or comparable to transoral robotic surgery plus neck dissection (TORS + ND) in managing early-stage oropharyngeal squamous cell carcinoma (OPSCC), particularly in terms of swallowing-related quality of life (QOL)? Given the rising incidence of OPSCC and the lack of long-term comparative data between these treatment modalities, this question is highly pertinent. The use of a randomised controlled trial (RCT) design is the gold standard for comparing treatment interventions, making it an appropriate method for addressing this clinical question.

Was the study population representative of the target population?

The population included patients aged 18 and above with T1-T2, N 0-2 stage OPSCC, mostly HPV-positive, which is representative of the demographic that most frequently presents with OPSCC. The exclusion criteria seem appropriate to ensure the study focused on a homogenous group regarding the cancer stage and general health status. Most patients were men (85%), which reflects the typical gender distribution in OPSCC, although the study could have aimed for a more gender-balanced cohort. Furthermore, it is notable that the trial was conducted across six international centres, enhancing its generalisability.

Was the study design appropriate?

The open-label, parallel-group, phase II randomised controlled trial design was appropriate, given the need for long-term QOL comparison between the two treatment modalities. The study had a primary outcome of swallowing QOL at 1 year, measured by a validated tool (MD Anderson Dysphagia Inventory - MDADI), with secondary outcomes including adverse events, overall survival, and progression-free survival. Randomisation and stratification by HPV status (p16) were well-implemented. However, the open-label design (lack of blinding) could introduce bias in subjective QOL outcomes, as both patients and physicians were aware of the treatment allocations.

Was the data collected and analysed correctly?

The data was collected using validated tools (e.g., MDADI, Common Toxicity Criteria for Adverse Events). The intention-to-treat analysis used is a robust approach, and the statistical methods, including linear mixed-effects models for longitudinal analysis, are appropriate for evaluating changes over time. There were limitations, such as attrition in QOL data over time, which reduces the power for long-term comparisons. Additionally, post-hoc analyses were conducted for subgroup comparisons, which the authors acknowledge are hypothesis-generating rather than definitive due to small sample sizes in some groups.

Were the results interpreted correctly?

The authors correctly concluded that while RT showed a slight advantage in swallowing QOL over TORS + ND, this difference did not meet the threshold for clinical meaningfulness over time. They also highlighted that both treatments had distinct toxicity profiles, with RT causing more ototoxicity and neutropenia, while TORS led to more pain and trismus. Oncologic outcomes (survival and progression-free survival) were comparable between the two groups, further supporting the authors' emphasis on shared decision-making between patients and clinicians based on individual risk preferences. The authors acknowledged limitations, such as modest sample size and evolving treatment standards, and their conclusions are cautious and well-supported by the data.

Summary

In summary, the study was well-conducted and provided valuable insights into the long-term comparison between RT and TORS in OPSCC, though it was limited by the sample size and open-label design.