Caution regarding assessment of toxic effects and survival in treatment de-escalation with radiotherapy vs transoral surgery for human papillomavirus-associated oropharyngeal cancer

The declared aim of the ORATOR2 randomized clinical trial1 recently reported by Palma et al in JAMA Oncology was to compare outcomes in patients with human papillomavirus–associated oropharyngeal cancer treated with primary radiotherapy (RT) vs primary transoral surgical (TOS) approach and to provide a high level of evidence to guide the selection of treatment options for a subsequent phase 3 trial. To have a direct comparison, a trial (eg, EORTC 1420) should aim to compare 2 samples receiving a single-treatment modality with a limited proportion of patients requiring adjuvant treatment for the lymph node status (multiple lymph nodes or greater than 3 cm) and/or adverse features, such as positive margins and extranodal extension discovered on the surgical specimen.