BackgroundOver the past decade, therapeutic options in head and neck supraglottic squamous cell carcinoma have constantly evolved. The classical total laryngectomy has been partially replaced by alternative organ- and function-sparing techniques with the same prognosis but less morbidity, such as Radiotherapy, Transoral Laser Microsurgery (TLM) and Trans-Oral Robotic Surgery (TORS). Up to now, a prospective comparison of these innovant techniques has not been conducted.Methods/designWe will conduct an original international multicentric prospective nonrandomized clinical trial to compare the efficacy between these treatments (Arm 1: Radiotherapy ± chemotherapy; Arm 2: TLM and Arm 3: TORS) with 4 classes of outcomes: quality of life (QoL), oncological outcomes, functional outcomes and economic resources. The population will include cT1-T2 /cN0-N1/M0 supraglottic squamous cell carcinoma. The primary outcome is a Clinical Dysphagia QoL evaluation assessed by the MD Anderson Dysphagia questionnaire. Secondary outcomes include others QoL evaluation, oncological and functional measures and cost parameters. The sample size needs to reach 36 patients per arm (total 108).DiscussionIn the current literature, no prospective head-to-head trials are available to compare objectively these different treatments. With the increase of highly efficient treatments and the increase of oncological survival, it is imperative also to develop management strategies that optimize QoL and functional results. We will conduct this innovate prospective trial in order to obtain objective data in these two main issues.Trial registrationNCT05611515 posted on 10/11/2022 (clinicaltrial.fgov).