Effectiveness of bilateral tongue base mucosectomy by transoral robotic surgery or transoral laser microsurgery in combination with tonsillectomy in identifying head and neck primary cancer of unknown primary: a randomized phase 2 protocol (RoboCUP trial).

Abstract

Background: In cases of prevalent lymphadenopathy in the head and neck cancer region, identifying the primary tumor site allows for more precise radiotherapy targeting. This improves treatment by reducing the volumes of mucosal irradiation and potentially lowering morbidity. An extensive diagnostic workup, including FDG PET-CT imaging and bilateral tonsillectomy, has been shown to identify the primary cancer in 60% of cases. Mucosectomy of the tongue base holds promise for detecting additional primary sites. When performed using minimally invasive endoscopic techniques such as transoral robotic surgery (TORS) or transoral laser microsurgery (TLM), mucosectomy results in minimal morbidity. However, the effectiveness of tongue base mucosectomy in detecting primary tumors has yet to be evaluated in a randomized trial involving patients with lymphadenopathy of unknown primary.

Methods: The RoboCUP trial is a multicentre, open-label, randomized, non-comparative phase 2 trial aiming to evaluate the benefit of bilateral TORS or TLM-assisted tongue base mucosectomy in association to tonsillectomy in the assessment of prevalent cervical lymphadenopathy with a negative exhaustive diagnostic workup. The main endpoint is the proportion of patients with detection of a primary cancer. Surgery will consist in tongue base mucosectomy plus tonsillectomy in the experimental arm, and the standard of care, i.e. tonsillectomy alone in the control arm. Patients will then be treated by intensity modulated radiotherapy, possibly with chemotherapy as radiosensitizer, per current guidelines. Using a single-stage Fleming design, 36 patients will be enrolled in the experimental arm, and 36 patients in the control arm.

Discussion: This trial aims to improve the diagnostic performances, i.e. detection of primary tumor, in patients with head and neck carcinoma of unknown primary. It is expected that the subsequent therapeutic changes could enhance radiotherapy accuracy, and could improve the prognosis, toxicity profiles and quality-of-life of patients.

Trial registration: NCT04767048, registered February, 19, 2021.