Spino-RT: A multicenter, randomized controlled phase III study of adjuvant radiotherapy versus surveillance in patients with cutaneous squamous cell carcinoma (cSCC) at high risk of recurrence.

TPS9614 Background: cSCC is the second most common skin cancer, predominantly affecting elderly individuals. Most cSCCs are diagnosed at an early stage and cured with surgery. Recurrences are usually detected during routine clinical examinations or imaging (lymph-node ultrasound, cervicothoracic CT scan). In patients considered at high-risk, local recurrence rates may reach up to 30%. To date, no randomized trial has established the optimal management of cSCCs at high risk of recurrence after complete resection, and indications for adjuvant radiotherapy are only based on local practices or retrospective studies showing variable and contradictory results. Methods: This ongoing randomized phase III trial (NCT06692556) compares the efficacy and safety of two commonly used strategies (adjuvant radiotherapy versus surveillance) in patients with cSCC at high risk of recurrence. Key eligibility criteria include age ≥ 18 years, histologically confirmed localized cSCC, complete surgical resection and high-risk of recurrence, defined as: 1) microscopic peri nerval involvement (PNI) with or without one additional risk factor, or 2) the presence of two or three risk factors (excluding microscopic PNI): immunosuppression, tumor diameter > 20 mm, specific location (lip/ear/temple), deep invasion (thickness > 6 mm or invasion beyond the subcutaneous fat), poor differentiation or desmoplasia. The primary endpoint is recurrence free-survival, defined as the time from the date of randomization to the date of first documented relapse (local, regional or metastatic) or the date of death. Secondary endpoints include local and metastatic recurrence-free survival, overall survival, safety and quality of life (EORTC QLQ-C30 and QLQ-ELD14). Exploratory objectives include progression-free survival after treatment for local recurrence in the surveillance arm. A total of 120 events will provide 80% power to detect a significant improvement of the recurrence-free survival in favor of the radiotherapy arm (HR=0.6) at a 2-sided alpha risk of 5%. Considering a two-years recurrence-free survival rate of 60% in the control arm, an accrual period of 18 months, 36 months follow-up for the last patient, and 10% of non-evaluable patients, a total of 266 patients is required (133 par arm). Since the start of recruitment (February 2025), 38 patients have been randomized. 35 French health institutions will contribute to recruitment. Clinical trial information: NCT06692556 .