Home › Trials › NCT06692556

Adjuvant radiation versus monitoring after surgery for high-risk cutaneous squamous cell carcinoma

Randomized Comparative Multicenter Phase III Study of a Strategy Integrating Adjuvant Radiation Therapy Versus Strategy Based on Monitoring in the Treatment of Carcinomas Spinocellular With High Risk of Recurrence

Phase 3 Interventional Centre Leon Berard · NCT06692556

This compares adding adjuvant radiation after complete surgery to close monitoring to see if people with high-risk cutaneous squamous cell carcinoma stay free of cancer longer.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment266 (estimated)
Ages18 Years and up
SexAll
SponsorCentre Leon Berard Academic / other
Drugs / interventionsradiation
Locations28 sites (Le Puy-en-Velay, Auvergne-Rhône-Alpes and 27 other locations)
Trial IDNCT06692556 on ClinicalTrials.gov

What this trial studies

This phase 3 randomized study assigns adults with completely excised high-risk cutaneous squamous cell carcinoma to either adjuvant radiotherapy or active surveillance. The primary endpoint is disease-free survival, and participants are followed every 4 months for two years and then every 6 months with clinical exams, imaging, treatment tracking, and quality-of-life questionnaires. Eligible patients have R0 surgical excision and predefined high-risk features such as microscopic perineural invasion, large tumor size, specific high-risk locations (lip/ear/temple), deep invasion, or limited immunosuppression. The protocol is designed as the first prospective comparative evaluation to determine whether routine adjuvant radiotherapy improves outcomes versus observation.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed localized cutaneous squamous cell carcinoma who had complete (R0) surgical excision and meet predefined high-risk criteria such as microscopic perineural invasion, large tumor diameter, specific locations, deep invasion, or limited immunosuppression.

Not a fit: Patients with low-risk CSCC, metastatic disease, incomplete (R1) resections, or those who cannot safely receive radiotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If effective, adjuvant radiotherapy could reduce recurrence and improve disease-free survival for patients with high-risk CSCC.

How similar studies have performed: Retrospective series and clinical experience suggest adjuvant radiotherapy may lower recurrence risk, but prospective randomized evidence is lacking and this is the first planned prospective comparative evaluation.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

I1. Patients aged ≥ 18 years at the time of signing the informed consent form; I2. Patients with histologically confirmed localized cutaneous squamous cell carcinoma;

Note: Patients with carcinoma of the external auditory canal may be included in the study;

I3. Patients treated with complete surgical excision (R0), regardless of the margin (submillimeter or supramillimeter);

I4. Disease with a high risk of recurrence defined by one of the following scenarios:

* presence of microscopic EPN without any other risk factors;
* presence of microscopic EPN with a single other risk factor;
* presence of 2 risk factors other than microscopic EPN;
* presence of 3 risk factors other than microscopic EPN;

Note: The risk factors considered are immunosuppression (limited to untreated hematologic disease), a tumor diameter \>20 mm (longest axis, measured preferably clinically, or, failing that, histologically), a specific location (lip/ear/temple), deep invasion (tumor thickness \>6 mm (Breslow) or invasion beyond the subcutaneous fat), poor differentiation, or desmoplasia;

I5. Patient informed and having signed a consent form to participate in the study; I6. Patient enrolled in a health insurance plan (or beneficiary of such a plan).

Exclusion Criteria:

NI1. Patients with in situ or mixed CEC; NI2. History of CEC with a high risk of recurrence in the same lymphatic drainage area (head and neck, trunk, or limb) within 2 years prior to the randomization date; NI3. History of CEC treated with systemic therapy; NI4. Patients with SCC localized to the endonasal, intraoral, anogenital, or vulvar mucosa;

NI5. Patients with recurrent SCC or SCC at very high risk of recurrence defined by one of the following criteria:

* EPN with ≥ 2 other risk factors,
* \> 3 risk factors,
* bone invasion,
* immunosuppression due to immunosuppressive treatments (regardless of the reason). NI6. Patients with CEC presenting a single risk factor other than EPN; NI7. Patient with CEC and lymph node or distant metastasis; NI8. Patient with a history of cancer undergoing systemic and/or locoregional anticancer treatment;

Note: Local treatment of cutaneous keratoses with fluoropyrimidines is permitted outside the theoretical radiation field);

NI9. Patient with a contraindication to radiation therapy; NI10. Patient with a history of radiation therapy to the site of the lesion; NI11. Participation in another clinical trial that may interfere with the assessment of the primary endpoint; NI12. Patient under legal guardianship or conservatorship, or deprived of liberty; NI13. Pregnant or breastfeeding woman.

Where this trial is running

Le Puy-en-Velay, Auvergne-Rhône-Alpes and 27 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Cutaneous Squamous Cell CarcinomaSquamous cell carcinomas at high risk of recurrenceAdjuvant radiotherapySurveillancePeri Nervous System Sheathing
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.