Safety and Efficacy of Aminolevulinic Acid 20% Topical Solution Activated by Blue Light for Facial Cutaneous Squamous Cell Carcinoma in situ

May 2026 | Volume 25 | Issue 5 | 454 | Copyright © May 2026


Published online April 30, 2026

Mark S. Nestor MD PhDa,b,c, Aysham Chaudry DOa, Robert J. Vanaria BSa,d, Vishnu Bhupalam BSa,e

aCenter for Clinical and Cosmetic Research, Aventura, FL
bDepartment of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL
cDepartment of Surgery, Division of Plastic Surgery, University of Miami Miller School of Medicine, Miami, FL
dHackensack Meridian School of Medicine, Nutley, NJ, USA
eUniversity of Central Florida College of Medicine, Orlando, FL

Abstract
Background: Squamous cell carcinoma in situ (isSCC) is an early-stage cutaneous malignancy that requires effective treatment to prevent progression to invasive SCC. Aminolevulinic acid photodynamic therapy (ALA-PDT) is a noninvasive treatment that selectively targets neoplastic cells. This study evaluated the effectiveness, safety, and tolerability of ALA-PDT for the treatment of patients with facial isSCC.
Methods: In this single-center, investigator-initiated, open-label study (NCT06159842), adult patients with biopsy-confirmed facial isSCC received 2 treatments with 20% ALA and blue light exposure, administered 28 days (± 3 days) apart. Lesions were excised for histopathological assessment 8 weeks after the second treatment. The primary endpoint was complete histological clearance at the end of treatment (EOT). Secondary outcomes included clinical clearance and tolerability.
Results: A total of 32 patients were enrolled in this study, of whom 30 completed the study. All patients achieved complete histological clearance at EOT. Clinical clearance was observed in all patients prior to excision, with 40% achieving clearance by day 49 and the remainder by day 69. Local skin reactions, including erythema and flaking, were mild and resolved over time. Only 1 patient experienced temporary hyperpigmentation. Pain scores remained low (mean, 2.71/10). Two patients reported adverse events considered unrelated to treatment.
Conclusions: ALA-PDT achieved 100% complete histological and clinical clearance with minimal adverse effects, demonstrating its potential as a safe, effective, and cosmetically favorable alternative to surgical excision for the treatment of facial isSCC. Further studies are needed to assess long-term recurrence rates and broader applications.

INTRODUCTION

Nonmelanoma skin cancer is the most common form of cancer, with cutaneous squamous cell carcinoma (SCC) accounting for more than 20% of all skin cancers.1,2 Although historically less prevalent than basal cell carcinoma (BCC), SCC carries a significant risk of metastasis and mortality and a poor prognosis.3-6 Unfortunately, the incidence of SCC continues to rise, as observed in the Rochester Epidemiology Project conducted by the Mayo Clinic, which reported a 263% increase in the incidence of SCC between studies spanning the years 1976 to 1984 and 2000 to 2010.7 In fact, recent studies have indicated that in areas of high sun exposure such as South Florida, SCC and its subtypes are significantly more prevalent than BCC.8,9 Ultraviolet radiation exposure, especially ultraviolet A, is the primary risk factor for developing SCC; other risk factors include advanced age, fair skin, carcinogen exposure, chronic inflammation, and immunosuppression.10,11 SCC often arises from precancerous lesions, including actinic keratoses (AKs) and SCC in situ (isSCC), also known as Bowen disease.12 isSCC is a common superficial cutaneous malignancy with a reported rate of progression to invasive SCC of 3% to 5%.13 Treatment of isSCC is crucial to prevent such progression.

Histopathological examination is the mainstay for the diagnosis of SCC, with certain histological features - such as poor differentiation, tumor depth >2 mm, and perineural invasion - indicating a higher risk for recurrence and metastasis.11,14 The gold standards for the treatment of SCC are Mohs micrographic surgery (MMS), surgical excision, and radiation therapy (RT). MMS or RT may be indicated for high-risk SCC and SCC located

Keywords: Squamous cell carcinoma in situ, Aminolevulinic acid photodynamic therapy, histological clearance, blue light exposure, erythema, skin cancer
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