From Acne to Skin Cancer, PDT Finds Expanding Role in Dermatology

Photodynamic therapy (PDT) has moved well beyond its origins in premalignant skin lesion management, demonstrating expanded clinical utility across oncologic, inflammatory, infectious, and cosmetic indications—though meaningful gaps in protocol standardization and evidence quality persist across several disease areas, according to a narrative review published in the International Journal of Molecular Sciences.¹

The findings arrive as PDT continues to gain traction among dermatologists seeking tissue-sparing, repeatable alternatives to surgery and systemic therapy. Despite a substantial body of evidence supporting its use in conditions such as actinic keratosis and basal cell carcinoma, current clinical guidelines have not fully kept pace with the therapy's expanding mechanistic and clinical footprint. A more integrated, mechanism-oriented framework, rather than purely disease-based classification, may better reflect how PDT should be positioned in modern treatment algorithms.

How PDT Works

PDT achieves its therapeutic effect through the interaction of 3 components: a photosensitizer, light of an appropriate wavelength, and tissue oxygen.

Together, these generate reactive oxygen species capable of inducing apoptosis, vascular disruption, and immune modulation within diseased tissue. In current dermatologic practice, topical precursors including 5-aminolevulinic acid and methyl aminolevulinate are most commonly used, with delivery formats ranging from conventional red-light LED protocols to daylight PDT and artificial daylight PDT, each carrying distinct tolerability and logistical profiles.

In clinical practice, methyl aminolevulinate (MAL)-PDT and 5-aminolevulinic acid (ALA)-PDT represent the 2 most widely used topical photosensitizer regimens, and while both rely on the same core photodynamic mechanism, they differ in formulation, tissue penetration, and practical application.² ALA, a low-molecular-weight compound, penetrates the stratum corneum readily and clears within 24 to 48 hours, limiting prolonged photosensitivity. MAL, a methyl ester derivative of ALA, exhibits greater lipophilicity and may achieve deeper tissue penetration, though it requires intracellular conversion back to ALA before becoming pharmacologically active. In actinic keratosis (AK), both agents demonstrated high complete response rates, with MAL-PDT achieving approximately 90% at 3 months and ALA-PDT reaching 84.5% to 87.6% at 6 months. The choice between them is often guided by lesion type, anatomical site, available light source, and patient tolerability. European Dermatology Forum guidelines have formalized this distinction, recommending MAL-PDT as a first-line field-directed option for grade I to II AKs while acknowledging ALA-PDT as an effective alternative depending on clinical context.

Strongest Evidence: AK and Bowen Disease

Among neoplastic and premalignant indications, PDT showed its strongest clinical foundation in AK and Bowen disease. Complete response rates of approximately 90% were reported with MAL-PDT for AK at 3 months, with cosmetic outcomes rated as "good" or "excellent" by 96% to 98% of investigators, comparing favorably with cryotherapy. In Bowen disease, initial cure rates ranged from 88% to 100% with ALA-PDT, and 12-month recurrence rates remained between 0% and 12%.

A More Selective Role in Skin Cancer

PDT's role was more selective in basal cell carcinoma. For superficial lesions, complete clearance rates at 3 months following MAL-PDT ranged from approximately 80% in difficult-to-treat cases to 97% in primary superficial tumors. In nodular basal cell carcinoma, response rates of 73% to 94% were observed with MAL-PDT, though surgery retained superiority for long-term tumor control. For squamous cell carcinoma, high recurrence rates of approximately 69% in nonsuperficial lesions precluded a recommendation for routine use as monotherapy.

Acne, Infections, and Cosmetic Use

Beyond oncology, evidence supported PDT's utility across a broader range of conditions. In acne, a systematic review of more than 4,300 patients across 82 studies confirmed consistent reductions in inflammatory lesions and sebaceous gland hyperactivity using 5-ALA or MAL-based protocols, though protocol heterogeneity remained a barrier to standardization. In infectious dermatology, human papillomavirus–related conditions, including common, plantar, and periungual warts, carried the strongest evidence base among viral indications. PDT also demonstrated activity against onychomycosis, cutaneous leishmaniasis, bacterial folliculitis, and MRSA, with the mechanistic advantage of biofilm disruption and low likelihood of microbial resistance. For photorejuvenation, the therapy induced dermal remodeling through controlled epidermal stress, with efficacy enhanced by combination strategies including microneedling and fractional carbon dioxide pretreatment.

What the Data Cannot Yet Show

As a narrative review, the study was subject to selection bias and did not employ a systematic grading approach across all indications. For conditions including Kaposi sarcoma, primary cutaneous lymphoma, and several infectious diseases, available data were largely derived from case reports and small series, limiting the generalizability of findings. Protocol variability across photosensitizer type, incubation duration, light source, and fluence further complicated cross-study comparisons. Pain, particularly in extensive field cancerization of the scalp and face, remained a practical barrier to wider adoption.

A Call for Mechanism-Oriented Guidelines

The authors called for a shift away from disease-label-based positioning of PDT toward algorithms that account for tissue characteristics, patient tolerability, and recurrence risk.

"Future guidelines should progressively move beyond a purely disease-centered positioning of PDT and adopt more mechanism-oriented algorithms, clarifying when PDT should be used primarily as a cytotoxic treatment, a field-directed immunomodulatory strategy, an antimicrobial approach, or a tissue-remodeling stimulus," the authors wrote.

Emerging directions included near-infrared photosensitizers, nanoparticle-based delivery platforms, theranostic systems, and combination strategies with immunotherapy and photothermal therapy, all of which may expand PDT's range in treating deeper lesions and more resistant disease.

References

1. Di Guardo A, Virone M, Gallo U, et al. Photodynamic therapy in dermatology. Int J Mol Sci. 2026;27(9):3960. doi:10.3390/ijms27093960
2. Morton CA, Szeimies RM, Basset-Seguin N, et al. European Dermatology Forum guidelines on topical photodynamic therapy 2019 part 1: treatment delivery and established indications — actinic keratoses, Bowen's disease and basal cell carcinomas. J Eur Acad Dermatol Venereol. 2019;33(11):2225-2238. doi:10.1111/jdv.15783