Laser-Activated Photodynamic Therapy (LA-PDT) for Actinic Keratosis
What Is Actinic Keratosis (AK) and Why Should You Treat It?
Actinic keratosis (AK) is a precancerous skin condition caused by long-term sun exposure. These rough, scaly patches appear on sun-exposed areas like the face, ears, scalp, arms, and hands. Though AKs are not cancer, they can turn into non melanoma skin cancer (NMSC) – Squamous Cell Carcinoma (SCC) or Basal Cell Carcinoma (BCC), if left untreated (1)(2). Treating them early helps prevent progression to skin cancer.
Actinic keratosis (AK) is best understood not just as a collection of isolated rough spots, but as a sign of wider sun damage affecting the entire “field” of skin.
Imagine your sun-damaged skin like a garden bed full of weeds. Some weeds are large and obvious (the thicker AK spots), while tens to hundreds of others are just starting to grow, only visible to the eye if you are kneeling directly in the dirt.
One treatment approach is to pluck out the biggest weeds—removing only the visible lesions. While this can provide short-term relief, it’s often a game of constant catch-up, as new weeds keep popping up from the same damaged soil.
The other approach is to treat the entire field, using a field treatment (conceptually analogous to using weed spray like roundup on the whole field instead of just pulling the larger weeds out) to clear both visible and invisible precancerous cells. While this broader treatment can cause more short-term skin irritation, it offers better long-term control by addressing the entire area of damaged skin, not just what you can see with the naked eye.
We can treat either the most visible AK or treat entire fields with laser assisted photodynamic therapy.
How Laser-activated Photodynamic Therapy (LA-PDT) works
Laser-activated Photodynamic Therapy (PDT) is an advanced skin treatment using a light-sensitive drug (photosensitizer, often ALA) activated by specific laser or LED light to destroy abnormal cells, effectively treating precancers (actinic keratosis), superficial skin cancers, acne, redness, and sun damage with better results and less downtime than traditional methods, combining laser’s precision with PDT’s cellular targeting. The laser ensures controlled light delivery, making it a powerful tool for cosmetic improvement and cancer treatment.
Figure 1. Normal Skin anatomy
Figure 2. Actinic Keratosis
Step 1)
Complete destruction of any precancerous lesions with extremely precise laser ablation.
Figure 2. Erbium laser ablation of AK. Note that AK still exists in microscopic areas and also down hair follicle
Precancer (AK) by definition exists in the uppermost layer of the skin (ie in the epidermis). This allows us to completely destroy any individual visible lesions by fully ablating the epidermis in this area. We can completely remove the epidermis with no chance of scarring. By this process we can theoretically entirely destroy all precancerous cells with just this method (and not need any additional steps). In practice, although precancer never invades beyond the Dermo-epidermal Junction (the tight membrane between the epidermis and the rest of the skin), precancerous cells do “invade” deeper into the skin via adnexal structures (eg. like hair follicles), which means that treating only the surface with just full ablative laser (or other far more basic techniques) isn’t as effective as the more advanced combination treatments that combine multiple steps.
Step 2: Fractional Laser Pre-Treatment to Enhance Absorption
A fractional ablative laser is then used to create microscopic channels into the skin. These “wells” help a medicated cream (in the next step) penetrate more effectively into the deeper skin and adnexal structures and also destroy some abnormal cells directly (4).
Step 3: Addition of a photosensitising drug to the surface of the skin – aminolevulinic acid (ALA) or Methyl Aminolevulinate (MAL, metvix)
A photosensitizing drug, like aminolevulinic acid (ALA), is applied as a cream to the skin, absorbed by abnormal cells over an hour.
Both aminolevulinic acid (ALA) and methyl-aminolevulinate (MAL, Metvix) are “pro-drugs.” After they are applied to the skin, they enter skin cells and are converted through the body’s normal haem (red-blood-pigment) pathway into a natural light-sensitive molecule called protoporphyrin IX (PpIX).
Sun-damaged, precancerous and cancer cells have a more active and “imbalanced” haem pathway than healthy skin. This makes them
- take up more drug ALA/MAL,
- make more of the upstream haem-pathway enzymes (ie convert more of the drug into PpIX)
- have less of the final enzyme (ferrochelatase) that converts PpIX into safe molecules that the light won’t activate.
As a result, PpIX builds up to much higher levels in actinic keratoses and non-melanoma skin cancers than in the surrounding normal skin.
Step 4.
The excess ALA is removed from the skin
We then shine the red treatment light onto the skin. This wavelength of light is designed to specifically interact with the PpIX. It will generate reactive oxygen species (ROS) that preferentially damage and destroy cancerous and precancerous cells, while normal skin (with much lower PpIX levels) is relatively spared.
Activation: A specific wavelength of laser or LED light is directed at the treated area, activating the drug.
Cell Destruction: This activation creates reactive molecules that selectively destroy the targeted damaged or cancerous cells while sparing surrounding healthy tissue.
What it Treats
Precancerous Lesions: Solar/actinic keratoses (AKs).
Superficial Skin Cancers: Like Bowen’s disease, basal cell carcinoma.
Cosmetic Issues: Redness, broken capillaries, sunspots, pigmentation, fine lines, and texture.
Acne: Moderate inflammatory acne, reducing oil production and inflammation.
Benefits of Laser-Assisted PDT
Synergistic Results: Combines laser’s ability to treat pigment/redness with PDT’s cellular targeting for superior outcomes.
Aesthetic Improvement: Better cosmetic results than any other treatment
Controlled Treatment: Lasers offer precise depth control for effective lesion clearance.
Minimal Downtime: Shorter recovery compared to some other treatments like strong creams.
Benefits of Laser-Assisted PDT Over Cream-Based Treatments
Shorter Healing Time Compared to Efudix or Aldara
Laser-assisted PDT generally causes less skin irritation and faster recovery than creams like 5-FU (Efudix) or imiquimod (Aldara). Most patients recover in 5–7 days, while creams can cause visible reactions for several weeks (9).
No Daily Application Required
Unlike creams, which require 4+ weeks of strict daily application, LA-PDT is performed in one session.. It’s ideal for patients with multiple AK spots or trouble following daily regimens (10).
High Clearance Rates for Actinic Keratoses
Clinical research shows that LA-PDT offers superior lesion clearance rates—up to 81%—compared to other therapies (11). The laser component significantly improves treatment depth and success (12).
Excellent Cosmetic Results After Healing
LA-PDT is gentle on surrounding healthy skin and avoids scarring or pigment changes. Many patients are highly satisfied with the appearance of their skin after healing (13).
References
- https://www.ncbi.nlm.nih.gov/books/NBK470553/
- https://www.cancer.org/cancer/skin-cancer/actinic-keratosis.html
- https://pubmed.ncbi.nlm.nih.gov/20646070/
- https://pubmed.ncbi.nlm.nih.gov/30657230/
- https://pubmed.ncbi.nlm.nih.gov/18248563/
- https://pubmed.ncbi.nlm.nih.gov/33199473/
- https://pubmed.ncbi.nlm.nih.gov/16766457/
- https://pubmed.ncbi.nlm.nih.gov/17417977/
- https://pubmed.ncbi.nlm.nih.gov/27989083/
- https://pubmed.ncbi.nlm.nih.gov/17156094/
- https://pubmed.ncbi.nlm.nih.gov/28614989/
- https://pubmed.ncbi.nlm.nih.gov/31741458/
- https://pubmed.ncbi.nlm.nih.gov/28994495/