Welcome to this month's journal review — we're covering the June 2026 issue of the Journal of the American Academy of Dermatology, and this episode is devoted entirely to one substantial CME piece: Part Two of a two-part continuing education series on photodynamic therapy, or PDT, in dermatology. This is a review article, so we won't be walking through a methods-results-limitations arc the way we would for an original study — instead I'll synthesize the evidence base the authors pulled together, organized by indication, roughly in the order of supporting evidence they present.

Let's start with the framing. PDT combines a photosensitizer — most commonly five-aminolevulinic acid, or ALA, or its methyl ester, methyl aminolevulinate, MAL — with a light source, typically red or blue light, to generate reactive oxygen species that drive apoptosis, vascular injury, and immune modulation in target tissue. In the US, the approved formulation is twenty percent ALA with blue light for actinic keratoses, and separately a ten percent nanoparticle ALA formulation, marketed as Ameluz, with red light, also for actinic keratoses. In Europe, sixteen percent MAL with red light carries approval for the same indication. Everything else the authors discuss — and there's a lot — is off-label, which is really the organizing principle of this review: they've ranked dermatologic applications of PDT by level of evidence, from actinic keratoses at the top down through basal cell carcinoma, squamous cell carcinoma in situ, acne, and then further down the list into port wine stains, infections, photoaging, actinic cheilitis, mycosis fungoides, rosacea, alopecia areata, and extramammary Paget disease.

Given who's listening, I'll spend real time on the indications most relevant to a Mohs and oncologic dermatology practice — actinic keratoses, basal cell carcinoma, and squamous cell carcinoma in situ — and move a bit faster through acne, which is the last indication with substantial reported detail in this excerpt.

Starting with actinic keratoses — the original 1999 FDA approval indication. The foundational phase two and three trials using twenty percent ALA with blue light showed clearance rates in roughly the high seventies to high eighties percent range on the face and scalp, and somewhat lower, around seventy to eighty percent, on the upper extremities — a site-dependent pattern that's held up across the subsequent literature. The evidence here is about as strong as it gets in this space, level one-A, with multiple randomized trials and meta-analyses. A few comparative points worth flagging for practice: three separate meta-analyses found PDT outperforms cryotherapy. Two found ALA-PDT with red light beats both imiquimod and topical fluorouracil, though interestingly MAL-PDT with red light did not show that same superiority over those agents — a real formulation-dependent distinction worth remembering. Three meta-analyses also found the nanoparticle BF-200 ALA formulation outperforms MAL. And daylight-mediated MAL-PDT performed comparably to conventional lamp-based PDT for actinic keratoses, with fewer adverse events and better patient satisfaction — a nice option to have for patients who don't tolerate a clinic-based light session well. On technique, occlusion during photosensitizer incubation improves penetration and is actually indicated for certain formulations, and simple mechanical prep — gentle curettage or gauze abrasion, or alternatively a week of twice-daily urea keratolytic pretreatment — measurably improves outcomes by helping photosensitizer penetrate the keratotic surface.

Moving to basal cell carcinoma, which is obviously closer to home. The key framing here, consistent with the 2023 European Dermatology Forum consensus, is that PDT is a reasonable option specifically for superficial and low-risk nodular basal cell carcinomas — small, under two centimeters, well-demarcated, treatment-naive lesions. Six meta-analyses support efficacy at level one-A evidence. One phase three trial using two weekly sessions of either MAL or the nanoparticle ALA formulation with red light achieved complete response in more than nine in ten patients with nonaggressive basal cell carcinoma, with no meaningful difference between the two photosensitizers. Another randomized trial using MAL with a higher-fluence red light protocol reported clearance in the low-to-mid nineties percent range at three months, but — and this is the number that actually matters for counseling — recurrence rates climbed to roughly nine percent at one year and twenty-two percent at five years. That's a meaningful attrition curve to keep in mind when a patient asks about durability. Across four additional meta-analyses, PDT performed comparably to cryotherapy and fluorouracil in complete response rates, but consistently underperformed surgery, with higher recurrence — the tradeoff being that PDT reliably delivers superior cosmetic outcomes. The authors are explicit and this bears repeating clearly: PDT should not be used for infiltrative or high-risk basal cell carcinoma, defined the way we'd expect — H-zone locations like eyelid, nose, ear, or lip, lesions two centimeters or larger, or a recurrence history. Curettage before treatment is a reasonable adjunct.

For cutaneous squamous cell carcinoma in situ, or Bowen disease, the evidence is again level one-A. A meta-analysis reported clearance rates around seventy-seven percent at twelve to eighteen months, rising slightly to about eighty-two percent at eighteen to twenty-four months, then falling to around two-thirds beyond two years — so durability decays over time, which is worth factoring into follow-up intervals. Head-to-head, ALA-PDT modestly outperformed MAL-PDT, roughly eighty-one versus seventy-one percent clearance. Compared with cryotherapy and fluorouracil, PDT again showed higher response rates, lower recurrence, and better cosmesis. But compared with surgery, PDT clearly loses on clearance — eighty-two percent versus ninety-seven percent at one year — reinforcing that this is a tool for poor surgical candidates, multiple or large lesions, or cosmetically sensitive sites rather than a first-line alternative to excision when surgery is feasible. As with actinic keratoses, gentle debridement of hyperkeratotic scale before treatment improves photosensitizer uptake.

Rounding out the detailed portion of this review, acne gets substantial coverage as a level one-A indication, though it's further afield from oncologic practice. PDT — using ALA, MAL, indole-three-acetic acid, indocyanine green, or methylene blue paired with red or blue light — reduces inflammatory and noninflammatory lesion counts and sebum output, with reductions in total lesion count reported up to around eighty percent at three months in some protocols. Meta-analytic data suggest no real efficacy difference across light source types — red light, intense pulsed light, pulsed dye laser, or nonablative fractional laser all performed similarly. Comparative trials found ALA-PDT with red light roughly comparable to six months of low-dose isotretinoin for moderate-to-severe acne, but with faster onset of visible improvement, and superior to a combination of topical adapalene and oral doxycycline over six weeks. Recurrence after PDT was numerically lower than after isotretinoin in one trial — about twenty-four percent versus thirty-eight percent at six months — though the authors note this difference did not reach statistical significance, so it shouldn't be oversold. The main practical limitation flagged is tolerability: treatment sessions are often quite painful due to the inflammatory response, though longer-incubation daylight protocols appear to ease that burden.

So, pulling this together for practice. This is a review, not a new trial, so there's no primary dataset to critique for bias — the value here is in the synthesis and the dosing tables the authors provide alongside it. For a Mohs surgeon, the genuinely practice-relevant takeaways are these: PDT remains a well-supported, guideline-endorsed option for field-directed actinic keratosis treatment and for carefully selected low-risk superficial or nodular basal cell carcinomas and squamous cell carcinoma in situ — but the recurrence data, especially that climb from single digits at one year to over twenty percent by five years for basal cell carcinoma, means it should be framed to patients as a lower-morbidity alternative with a real efficacy tradeoff, not as an equivalent substitute for surgical clearance. It's most defensible in poor surgical candidates, multiple or field-cancerized areas, or cosmetically sensitive sites, with appropriate discussion of long-term recurrence risk and a monitoring plan. The formulation-specific nuances — nanoparticle ALA outperforming MAL, ALA outperforming MAL for Bowen disease, MAL not beating imiquimod or fluorouracil the way ALA does — are worth knowing if you're the one selecting or discussing protocols, but none of this changes the core surgical decision-making for high-risk or infiltrative disease, where PDT simply has no role. The acne and cosmetic indications are interesting context for a full-spectrum dermatology practice but not directly actionable for an oncology-focused Mohs practice.

That's the full article for this episode. Thanks for listening, and I'll see you next month for the next round of journal review.