New guidelines from the American Academy of Dermatology strongly recommend the use of 5-fluorouracil (5-FU) or imiquimod for field treatment of actinic keratosis (AK). They also conditionally recommend the use of photodynamic therapy (PDT) and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.
These are two of the 18 recommendations made by 14 members of the multidisciplinary working group that met to bring together the first AAD guidelines on the management of AKs, which were published online April 2 in the Journal of the American Academy of Dermatology. The group, co-chaired by Daniel B. Eisen, MD, professor of clinical dermatology at the University of California, Davis, i Todd E. Schlesinger, MD, medical director of the Center for Dermatology and Laser in Charleston, SC, conducted a systematic review to address five clinical issues about the management of AK in adults. The questions were: what are the efficacy, effectiveness, and adverse effects of surgical and chemical treatments of the skin with AK; of agents applied topically by AK; of energy devices and other miscellaneous treatments for AK; and combination therapy for the treatment of AK? And what are the special considerations to keep in mind when dealing with AK immunocompromised individuals?
The working group then applied the Recommendation Classification, Evaluation, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence and formulate and classify clinical recommendations based on relevant randomized trials in the medical literature.
“As a participant in the working group, I was impressed with the level of care and detail and the involvement of relevant stakeholders, including a patient advocate, as well as the fact that the draft guidelines were passed on to AAD members in general. and evaluate all the comments that came in ” Maryam Asgari, MD, MPH, said in an interview the professor of dermatology at Harvard University, Boston. “The academy sought input from stakeholders and leadership in reviewing and renewing the guidelines. The AAD also ensured that the working group had minimal conflicts of interest in requiring that most experts convened have no relevant financial conflicts of interest. This may not be the case in a publication such as a systematic review, where no financial conflict of interest threshold is set for co-authorization. “
Of the 18 recommendations the working group made for patients with AK, only four were classified as “strong” according to the reviewed evidence, while the rest were classified as “conditional”.
The strongest recommendations include the use of UV protection, field treatment with 5-FU, field treatment with imiquimod, and the use of cryosurgery.
The first four conditional recommendations for patients with AK include the use of diclofenac, treatment with cryosurgery on CO2 laser ablation, aminolevulinic acid (ALA) –PDT of red light and incubation time of 1 to 4 hours of 5-ALA to improve complete elimination with PDT of red light. The working group also conditionally recommends the ALA daily light PDT that is less painful than the same effective one as the ALA red light PDA.
In the clinical experience of Catherine M. DiGiorgio, MD, which did not participate in the guidelines, PDT of natural light with ALA is a viable and cost-effective option. “Patients can come into the office, apply ALA and then go outside for 2 hours, not in direct sunlight, but in a shady area,” DiGiorgio, a dermatologist who practices in the Boston Center for Facial Rejuvenation. “This is a cost-effective treatment for patients who may not be able to afford some of the chemotherapy creams. I don’t think we’ve adopted much of the ALA daily light PDA here in the US.”
The working group noted that the current tirbanibulin ointment, a new microtubule inhibitor, was approved for the treatment of AKs on the face and scalp by the Food and Drug Administration after the guidelines were developed.
Several combination therapy trials were included in the review of the evidence, prompting several recommendations. For example, the working group conditionally recommends the combined burning of 5-FU and cryosurgery over cryosurgery only, based on moderate quality evidence, and conditionally recommends the combination of imiquimod and cryosurgery over low-evidence-based cryosurgery quality. In addition, the working group conditionally recommends the use of 3% diclofenac in addition to cryosurgery, favoring cryosurgery alone based on low-quality evidence, and conditionally recommends the use of imiquimod typically after ALA – PDT blue light, based on moderate -quality data.
“It was thought that additional treatment with imiquimod added costs and burdens to the patient, which negates much of the perceived convenience of using PDT as a stand-alone treatment modality and is not attenuated by the modest increase in injury reduction. “, wrote the authors.
The guidelines emphasize the importance of shared decision-making between patients and clinicians on the choice of therapy, a point that resonates with DiGiorgio. The success of a treatment may depend on whether a patient is willing to follow him, he said. “Some patients don’t want to do therapeutic topics like 5-FU. They prefer to go in and do cryotherapy. Others prefer not to go in and take the cream home and be treated.”
The assembly of the guidelines exposed certain gaps in the research, according to the working group. Of the 18 recommendations, seven were based on low-quality evidence and there was insufficient data to develop guidelines for the treatment of AK in immunocompromised individuals.
“I can’t tell you how many times we were on the committee and we said, ‘We need to do a randomized trial that analyzes it or compares it to the head one,'” Asgari said. “These limitations give guidance to researchers.” where the areas of study should go to help us respond to some of these management issues. “
She added that the new guidelines “give clinicians a leg up” when an insurer backs down the recommended treatment for AK. “It gives you a way to talk to insurers if you prescribe some of these treatments.”
The authors of the guidelines write that there is “a strong theoretical foundation for the treatment of AK to prevent skin cancers,” but acknowledge that only a few studies in the review “report the incidence of skin cancer as a measure.” result or have sufficient follow-up to feasibly measure the development of the carcinoma “. In addition, “more long-term research is needed to validate our current understanding of skin cancer progression from AKs to keratinocyte carcinoma.”
DiGiorgio thinks otherwise. “I think treating AKs prevents skin cancers,” he said. “We call them precancers while we treat our patients because we know that a certain percentage of them can become skin cancer over time.”
The study was funded with internal funds from the AAD. Asgari revealed that she is acting as a Pfizer researcher. Several other authors reported that they had financial disclosures.
DiGiorgio reported that he had no financial disclosures.
This article originally appeared on MDedge.com, which is part of the Medscape professional network.