Two opposing views on how best to treat actinic keratosis

PARIS―In a joint, interactive session at the European Academy of Dermatology and Venereology (EADV) Congress in Paris last week, two physicians discussed the pros and cons of treatment for actinic keratosis.

David de Berker, M.D., of the University of Bristol, England, argued against treatment, while Günther Hofbauer, M.D., of Allergology and Dermatology, Switzerland, proposed another argument: actinic keratosis is a precancerous growth that should be treated. This article summarizes their positions.

“KEEP THINGS IN PROPORTION”
Dr. de Berker led the creation and rewriting of the actinic keratosis guidelines in the United Kingdom. “Today, I’ve been asked to propose the case that you don’t treat actinic keratosis ― which of course is an artificial thing ― but the idea here is to keep things in proportion.”

Actinic keratosis can be viewed and presented to patients in one of two ways: As sun damage spots or as precancers. Differences according to geographical and socio-economic factors are also evident, such as those seen in the slight differences between the European and United Kingdom actinic keratosis guidelines.

“The European guidelines are comprehensive and difficult to argue with,” Dr. de Berker said. “The UK guidelines tell you what the outcomes will be. Some will go away, they write, and some will possibly turn into cancer. [They] also take individual patient differences into account. You’re treating the patient and not the actinic keratosis.”

There may also be some issues with consent. Most actinic keratosis therapies, whether cryosurgery or cream application, have side effects and thus require consent, and most patients with actinic keratosis are elderly. De Berker presented an exemplary study in which 13 percent of patients with acute actinic keratosis were deemed to lack capacity for consent.

Patients aged 60-80 years old may also be less concerned about receiving treatment. Using insurance data from Kaiser Permanente, one study found that the vast majority of nearly 6,000 patients were middle-aged. This indicates that older patients are less likely to seek treatment than younger patients, Dr. de Berker said.

Cancer anxiety also influences treatment. “The way we have this discussion with [patients] will influence their response in terms of whether they’re choosing treatment or not.” When actinic keratosis is framed as a “precancer,” patients are more likely to choose treatment than if described as “spots” (Berry et al., 2017, JAMA Dermatology).

Grade and patient history should also be considered. “I’m looking for a nuanced approach in terms of how we interpret and treat people. It’s not purely, “this is the pathology and we treat it this way.” Medical concern is lower in patients aged over 80 years old with thin or lower-grade actinic keratosis and no previous skin cancer, and is higher in younger patients (younger than 60 years old) with multiple lesions, previous skin cancer, and a range of grades of actinic keratosis.

“SCC and AK are misnomers”

Actinic keratosis cells should be considered as cancer cells, even if only a few will go on to invade, Dr. Hofbauer said.

“Biologically speaking, there is no difference between an actinic keratosis cell and an invasive squamous cell carcinoma cell,” he said.

Behind clinically normal-looking skin is an active struggle and a delicate balance between mutated cells and normal differentiation. One publication (Martincorena et al., 2015, Science) found that about one quarter of skin on the upper eyelids harbours mutations in middle-aged people.

“I believe separating actinic keratosis from other skin cancers is fictitious because we don’t yet know which actinic keratosis are those that carry risks,” said Dr. Hofbauer referring to the treatment of mild hypertension. About 100 patients are treated to prevent just one myocardial infarction. “I realize if we call actinic keratosis ‘cancer,’ we may trigger fear and cost, but we should not obscure the terms by fearing the implications of it,” he said.

It is possible that actinic keratosis size and grade cannot, in fact, tell us which cells will progress to squamous cell carcinoma. Using these features to inform treatment was also called into question. While the common view is that there is an actinic keratosis growth from the bottom to the top and an increasing disruption to the epidermal architecture, Dr. Hofbauer suggests that growth towards the bottom may be the important factor in the transition from actinic keratosis to squamous cell carcinoma, regardless of the actinic keratosis size. One recent publication found that proliferation towards the bottom was mainly by thin, mild, ‘innocent-looking’ actinic keratosis (Schmitz et al., 2018, JDDG). “This would lead me to treat more actinic keratosis than fewer actinic keratosis,” he said.

Field treatment could be adopted to catch all early atypical cells, Dr. Hofbauer said. Actinic keratosis treatments typically have good cosmetic outcomes and longer remission.

Treatments such as soft radiotherapy for field cancerization result in younger-looking skin and effects that last for 10-20 years. Photodynamic therapy effects last around three years and treatment can be repeated. Medication such as nicotinamide can also be beneficial; nicotinamide reportedly repairs DNA damage, prevents squamous cell carcinoma and basal cell carcinoma, and reduces actinic keratosis (Chen et al., 2015, New England Journal of Medicine).

“One provocation would be to say:  Treat it before it happens,” Dr. Hofbauer said. He explains that it is not the actinic keratosis itself that is of interest, but the damage it represents, and that symptoms are not singular events but are linked together by an underlying driving force.

“The point is that we try to correct these risk factors in order to reduce the occurrence of these major events down the road,” he said. Early treatment is also cost-effective. Once squamous cell carcinoma occurs the cost of care remains high, Hofbauer said.

REFERENCES

de Berker, D. (2018). Treatment of actinic keratosis: When and why? Contra, The 27th European Academy of Dermatology and Venereology Congress, Paris, France, 15th September, 09:45 - 10:05.

Hofbauer, G. (2018). Treatment of actinic keratosis: When and why? Pro, The 27th European Academy of Dermatology and Venereology Congress, Paris, France, 15th September, 10:05 - 10:25.