Implications for clinical practice

Spontaneous regression rates

As discussed in the background section, the prognosis of AKs without treatment is confounded by the spontaneous regression rate. A study from Queensland28 reported a spontaneous regression rate of 85% (95% CI: 75-96%) in subjects with prevalent AK (AK diagnosed on a person during their first exam) and 84% (95% CI: 72-96%) in persons with incident AK (AK appearing for the first time during the study).

We (PP and SC) compared the efficacy of 5% 5-FU with a range of plausible spontaneous regression rates of AK.39 While we could not pinpoint the exact threshold of spontaneous regression rate above which 5-FU would be less effective than no therapy, we find it intriguing that the natural regression rate of AK can be such that the efficacy of a therapeutic modality may appear to be less than no therapy. Assuming the efficacy of 5-FU ointment to be 79%, we calculated that if the spontaneous AK regression rates were above 75%, no therapy may be better than using 5-fluorouracil.

Of note, standard care is to always treat AK because we cannot predict which cases will resolve spontaneously and which will progress to cancers. To explore this idea more fully, we propose future studies to directly compare three strategies: 5-FU, cryotherapy and no therapy.

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