Topical interventions (eg, 5-FU, ingenol mebutate, and diclofenac) improve outcomes after cryosurgery for actinic keratosis

Reference

Heppt MV, Steeb T, Ruzicka T, Berking C. Cryosurgery combined with topical interventions for actinic keratosis: a systematic review and meta-analysis. Br J Dermatology 2019;180(4):740-748.

Synopsis

The authors of this well-conducted meta-analysis screened 1758 studies and ultimately included only 9 of them. Limitations include the often poor descriptions of the studies, with unclear accounts of randomization or allocation concealment, and the failure to mask the participants in 5 trials and the outcome assessors in 2 trials. The topical interventions applied after cryosurgery for actinic keratosis included imiquimod in 4 studies, ingenol mebutate in 2 studies, diclofenac 3% in 2.5% hyaluronic acid in 1 study, 5-fluorouracil 0.5% cream in 1 study, and photodynamic therapy with aminolevulinic acid (ALA-PDT) in 1 study. The overall likelihood of complete lesion clearance when combining all 9 studies was greater with the addition of topical therapy (relative risk [RR] 1.74; 95% CI 1.25 - 2.43). Applied to a base rate of complete lesion clearance of 46% with cryosurgery alone, the addition of a topical intervention would increase the rate to 79%. A similar pattern was seen for partial clearance in 3 studies with 421 patients (RR 1.64; 0.88 - 3.03). There was no difference in withdrawals, indicating good tolerability. However, there was substantial heterogeneity between studies (I2 = 73%). Individual studies of diclofenac, 5-FU, and ingenol mebutate showed significant benefit consistent with the overall effect, while imiquimod and ALA-PDT did not, but sample sizes for most studies were small