Management of All Patients with Multiple Actinic Keratoses Requires Lifelong Follow-Up and Repeated Treatment Cycles: A 12-Year Prospective Observational Study of a Cohort of 81 Patients.

Abstract

Introduction: Many treatments for multiple actinic keratoses (mAKs) have been proven effective in clinical trials. However, there is a lack of evidence regarding the long-term impact of therapies on disease progression in patients with mAKs. This study aimed to investigate the long-term clinical trajectory of mAKs patients undergoing repeated topical interventions and to evaluate the clinical effectiveness of these treatments and patients' adherence to an extended follow-up protocol in a real-world setting.

Methods: We conducted a prospective follow-up of a cohort comprising 81 treatment-naïve mAKs patients from 2012 to 2023. Patients received examinations and, when necessary, interventions every 6 months. Instances of treatment cycle discontinuation and refusals to continue with specific therapies were systematically recorded. Descriptive statistics alongside the Student's t test were employed to evaluate improvements in the Physician Global Assessment (PGA) scores following treatment with the same medication.

Results: The average total number of medical examinations and treatments administered per patient was 23.0 ± 0.4 and 16.1 ± 2.4, respectively. Annually, the average number of examinations and treatments per patient was 1.9 ± 0.1 and 1.3 ± 0.2, respectively. We completed 539 (41.6%) treatment cycles using photodynamic therapy with red light and methyl aminolevulinate (MAL-PDT), 182 (14.0%) with diclofenac plus hyaluronate (DHA), 97 (7.5%) with imiquimod (IMI), 101 (7.8%) with 5-fluorouracil (5-FU), 25 (1.9%) with FU, and 353 (27.2%) with cryosurgery. PGA values indicated a statistically significant reduction following each treatment at the 30-day post-treatment mark; however, these values exhibited an increase by the 6-month follow-up visit. The rates of treatment cycle discontinuation were as follows: 28.0% with MAL-PDT, 22.0% with DHA, 27.8% with IMI, 22.8% with 5-FU, and 24.0% with FU. Refusal rates for subsequent treatment cycles with the same drug were documented as 32.7% for MAL-PDT, 17.6% for DHA, 24.7% for IMI, 21.8% for 5-FU, 20.0% for FU, and 12.2% for cryotherapy. Throughout the study duration, 223 cases of squamous cell carcinoma (SCC), 46 cases of basal cell carcinoma (BCC), and 4 malignant melanomas (MMs) emerged on the face or scalp, along with 71 SCCs, 64 BCCs, and 8 MMs in other body regions.

Conclusion: Immunocompetent patients with mAKs require lifelong follow-up accompanied by repeated treatment cycles, as the clearance rates, regardless of the degree achieved after a single treatment cycle, tend to be temporary. These patients are at a heightened risk of developing skin tumors.