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

Background: Many treatments for multiple actinic keratoses (mAKs) have been proven efficient in clinical trials. However, there is a lack of evidence regarding the long-term impact of therapies on the disease progression in mAKs patients. Objectives: This study aims to investigate the long-term clinical trajectory of mAKs patients undergoing repeated topical interventions. It also assesses the clinical effectiveness of these treatments and patients' adherence to an extended follow-up protocol in a real-world context. 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 six 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 MAL-PDT, 182 (14.0%) with DHA, 97 (7.5%) with IMI, 101 (7.8%) with 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 six-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.