Sequential Field Therapy in Actinic Keratosis: A Mechanism-Based Rationale for Complementary Treatment Strategies.

Area of Science:

• Dermatology
• Oncology
• Skin Cancer Research

Background:

• Actinic keratosis (AK) are common precursor lesions to cutaneous squamous cell carcinoma (cSCC).
• Chronic ultraviolet (UV) radiation exposure leads to field cancerization, necessitating broader treatment strategies beyond individual lesions.
• Understanding the field cancerization concept is crucial for managing AK and preventing cSCC progression.

Purpose of the Study:

• To review current field-directed therapies for AK, including their mechanisms, efficacy, and limitations.
• To propose a mechanism-based framework for sequential treatment strategies in AK management.
• To highlight the need for further research into optimal sequential treatment protocols.

Main Methods:

• Narrative review of existing literature on AK field-directed therapies.
• Analysis of mechanisms of action, efficacy, and tolerability of therapies like 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy, and tirbanibulin.
• Development of a framework for sequential treatment based on distinct biological targets.

Main Results:

• Available AK therapies utilize diverse, partially non-overlapping mechanisms including cytotoxicity, immune activation, and pathway inhibition.
• Complementary mechanisms support the rationale for sequential treatment regimens to address field cancerization heterogeneity.
• Limited direct clinical evidence exists for specific treatment sequences; proposed regimens are hypothesis-generating.

Conclusions:

• Sequential, mechanism-based field therapy presents a rational strategy for optimizing long-term AK control and managing field cancerization.
• Prospective comparative studies are essential to establish optimal treatment sequences, intervals, and patient selection criteria.
• Future research should focus on endpoints like sustained field clearance, recurrence reduction, and prevention of invasive cSCC.