What are the treatment options for actinic keratosis?

Treatment Options for Actinic Keratosis

For actinic keratosis, use cryosurgery for isolated lesions or field-directed therapy with 5-fluorouracil, imiquimod, or tirbanibulin for multiple lesions, with UV protection mandatory for all patients. 1

Treatment Selection Algorithm

For Isolated Lesions (1-3 lesions)

Cryosurgery is the strongly recommended first-line treatment for isolated actinic keratoses. 1, 2

• Clearance rates range from 57% to 98.8% depending on freeze duration and follow-up 2
• Longer freeze times (>20 seconds) achieve 83% clearance versus 39% with shorter freeze times (<5 seconds) 2
• Double freeze-thaw cycles are more effective than single cycles (75% vs 68% response rates) 3
• Provides the convenience of single office visit treatment 2

Important caveat: For hyperkeratotic, thick, or ulcerated lesions, curettage with histological examination is preferred to rule out invasive squamous cell carcinoma, particularly on high-risk sites like the ear. 3

For Multiple Lesions (Field Cancerization)

Field-directed therapy is recommended when multiple actinic keratoses are present in a contiguous area. 1, 2

Strongly Recommended Field Therapies (in order of evidence strength):

1. Tirbanibulin 1% ointment (newest, most convenient option)

• Applied once daily for only 5 consecutive days to a 25 cm² treatment area 1
• Complete clearance rate: 49.3% at day 57 versus 8.6% with vehicle 1
• Partial clearance (≥75%): 72.2% versus 18.1% with vehicle 1
• Major advantage: Shortest treatment duration of all topical agents 1
• Adverse effects: Application site pruritus (9.1%) and pain (9.9%), with <1% experiencing severe reactions 1
• Strong recommendation with high certainty evidence 1

2. 5-Fluorouracil (5-FU)

• Multiple formulations available; 5% applied twice daily for 3-4 weeks reduces approximately 70% of actinic keratoses for up to 12 months 3
• Highest efficacy rating among established topical agents 2
• Strong recommendation with high certainty evidence 1
• Can be used on face, scalp, ears, neck, and lips 4

3. Imiquimod 5% cream

• Applied 2 times per week for 16 weeks to a 25 cm² treatment area 5
• Complete clearance: 44-46% versus 3-4% with vehicle 5
• Partial clearance (≥75%): 58-60% versus 10-14% with vehicle 5
• Strong recommendation with high certainty evidence 1
• FDA-approved for clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on face or scalp 5
• Important: Subclinical lesions may become apparent during treatment (48% of patients experience increase in visible lesions), but this does not predict poor response 5

Conditionally Recommended Field Therapies:

4. Photodynamic therapy (PDT)

• ALA-red light: 77.1% complete clearance at 12 weeks 2
• ALA-daylight: Less painful but equally effective as ALA-red light 2
• Conditional recommendation with moderate quality evidence 1, 2

5. Diclofenac 3% gel

• Moderate efficacy with low morbidity in mild actinic keratoses 1
• Conditional recommendation 1
• Limited long-term follow-up data 1

Combination Therapy Approaches

When monotherapy fails or for severe disease, combination approaches can be considered:

• 5-FU + Cryosurgery: Conditionally recommended over cryosurgery alone (moderate quality evidence) 2
• Imiquimod + Cryosurgery: Conditionally recommended over cryosurgery alone (low quality evidence) 2
• Diclofenac + Cryosurgery: Conditionally recommended AGAINST compared to cryosurgery alone 2

Practical combination strategy: One-week pretreatment with 0.5% fluorouracil cream before cryosurgery significantly reduces facial actinic keratoses compared to vehicle pretreatment. 4

Mandatory Adjunctive Therapy

UV protection is strongly recommended for ALL patients with actinic keratoses to prevent new lesions. 1, 2

• High-index sunscreen reduces appearance of new actinic keratoses 3
• Sun avoidance and physical protection are essential 5
• Patients should minimize or avoid natural or artificial sunlight (tanning beds, UVA/B treatment) during treatment 5

Site-Specific Considerations

Ear lesions require special attention:

• Higher risk of metastasis when squamous cell carcinoma develops at this site 2
• Risk of progression to squamous cell carcinoma ranges from <0.1% to 20%, with higher risk on the ear 2, 3
• Histological biopsy is essential for ear lesions due to higher transformation risk 3
• Curettage may be warranted for thicker lesions with suspicion of early squamous cell carcinoma 2

Critical Management Pitfalls

Recurrence rates are high: Actinic keratoses have recurrence rates estimated as high as 50% within the first year, necessitating ongoing monitoring and treatment. 2

Local skin reactions are expected and normal: Most patients experience erythema, flaking/scaling/dryness, and scabbing/crusting at application sites with topical therapies. 5 These reactions can extend beyond the application site and may require rest periods, but treatment can resume once reactions subside. 5

Treatment duration limits: Do not extend imiquimod treatment beyond 16 weeks or tirbanibulin beyond 5 days due to missed doses or rest periods. 5

Immunosuppressed patients: Safety and efficacy have not been established in immunosuppressed patients or organ transplant recipients; use with caution. 1, 5

Avoid internal use: Application in the vagina or other internal areas is contraindicated. 5 Female patients should take special care if applying near the vaginal opening due to risk of pain, swelling, and urinary difficulties. 5