What is the role of cryotherapy (cryosurgery) in treating actinic keratosis?

Cryotherapy for Actinic Keratosis

Cryotherapy is strongly recommended as an effective first-line treatment for individual actinic keratoses, with clearance rates ranging from 57% to 98.8% depending on freeze duration. 1

Mechanism and Efficacy

• Cryotherapy uses liquid nitrogen to freeze the epidermis and upper dermis, destroying abnormal keratinocytes in actinic keratoses 2
• Complete clearance rates vary significantly with freeze duration:
  • <5 seconds: 39% clearance
  • 5-20 seconds: 69% clearance

  • 20 seconds: 83% clearance 1, 3

• Overall efficacy in prospective studies shows a 67.2% complete response rate with a single freeze-thaw cycle 3
• Cryotherapy is particularly effective for thicker lesions, with 69% complete response compared to 52% with photodynamic therapy 1

Technique and Application

• Standard procedure involves applying liquid nitrogen until 1-2 mm of surrounding skin appears frozen 4
• A single freeze-thaw cycle is commonly used, though double freeze-thaw cycles may increase efficacy 1
• Temperature-controlled cryotherapy using devices with infrared sensors can achieve 100% short-term cure rates by maintaining precise temperatures (e.g., -5°C) 2
• Cryotherapy is primarily a lesion-directed treatment, best suited for few or isolated AKs rather than field treatment 1

Advantages and Patient Selection

• Cryotherapy is readily available, rapid, and can be performed in-office with minimal preparation 1
• It is particularly beneficial for:
  • Individual, well-defined lesions 1
  • Thicker, hyperkeratotic lesions 1
  • Patients who prefer a quick, single-session treatment 1
• Patient satisfaction ratings favor cryotherapy over CO2 laser ablation 1

Side Effects and Limitations

• Common side effects include:
  • Pain, stinging, and burning during treatment 3
  • Vesicle formation, erythema, and swelling immediately after treatment 4
  • Crusted eschar formation within days after treatment 4
  • Potential hypopigmentation or hyperpigmentation, especially in darker skin types 4
• Healing time typically requires 3-6 weeks, with longer healing times for longer freeze durations 4
• Recurrence rates increase over time: 2.1% at 1 year and 11.5% at 3 years 5

Combination Approaches

• Combining cryotherapy with topical treatments can enhance efficacy:
  • 5-FU plus cryosurgery is conditionally recommended over cryosurgery alone 1
  • Imiquimod plus cryosurgery is conditionally recommended over cryosurgery alone 1
  • Diclofenac combined with cryosurgery is not recommended over cryosurgery alone 1
• "Cryopeeling" uses diffuse cryotherapy across entire photodamaged areas rather than just on individual lesions 6

Comparison with Other Treatments

• Cryotherapy is conditionally recommended over CO2 laser ablation based on moderate quality evidence 1
• ALA-red light photodynamic therapy is conditionally recommended over cryosurgery alone, though cryotherapy causes less skin irritation immediately after treatment 1
• Cryotherapy is more effective than portable cryosystems (74% vs 62% efficacy) but with slightly lower tolerance 6

Follow-up and Monitoring

• Evaluation of treatment response typically occurs at 3 months post-treatment 3
• Incomplete responses may require repeat treatments at 3-week intervals 4
• Long-term monitoring is necessary due to increasing recurrence rates over time 5

Common Pitfalls and Caveats

• Underfreezing (<5 seconds) significantly reduces efficacy (only 39% clearance) 1, 3
• Overfreezing (>20 seconds) increases risk of scarring and pigmentary changes 4
• Cryotherapy does not address subclinical damage or field cancerization, limiting its use for patients with multiple lesions or extensive photodamage 1
• Cryotherapy should be avoided on eyelids, lips, nose, and ears due to potential complications 4