What is the treatment for leukoplakia?

Treatment of Oral Leukoplakia

Photodynamic therapy with aminolevulinic acid (ALA-PDT) is the preferred first-line treatment for oral leukoplakia, particularly for extensive lesions or those in anatomically sensitive areas, due to its minimally invasive nature, high efficacy, and low risk of disfigurement. 1, 2

Treatment Algorithm

First-Line: ALA-PDT Protocol

Preparation and Application:

• Prepare 20% aqueous ALA solution immediately before use 1
• Apply local anesthesia with 2% lidocaine or 4% primacaine 1
• Apply photosensitizer directly to lesion surface 1

Treatment Parameters:

• Light source: Semiconductor laser at 630 nm ± 5 nm 1, 2
• Power setting: 100 mW/cm² 1, 2
• Irradiation protocol: 3-minute treatment sessions alternating with 3-minute rest periods (this maintains effective intracellular oxygen concentrations) 1
• Total light exposure dose: 100 J/cm² 1, 2
• Treatment frequency: Once every 2-3 weeks depending on lesion healing 1

Expected Outcomes:

• Response rates: 50-100% 1
• Complete response rates: 16.49-88.89% 1
• Recurrence rates: 0-41% over 1-30 months follow-up 1

Post-Treatment Management

Immediate Care:

• Prescribe topical 0.01% dexamethasone paste to reduce inflammation 1
• Prescribe 0.1% chlorhexidine gargling solution 1, 2
• Instruct patients to maintain oral hygiene and avoid irritating foods/drinks 1

Critical Light Protection:

• Prevent all light exposure to treated area for minimum 48 hours 1, 2
• For exposed sites like lips, extend light protection throughout entire treatment course 1

Pain Management for Severe Cases:

• 0.1% chlorhexidine gargling solution 2
• Topical glucocorticoid preparations 2
• Compound benzocaine gel for severe pain 2

Response Assessment

• Evaluate treatment response at 4 weeks after last treatment 1
• Response criteria: Complete response (CR), partial response (PR), or no response (NR) 1

Alternative Treatment Approaches

While ALA-PDT is preferred, traditional approaches include:

• Surgical excision (cold knife, laser ablation) 2, 3
• Cryosurgery (though associated with postoperative pain, edema, and scarring) 2
• CO2 laser ablation 2, 3
• Observation without intervention for low-risk lesions 2

Important Note: Surgical excision of non-homogeneous leukoplakia showed 74.8% disease-free status at 12-37 months follow-up, with 62.1% remaining disease-free at 3 years, though this represents older evidence 4

Risk Stratification

High-Risk Features Requiring Aggressive Management:

• Non-homogeneous leukoplakia (significantly higher malignant transformation risk than homogeneous type) 1, 3
• Presence of epithelial dysplasia on biopsy 4
• Lesions on tongue or floor of mouth (in certain populations) 5

Critical Pitfalls to Avoid

Common Errors:

• Failing to protect treated areas from light exposure for full 48 hours minimum is a frequent and serious mistake 1
• Using chemoprevention (vitamin A, beta carotene, retinoids) with expectation of preventing malignant transformation—this is not supported by evidence 1, 6
• Relying solely on observation without biopsy confirmation 7

Evidence Limitations:

• No randomized controlled trials demonstrate that non-surgical treatments (vitamins, beta carotene, NSAIDs, herbal extracts) prevent malignant transformation 6
• While some studies suggest vitamin A and beta carotene may achieve clinical resolution, relapse rates are high and adverse effects common 6
• Surgical interventions including laser therapy and cryotherapy have never been studied in RCTs with placebo/no treatment arms 6

Contraindications to ALA-PDT

Absolute contraindications include 8:

• History of porphyria 8
• Coagulopathy 8
• Pregnancy 8
• Uncontrolled severe systemic disorders (hypertension, heart disease, diabetes, severe liver/kidney damage, malignant tumors) 8
• Allergy to light, porphyrin, or anesthesia agents 8

Follow-Up Considerations

• Close long-term follow-up is required as risk of malignant transformation persists even after treatment 7
• No universal consensus exists on optimal follow-up duration or intervals 9
• Tobacco and alcohol cessation should be emphasized, though evidence for added value of specific treatments over primary prevention remains to be established 4