What are the treatment options for oral leukoplakia?

Treatment of Oral Leukoplakia

Primary Treatment Recommendation

Photodynamic therapy (ALA-PDT) is recommended as the preferred treatment for oral leukoplakia, particularly for extensive lesions or those located in areas with underlying functional structures, due to its minimally invasive nature, efficacy, and low risk of systemic side effects and disfigurement. 1, 2

Treatment Algorithm

First-Line Approach: ALA-PDT Protocol

Preparation and Application:

• Dissolve aminolevulinic acid (ALA) to yield a 20% aqueous solution immediately before use 2
• Apply the photosensitizer to the lesion surface after local anesthesia with 2% lidocaine or 4% primacaine 1

Treatment Parameters:

• Use a semiconductor laser light source at 630 nm ± 5 nm 1, 2
• Power setting: 100 mW/cm² 1, 2
• Irradiation protocol: 3-minute sessions followed by 3-minute rest periods to maintain 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 range from 50% to 100%, with complete response rates of 16.49% to 88.89% 1
• Recurrence rates range from 0% to 41% over 1-30 months of follow-up 1

Alternative Approaches When ALA-PDT Is Unavailable

Observation Without Intervention:

• Appropriate for homogeneous leukoplakia without high-risk features 2, 3
• Long-term observation shows 32.5% of lesions may reduce or disappear without treatment, particularly when irritation is removed 3
• However, cumulative malignant transformation rate reaches 11.6% at 10 years without intervention 3

Surgical Methods:

• Traditional excision, electrocauterization, CO2 laser ablation, or cryosurgery 1, 2
• These are less feasible for extensive lesions or those at anatomical sites with underlying functional structures 1
• Significant limitations include postoperative pain, edema, and considerable scarring 1, 2

Medical Treatments (Limited Evidence):

• Vitamin A and retinoids may achieve clinical resolution but have high relapse rates and no proven benefit in preventing malignant transformation 4, 5
• Beta carotene shows similar limitations 5
• Topical bleomycin has been tested but lacks evidence for cancer prevention 5, 6

Post-Treatment Management

Immediate Post-Treatment Care:

• Prescribe topical 0.01% dexamethasone paste and 0.1% chlorhexidine gargling solution to reduce inflammation 1
• Instruct patients to keep mouth clean and avoid irritating foods and drinks 1, 2
• Critical: Prevent light exposure to treated area for at least 48 hours; extend throughout entire treatment course for exposed sites like lips 1, 2

Managing Adverse Reactions:

Common reactions (mild to moderate pain, hyperemia, edema, erosion, ulceration):

• Mild cases heal spontaneously without treatment 1
• Severe cases: 0.1% chlorhexidine gargling solution 1, 2
• Topical glucocorticoid preparations (prednisolone solution) 1, 2
• Compound benzocaine gel for severe pain 1, 2
• For extensive erosion/ulceration: Short-term (3-5 days) oral prednisone acetate 15-30 mg 1

Light sensitivity reactions (maculae, papules, blisters, erosion):

• Prevention: Strict avoidance of strong sunlight and indoor light, use protective equipment (parasol, mask) 1
• If reactions occur: Exit lighted area immediately, oral antihistamines (cetirizine), 0.1% chlorhexidine gargling, topical glucocorticoid dressing 1

Response Assessment

Evaluation Timeline:

• Assess treatment response 4 weeks after the last treatment 1

Response Criteria:

• Complete response (CR): Visible lesion disappears 1
• Partial response (PR): ≥20% reduction in size 1
• No response (NR): <20% reduction or increase in size 1

Critical Pitfalls to Avoid

High-Risk Features Requiring Aggressive Management:

• Non-homogeneous leukoplakia has significantly higher malignant transformation risk than homogeneous type 1, 7, 3
• Tongue location carries increased cancer risk 3
• Higher degrees of epithelial dysplasia predict malignant transformation 3

Common Errors:

• Failing to protect treated areas from light exposure for full 48 hours minimum 1, 2
• Using chemoprevention (vitamin A, retinoids, beta carotene) with expectation of preventing malignant transformation—no evidence supports this 4, 5
• Assuming surgical excision prevents cancer—this has never been proven in randomized trials 1, 5

Evidence Limitations

The current evidence base has significant gaps: standardized protocols, adequate sample sizes, and long-term follow-up data for ALA-PDT are still needed 1. No treatment has been proven to prevent malignant transformation 4, 5. Despite these limitations, ALA-PDT represents the most promising approach given its favorable risk-benefit profile compared to surgical alternatives 1, 2.