What are the treatment options for leukoplakia?

Treatment of Oral Leukoplakia

Primary Treatment Recommendation

For oral leukoplakia, photodynamic therapy with aminolevulinic acid (ALA-PDT) is the preferred first-line treatment, particularly for extensive lesions or those in functionally sensitive areas, due to superior outcomes with minimal invasiveness and low disfigurement risk. 1, 2

Treatment Algorithm by Clinical Presentation

For Solitary or Localized Lesions

• Surgical excision or CO2 laser ablation are appropriate first-line options for isolated lesions, achieving complete response rates of 95-100% 3, 4
• Laser surgery demonstrates 29.3% recurrence and 1.2% malignant transformation rates, with excellent wound healing and minimal complications 4
• Radiotherapy can be considered as an alternative to surgery for localized disease 5

For Extensive or Multiple Lesions

• ALA-PDT is the treatment of choice for widespread disease where surgical approaches would cause significant functional impairment or disfigurement 1, 2
• Complete response rates range from 16.49% to 88.89%, with overall response rates of 50-100% 2
• Recurrence rates range from 0-41% over 1-30 months of follow-up 2

For Superficial White Lesions on Mobile Vocal Folds (Laryngeal Leukoplakia)

• Conservative management should be attempted first before biopsy, including avoidance of irritants and treatment of laryngeal candidiasis 5
• Biopsy is reserved for lesions that fail conservative therapy or demonstrate high-risk features (increased vascularity, ulceration, exophytic growth) 5

ALA-PDT Protocol

Preparation and Application

• Dissolve ALA to yield a 20% aqueous solution immediately before use 1, 2
• Apply photosensitizer to lesion surface after local anesthesia with 2% lidocaine or 4% prilocaine 2

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 to maintain effective intracellular oxygen concentrations 2
• Total light dose: 100 J/cm² 1, 2
• Treatment frequency: Once every 2-3 weeks depending on lesion healing 2

Post-Treatment Management

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

Response Assessment

• Evaluate treatment response 4 weeks after the last treatment session 2
• Response criteria: complete response (CR), partial response (PR), or no response (NR) 2

Management of ALA-PDT Side Effects

Common Adverse Reactions

• Mild to moderate pain, hyperemia, edema, erosion, ulceration, and bleeding are expected 1

Treatment of Side Effects

• 0.1% chlorhexidine gargling solution for routine post-treatment care 1
• Topical glucocorticoid preparations for inflammation 1
• Compound benzocaine gel for severe pain 1

Contraindications to ALA-PDT

Absolute Contraindications

• History of porphyria 2
• Coagulopathy 2
• Pregnancy 2
• Uncontrolled severe systemic disorders 2
• Allergy to light, porphyrin, or anesthesia agents 2

Alternative Treatment Options

Non-Surgical Medical Therapies

• Observation without intervention is acceptable for low-risk lesions 1
• Vitamin A and retinoids show significant clinical resolution rates compared to placebo, but high relapse rates and no proven benefit in preventing malignant transformation 6, 7
• Beta-carotene demonstrates clinical resolution but no prevention of malignant transformation 6, 7
• Chemoprevention should not be used with expectation of preventing malignant transformation, as evidence does not support this 2, 6

Other Surgical Options

• Cryosurgery is available but has significant limitations including postoperative pain, edema, and scarring 1
• Traditional excision and electrocauterization remain options but are more invasive than ALA-PDT 3, 1

High-Risk Features Requiring Aggressive Management

Non-Homogeneous Leukoplakia

• Non-homogeneous leukoplakia has significantly higher malignant transformation risk than homogeneous type and requires aggressive management 3, 2
• Lesions on non-keratinized epithelia (tongue mucosa) carry particularly high malignant transformation risk 4
• Consider vital tissue staining to detect abnormal epithelia before excision 4

Verrucous Lesions

• Verrucous leukoplakia (proliferative verrucous leukoplakia) demonstrates 83% recurrence rate with laser surgery, though most are ultimately controlled with subsequent procedures 8

Critical Pitfalls to Avoid

• Failing to protect treated areas from light exposure for the full 48-hour minimum after ALA-PDT is a common error that compromises outcomes 2
• Do not rely on chemoprevention to prevent malignant transformation, as no medical therapy has demonstrated this benefit in randomized trials 2, 6, 7
• Even after complete clinical resolution, regular long-term follow-up is mandatory as recurrence and malignant transformation remain risks regardless of treatment modality 9, 6, 8
• Recurrence rates after any treatment range from 7.7-38.1% for laser surgery and up to 67% for medical therapies 4, 9
• Malignant transformation occurs in 1.2-9% of cases even after successful treatment 4, 8