What are the adjuvant therapy options for a patient with local recurrence of conjunctival melanoma after surgical excision?

Adjuvant Therapy Options for Local Recurrence of Conjunctival Melanoma After Surgical Excision

For local recurrence of conjunctival melanoma after surgical excision, re-excision should be combined with adjuvant therapy using cryotherapy, brachytherapy (for localized bulbar lesions), or topical mitomycin C 0.04% (for extensive/multifocal disease), as surgical excision alone results in unacceptably high recurrence rates. 1, 2

Primary Treatment Approach

Re-excision is the foundation of treatment for local recurrence, using a minimal touch technique with microscopically controlled margins 1. However, surgery alone is insufficient—adjuvant therapy is mandatory to reduce the high propensity for subsequent recurrence 1, 2.

Adjuvant Therapy Selection Algorithm

For Localized Bulbar Conjunctival Lesions:

• Adjuvant brachytherapy is the preferred option for circumscribed lesions on the bulbar conjunctiva 1
• This provides targeted radiation to the tumor bed while sparing surrounding structures 1

For Non-Bulbar, Extensive, Diffuse, or Multifocal Disease:

• Topical mitomycin C (MMC) 0.04% four times daily is recommended 1, 3
• Standard regimen: 28 days as primary treatment or 7 days as adjuvant therapy following excision and cryotherapy 3
• Alternative regimen: Two to three 1-week cycles of MMC 0.04% four times daily 4
• MMC demonstrates effectiveness for superficial tumors but has limitations for deeper subconjunctival involvement 3

Cryotherapy:

• Should be combined with surgical excision as standard adjuvant treatment 1, 2
• Particularly effective when used in combination with other modalities 2

Proton Radiotherapy:

• Reserved for extensive tumor growth not amenable to brachytherapy 1

Novel and Emerging Adjuvant Options

• Topical interferon alpha-2b immunotherapy for immunomodulation 1
• Topical VEGF inhibitors to target tumor angiogenesis 1
• Selective BRAF inhibitors (or combination with MEK inhibitors) for tumors with documented BRAF mutations—this represents personalized targeted therapy 1

Evidence Supporting Combined Approach

The evidence strongly demonstrates that excision alone results in high recurrence rates. A long-term study showed that tumors treated with excision plus adjuvant therapy had significantly lower cumulative probability of local relapse compared to excision alone 2. Specifically:

• Unfavorable tumor locations (palpebral conjunctiva, fornix, caruncle, corneal stroma, eyelid) and higher TNM grade showed higher recurrence with excision alone 2
• When MMC was used as adjuvant to excision and cryotherapy, localized primary lesions showed 0% recurrence at mean 56.8 months follow-up 4
• However, 40% of patients experienced recurrence when MMC was used as adjuvant in one series, with recurrences occurring at mean 4.3 years 3

Critical Pitfalls to Avoid

• Never perform excision alone for recurrent conjunctival melanoma—this results in unacceptably high re-recurrence rates 2
• Recognize MMC limitations for deep disease: Histopathologic studies show MMC is most effective for superficial tumors; subconjunctival recurrences can occur with sparing of the epithelium and superficial lamina propria 3
• Monitor for subconjunctival recurrence: Even with adjuvant therapy, 2 of 5 patients (40%) developed subconjunctival recurrence in one series, emphasizing the need for vigilant long-term surveillance 3
• Expect transient keratoconjunctivitis during MMC treatment—this occurs in all patients but is manageable 3

Mandatory Follow-Up Structure

• Quarterly examinations for the first 5 years are essential 1
• Lifelong surveillance is required due to unpredictable tumor behavior 2
• Psycho-oncological healthcare should be integrated into the follow-up program 1
• Median follow-up in long-term studies was 13.1 years, reflecting the prolonged risk period 2

Treatment Resistance Considerations

• Nodular melanoma may be resistant to MMC chemotherapy 3
• For MMC-resistant or deeply invasive recurrences, consider proton radiotherapy or enrollment in clinical trials for targeted therapies 1
• Orbital exenteration may be necessary for aggressive subconjunctival recurrences not controlled by conservative measures 3