Long lasting response to anti-PD-1 therapy of recurrent conjunctival squamous cell carcinoma - A case report and systematic review of the literature

Squamous cell carcinoma (SCC) are slowly progressing tumors which represent the most common malignancy of the ocular surface. The standard of care is surgical excision with wide margins combined with intra-operative cryotherapy. In advanced disease, ocular enucleation or orbital exenteration is recommended. Yet even with radical surgery, recurrence rates are high, ranging from 30 to 50%. Treatment options are limited in patients with advanced conjunctival SCC who do not qualify for or refuse surgery. We report a case of a 59-year-old woman with a poorly differentiated SCC of the conjunctiva (American Joint Committee on Cancer (AJCC) 7th edition T4N0M0) with tumor cell PD-L1 expression of 20%. Radical surgery with orbital exenteration was recommended but refused by the patient. As an alternative, she underwent repeated radiotherapy in order to control the multiple tumor recurrences. At the last tumor recurrence, 4 years and 9 months after initial diagnosis, re-irradiation was no longer possible. In analogy with cutaneous SCC, an anti-PD-1 therapy with cemiplimab was started. At 19 months of cemiplimab therapy, the patient presents with persistent stable disease and did not experience any immune related adverse events. The management of recurrent conjunctival SCC remains challenging. PD-1 targeting alone could be an effective strategy for the treatment of advanced conjunctival SCC with high PD-L1 expression or high tumor mutational burden in patients unsuitable or unwilling to undergo orbital exenteration or enucleation. Prospective trials and larger case series are needed to confirm this hypothesis.