Systemic Therapy as an Alternative to Surgery for Skin Cancer

Skin cancers, including basal cell carcinoma (BCC) and melanoma, can also develop in sensitive areas such as the eyelids, posing unique challenges for treatment. Surgical removal is often the preferred method for excising tumors in these regions, especially given the proximity to the eye and the importance of both functional and aesthetic outcomes.

BCC is the most prevalent form of skin cancer in Germany, with nearly 160,000 new cases diagnosed annually. While BCC is generally less aggressive than melanoma, it can still manifest on the eyelids, where approximately 2% of these tumors appear. Professor Vinodh Kakkassery, head of the ophthalmology department at Chemnitz Hospital, recently highlighted at a press conference organized by the German Ophthalmological Society (DOG) that complete surgical removal remains the gold standard for treatment.

According to Kakkassery, effective surgical techniques can reduce the recurrence rate of eyelid BCC from 30% to just 1%. However, in cases where the tumors are large or aggressive, surgery might not be viable, as it could necessitate the removal of the eye itself. In such instances, systemic therapies utilizing Hedgehog inhibitors can be administered, either as a primary treatment or as a neoadjuvant therapy to shrink the tumor before surgery, aiming to preserve healthy tissue or the eye.

Hedgehog inhibitors like Vismodegib and Sonidegib are given orally and have shown promise in treating advanced BCC, particularly when surgical or radiation options are unsuitable. A literature review published in 2024 in the journal Ophthalmology reported that the majority of patients treated with Vismodegib for orbital BCC experienced significant tumor reduction, with up to 88% achieving complete remission initially. However, despite these positive outcomes, a considerable number of patients ultimately required surgery, with up to 80% needing surgical intervention and about 23% facing eye removal. Side effects from the treatment were prevalent, including muscle cramps, hair loss, weight loss, fatigue, and changes in taste.

A separate study published in 2023 in Dermatology and Therapy evaluated Sonidegib in 16 patients with locally advanced periorbital BCC. The results indicated that 56% of tumors responded completely, while 25% showed partial response. Although side effects were common, they were generally milder compared to those experienced with Vismodegib, leading to fewer therapy discontinuations.

Professor Kakkassery emphasized the potential benefits of topical Hedgehog inhibitors designed for application on the eyelids, suggesting that such localized therapies could maximize efficacy while minimizing systemic side effects.