Content » Vol 100, 100-year theme: Skin malignancies (June)


Biomarkers Predicting for Response and Relapse with Melanoma Systemic Therapy

Sarah J. Welsh, Pippa G. Corrie
DOI: 10.2340/00015555-3497


For all primary cutaneous squamous cell carcinomas (cSCCs), physical examination should include full skin examination, recording of tumour diameter and regional lymph-node–basin status. Surgery is the treatment of choice, with a minimal 5-mm margin. For elderly patients with well-differentiated tumours, other surgical modalities can be explored. Surgery for organ-transplant recipients should not be delayed. The issue with cSCC is identifying high-risk tumours with staging, as this may alter treatment and follow-up schedules. Adjuvant radiation therapy should be considered for incomplete resection, when re-excision is impossible or there are poor-prognosis histological findings. Recommendations are at least biannual dermatological surveillance for 2 years, but in elderly patients with small, well-differentiated tumours long-term follow-up is not always necessary. In case of positive lymph nodes, radical dissection is needed, with regional postoperative adjuvant radiation. Advanced cSCCs are defined as unresectable local, regional or distant disease requiring systemic treatment. Their only approved treat­ment is the PD-1 inhibitor, cemiplimab. Trials evaluating adjuvant or neo-adjuvant anti-PD-1 are ongoing. Platin-based chemo or anti-epidermal growth-factor–receptor therapies are possible second-line treatments. For transplant patients, minimizing immunosuppression and switching to sirolimus must be considered at first appearance of cSCC.


Systemic therapy options for melanoma patients are rapidly increasing. They offer life extension for many, but not all patients benefit. These high cost drugs also have complex, life-changing and potentially life-threatening side effects. Modern ‘Precision Medicine’ aims to personalize therapy for individuals and hence offer the opportunity to selectively treat only those expected to benefit from a particular therapy, while avoiding exposure to ineffective treatment in others. To date, the only validated predictive melanoma biomarker guiding treatment decisions is the BRAF gene mutation, although emerging modern technologies are identifying many more candidates whose clinical application have yet to be ascertained.

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