Dr. Sondak discusses the features that prompt consideration of systemic therapy in patients with recurrent, advanced, or metastatic cSCC. He emphasizes that no single factor, such as size, histology, or location, defines unresectability; rather, it is a combination of surgical feasibility and patient goals. Red flags include signs of major nerve involvement, regional nodal spread, and tumors where surgery would result in significant morbidity. He stresses that although almost any tumor can technically be removed, the morbidity of radical surgery and availability of effective systemic alternatives must be weighed carefully.
Dr. Zager then explains the mechanism of action of PD-1 and PD-L1 inhibitors in cSCC, linking the disease’s high tumor mutation burden driven by cumulative UV exposure to its robust responsiveness to immunotherapy. He contrasts immunotherapy’s durable responses with the shorter-lived and more toxic profile of chemotherapy, particularly in the elderly population that commonly presents with this disease.
