Amaral T, et al. - Researchers investigated the patient and tumor characteristics along with treatment patterns among patients diagnosed with advanced cutaneous squamous cell carcinoma (acSCC; stages III and IV). They assessed 195 patients with acSCC (median age at time of advanced disease diagnosis: 78 years) who were diagnosed and treated at their center from 2011 to 2018. The tumors were identified as resectable in 145 patients. This group exhibited the median overall survival (mOS) of 59 months, which is significantly higher than the mOS in patients with an inoperable tumor. They observed a statistically significant better survival for patients receiving immunotherapy (n = 20) vs those treated with other systemic therapies (n = 37; mOS not reached vs mOS: 22 months (95% CI: 6.5–43.5), P = 0.034). A combination of surgery and radiotherapy provided better outcomes compared with radiotherapy alone or best supportive care for patients without systemic therapy. Surgical complete resection should be the first therapeutic option for patients with acSCC. For patients with inoperable tumour, first-line immunotherapy should be preferably considered. These findings support surgical complete resection as the first therapeutic option for patients with acSCC. They recommend preferring first-line immunotherapy for patients with inoperable tumor.