S17 Ep56: Navigating Systemic Therapy Selection and Sequencing in Advanced CSCC: With Neil D. Gross, MD, FACS

In today’s episode, we spoke with Neil D. Gross, MD, FACS. Dr Gross is the medical director of Perioperative Surgical Services, section chief of Oropharynx Cancer, Surgery, and professor of head and neck surgery at The University of Texas MD Anderson Cancer Center in Houston. In our exclusive interview, Dr Gross discussed the key biological and clinical distinctions between cutaneous squamous cell carcinoma (CSCC) and basal cell carcinoma (BCC), noting that although BCC is more indolent and less responsive to systemic therapies, including immunotherapy, CSCC carries a meaningful risk of nodal and distant metastases and has demonstrated robust responses to anti–PD-1 therapy, with approximately half of patients achieving a significant response.He emphasized the importance of early multidisciplinary evaluation, with resectability serving as a critical first branch point in treatment planning. For patients with unresectable or metastatic CSCC, anti–PD-1 therapy is now the established standard of care. For borderline resectable patients, such as those at risk for significant functional loss from surgery, upfront systemic therapy offers the potential to preserve function and achieve cure. For resectable, high-risk patients, Gross highlighted the role of adjuvant cemiplimab-rwlc (Libtayo) following surgery and radiation, based on data from the phase 3 C-POST trial (NCT03969004).The discussion also addressed toxicity considerations in elderly and immunocompromised patients, populations Gross described as particularly high risk and underserved. He noted that although anti–PD-1 therapies are generally well tolerated, serious toxicities remain possible, underscoring the importance of careful patient monitoring in both adjuvant and investigational neoadjuvant settings.Finally, Gross highlighted the actively accruing phase 3 NRG-HN014 trial (NCT06568172), a National Cancer Institute–sponsored cooperative group study open across the United States, Canada, and Australia, which is evaluating a neoadjuvant approach vs upfront surgery in patients with advanced resectable CSCC. He also noted that more mature data from C-POST, as well as long-term phase 2 neoadjuvant findings, are anticipated later this year.