Neoadjuvant Immunotherapy Expands Options in Complex CSCC

Neoadjuvant immunotherapy is emerging as one of the most promising advances in the management of cutaneous squamous cell carcinoma (CSCC), particularly for patients with large, complex, or borderline resectable tumors. According to Vishal Anil Patel, MD, of the George Washington Cancer Center, this approach is especially valuable when surgery alone may lead to significant morbidity, functional impairment, or difficulty achieving clear margins.

PD-1 inhibitors such as cemiplimab can be administered before surgery to stimulate a robust immune response while the tumor is still present, enhancing immune recognition and potentially leading to durable disease control. In many cases, neoadjuvant therapy can shrink tumors, allowing for less extensive and less disfiguring surgical procedures while maintaining oncologic effectiveness. Additionally, the surgical specimen itself serves as a biomarker of treatment response; patients who achieve a complete pathologic response have shown very low rates of recurrence in emerging data.

This strategy is particularly relevant for tumors involving critical structures—such as the face, orbit, or major nerves—or those with rapid growth and aggressive features. In borderline resectable disease, systemic therapy expands treatment options by improving resectability and preserving both function and appearance.

Despite its promise, neoadjuvant immunotherapy remains an evolving approach, supported primarily by phase 2 and smaller studies involving agents like pembrolizumab and nivolumab. While widely used in practice, it is not yet FDA approved in this setting, and phase 3 data are still needed to establish a standard of care.

Patient selection remains central to decision-making. Clinicians must weigh tumor characteristics alongside patient-specific factors such as comorbidities, performance status, and the ability to tolerate immune-related adverse events. Although PD-1 inhibitors are generally well tolerated—even in older adults—careful monitoring is essential, particularly in immunocompromised populations.

Overall, Patel emphasizes that neoadjuvant immunotherapy is expanding the role of systemic therapy earlier in the disease course, improving surgical outcomes and potentially long-term disease control.