Selecting Patients for Immunotherapy in CSCC: Key Considerations

The management of cutaneous squamous cell carcinoma (CSCC) is undergoing a notable shift, with systemic immunotherapy playing an increasingly important role alongside surgery. According to Vishal Anil Patel, MD, of the George Washington Cancer Center, clinicians should begin considering systemic therapy earlier in the disease course—particularly for patients beyond the lowest-risk category.

While low-risk CSCC remains highly treatable with surgery alone, Patel emphasizes that the disease is fundamentally immunologically driven and highly responsive to checkpoint inhibitors. As a result, clinicians should assess whether immunotherapy may be appropriate not only for unresectable or metastatic disease—where it is already standard—but also for patients with larger, moderate-risk tumors that are technically resectable but may benefit from additional therapeutic strategies.

Current National Comprehensive Cancer Network guidelines reflect this evolution, encouraging multidisciplinary evaluation and earlier consideration of systemic therapy. Patel notes that even in resectable cases, collaboration among dermatologists, surgeons, medical oncologists, and radiation oncologists can help determine whether neoadjuvant or adjuvant immunotherapy could improve outcomes. Emerging research is also exploring intralesional immunotherapy in earlier-stage disease, signaling a potential future expansion of treatment options.

Decisions around systemic therapy rely on both tumor-specific and patient-specific factors. Tumor characteristics such as size, resectability, metastatic status, and the presence of very-high-risk features often guide treatment escalation. Equally important are patient considerations, including overall health, comorbidities, performance status, and the ability to tolerate therapy.

Special populations, such as organ transplant recipients, present additional challenges, as standard immunotherapies—particularly PD-1 inhibitors—can increase the risk of graft rejection. However, newer agents like cosibelimab may offer safer alternatives, though further data are needed.

Ultimately, Patel underscores that treatment decisions should be individualized and guided by shared decision-making, balancing potential benefits with risks to optimize patient outcomes.