How I Treat: Cutaneous Squamous Cell Carcinoma Case Presentation

Advances in prognostics and systemic therapy are reshaping how dermatologists assess and manage high-risk cutaneous squamous cell carcinoma (cSCC), according to an in-depth interview with Vishal Patel, MD. He outlined how gene expression profiling (GEP) and neoadjuvant immunotherapy are beginning to complement traditional staging systems, offering more personalized approaches for a disease long managed with limited tools.

Dr Patel emphasized that GEP is still early in its integration into routine cSCC care but represents a clear shift toward precision oncology. “Genetic expression profiling and personalized risk stratification is becoming more commonplace across all cancers…and high-risk cutaneous squamous cell carcinoma is not any different,” he said. While conventional staging systems such as the Brigham and Women’s Hospital and American Joint Committee on Cancer frameworks remain effective for most tumors, they leave gaps, particularly for lesions that fall into intermediate-risk categories.

In these gray-zone cases, GEP can provide an additional data point. Dr Patel described using GEP selectively when results may meaningfully influence decisions, such as surveillance intensity or whether to add adjuvant radiation. “I ask myself first, is this test going to change my treatment decision?” he said, noting that GEP can be helpful when clinicians are weighing less aggressive management in frail patients or those with limited access to follow-up care.

At the same time, he cautioned against overreliance on GEP in the absence of prospective trials linking test results to improved outcomes. “We’re only beginning to understand how to incorporate that into the decision-making process,” he said. For most low-risk cSCCs, and even many clearly high-risk tumors, management decisions are already evident based on clinical and histologic features alone.

Dr Patel is enthusiastic about treatment innovation, specifically neoadjuvant immunotherapy. Recent data using cemiplimab prior to surgery in high-risk or borderline resectable cSCC have been practice changing. “Greater than 50% of tumors had complete responses and almost two-thirds of patients were major pathologic responders,” Dr Patel noted. Event-free and metastasis-free survival exceeded 90% in responders, outcomes he described as “unheard of numbers” for this aggressive disease subset.

This approach is altering how clinicians think about sequencing therapy. Rather than defaulting to extensive surgery followed by radiation, neoadjuvant immunotherapy may downstage tumors, reduce surgical morbidity, and potentially spare patients from adjuvant radiation. “We’re considering whether they are candidates for this neoadjuvant immunotherapy approach of systemic therapy first and then surgery,” Dr Patel said.

These therapeutic advances also influence the role of risk prediction. In patients presenting with clearly advanced disease, the priority shifts from forecasting recurrence to achieving the deepest initial response. “We’re trying to get that deepest response from the first surgical get-go,” he explained.

For dermatologists, the key takeaway is that high-risk cSCC management is moving toward a more dynamic, individualized model. GEP may help refine decisions in select cases, while neoadjuvant immunotherapy is emerging as a powerful option for advanced tumors. Dr Patel stressed the importance of multidisciplinary care and ongoing education, noting that cSCC increasingly overlaps with principles long applied in melanoma and other cutaneous malignancies. As evidence continues to evolve, dermatologists will need to balance emerging tools with clinical judgment to deliver risk-adapted, patient-centered care.

Watch Dr Patel’s full interview here.