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It’s an exciting time for dermatologists and oncologists who care for patients with cutaneous squamous cell carcinoma (cSCC) and a time of hope for patients with locally advanced and metastatic cSCC, according to Vishal Anil Patel, MD. He is the Director of Cutaneous Oncology at GW Cancer Center, the Director of Dermatologic Surgery at the GW Department of Dermatology, and an Associate Professor of Dermatology & Hematology/Oncology at George Washington University School of Medicine & Health Sciences in Washington, DC.

Dr. Patel chatted with Practical Dermatology® about the role that immunotherapy is playing in treating these cancers—as well as other new approaches on the horizon.

What’s new in cSCC?

Vishal Anil Patel, MD: There is a lot new in cSCC. Recently, we have seen the development of a gene expression profiling test that can accurately predict the risk for nodal and distant metastasis in patients with high-risk cSCC, the publication of a landmark study in the New England Journal of Medicine of neoadjuvant cemiplimab in advanced resectable cSCC that showed that a nearly 70% major pathologic response after only four doses, and the start of clinical trials of intralesional cemiplimab for low-risk cSCC.1

What targeted/immunotherapy drugs seem to be most effective in cSCC?

Dr. Patel: Cemiplimab and pembrolizumab are both approved for locally advanced and metastatic cSCC in patients who are not candidates for definitive surgery or radiation. Both appear to be fairly equal in their effectiveness to treat non-operable advanced and metastatic tumors with response rates of nearly 50%. Furthermore, cemiplimab was recently shown to have a nearly 70% major pathologic response when given for four doses prior to surgery of high-risk advanced cSCC tumors. Of patients in this trial, about 50% had a complete response and another approximately 20% had a major response with less than 10% viable tumor cells seen in the tumor resection.1

What is high-risk cSCC?

Dr. Patel: High-risk cSCC is generally considered tumors that are American Joint Committee on Cancer (AJCC) Stage T3 or above or Brigham and Women’s stage T2b and above. These tumors tend to be >2 cm, deeply invade into and beyond the fat, or have large-caliber nerve perineural invasion. There are other risk factors that can denote high-risk behavior, and the National Comprehensive Cancer Network (NCCN) has created a “very high risk” category to help identify very worrisome risk factors and help separate these risk factors from other high-risk but less risky factors. Some very high-risk features include desmoplasia, poor differentiation, and lymphovascular invasion.

What are you most excited about for the future of cSCC and basal cell carcinoma (BCC)?

Dr. Patel: Immunotherapy is a game-changer for nonmelanoma skin cancer, and we are just scratching the surface. In the future, we will likely have the ability to use intralesional therapy on low-risk tumors that are not able to be surgically resected or even potentially use immunotherapy in organ transplant patients to safely treat high-risk tumors in this vulnerable population. We also are seeing the development of other adjuvant immunotherapies—both systemic and intralesional, such as oncolytic virus and Toll-like receptor agonists, to enhance the current efficacy of programmed cell death protein 1 inhibitors. Furthermore, we are learning more about the potential for topical immunotherapy, which will further enhance our ability to treat and prevent nonmelanoma skin cancers from becoming an advanced problem.

Why should nonmelanoma skin cancers be taken more seriously by the public?

Dr. Patel: We now know that BCC and cSCC can have serious sequela and complications. Furthermore, cSCC deaths are estimated to actually be higher than melanoma deaths each year. Thus, these cancers should be taken seriously to prevent progression or to treat high-risk tumors appropriately from the get-go. BCC, if neglected, can cause severe morbidity for a patient, while cSCC mortality rises exponentially if tumors progress to the regionally metastatic stage. While the vast majority of these tumors are treated successfully, one should not confuse this with being a good cancer for which you can postpone treatment.

1. Gross ND, Miller DM, Khushalani NI, et al. Cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. N Engl J Med. 2022;387:1557-1568. doi:10.1056/NEJMoa2209813.

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