Advanced Cutaneous Squamous Cell Carcinoma: Treatment Options and What’s New
Authored by
Emily Karn
What is advanced cutaneous squamous cell carcinoma?
Cutaneous squamous cell carcinoma (cSCC) is considered advanced when the cancer cannot be completely removed with surgery, cannot be cured with radiation, or has spread beyond the original tumor. (1) At this stage, treatment may shift from local therapies, such as surgery or radiation, to medicines that work throughout the body (systemic therapy).(1,2)
Advanced disease may be locally advanced, meaning the tumor has grown into nearby tissues such as muscle, bone, or nerves, or metastatic, meaning the cancer has spread to other parts of the body, including lymph nodes or distant organs.(1)
How treatment has evolved
Treatment for advanced cutaneous squamous cell carcinoma has evolved over time as researchers have developed new approaches to care. When surgery or radiation are not possible, newer therapies may help provide longer control of disease and support quality of life.(2) One of these approaches is immunotherapy, which helps the body’s immune system recognize and attack cancer cells.
How these treatments work
Cutaneous squamous cell carcinoma develops when changes in skin cells cause them to grow abnormally. Because cancer cells differ from normal cells, the immune system may be able to recognize them as harmful.(2) However, cancer cells can sometimes hide from the immune system by sending a “stop signal” that prevents immune cells from attacking.(2,3)
Immune checkpoint inhibitors work by blocking this signal allowing the immune system to remain active against cancer. This helps the body’s natural defenses recognize and fight the tumor more effectively.(2,3)
Available treatment options today
Over the past several years, immunotherapy has changed how advanced cutaneous squamous cell carcinoma is treated. In 2018, the first immune checkpoint inhibitor for advanced cSCC, cemiplimab, was approved in the United States.(4) This was followed by approval of another similar therapy, pembrolizumab, in 2020.(5) These treatments help keep the immune system active against cancer and have shown meaningful benefit for some patients.(2,4,5)
In 2024, cosibelimab (Unloxcyt) was approved as an additional treatment option for adults with advanced cSCC that cannot be cured with surgery or radiation.(6) Like earlier immunotherapies, it works by helping the immune system respond to cancer. The availability of additional treatment options allows patients and clinicians more flexibility when choosing care.
In recent years, there has been important progress in the treatment of advanced cutaneous squamous cell carcinoma. New therapies that help the immune system fight cancer are giving patients and caregivers more options than before. Research continues to bring new understanding and new treatment possibilities for those with advanced cSCC.
References
Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 2018;78(2):237-247.
Boutros A, Cecchi F, Tanda ET, et al. Immunotherapy for the treatment of cutaneous squamous cell carcinoma. Front Oncol. 2021;11:733917.
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264.
Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. Lancet Oncol. 2020;21(2):294-305.
Grob JJ, Gonzalez R, Basset-Seguin N, et al. Pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma. J Clin Oncol. 2020;38(25):2916-2925.
Ruiz ES, et al. Efficacy and safety of cosibelimab in advanced cutaneous squamous cell carcinoma: results from a multicenter clinical study. J Am Acad Dermatol. 2026.