Skin Cancer Radiotherapy
High-Risk Cutaneous Squamous Cell Cancer: C-POST Explained
The phase 3 C-POST trial found adjuvant cemiplimab improved disease-free survival after surgery and postoperative radiation for selected high-risk cSCC.
Short answer: C-POST found that cemiplimab reduced recurrence after surgery and postoperative radiation in selected people with high-risk cutaneous squamous cell carcinoma. This is an immunotherapy result for advanced-risk care—not evidence that every skin cancer needs medication or postoperative radiation.
Who entered the trial?
C-POST randomized 415 participants whose high-risk cSCC had been removed surgically and treated with postoperative radiation. Risk features included nodal disease with extracapsular extension or multiple involved nodes, certain T4 tumors, perineural invasion, or locally recurrent tumors with additional adverse features.
That population is very different from most small BCCs, SCC in situ lesions, or low-risk invasive SCCs treated in a dermatology office.
What did cemiplimab change?
At a median follow-up of 24 months:
- estimated two-year disease-free survival was 87.1% with cemiplimab;
- it was 64.1% with placebo; and
- the hazard ratio for recurrence or death was 0.32.
Locoregional and distant recurrences were also less frequent in the cemiplimab group.
What were the harms?
Grade 3 or higher adverse events occurred in 23.9% with cemiplimab and 14.2% with placebo. Treatment discontinuation because of adverse events occurred in 9.8% and 1.5%, respectively.
Checkpoint inhibitors can cause the immune system to inflame healthy organs, including thyroid, bowel, lung, liver, skin, and endocrine glands. Some effects can be serious or long lasting.
Where does radiation fit?
Everyone in the trial had already received postoperative radiation. C-POST therefore tested whether systemic therapy added benefit after local surgery and radiation; it did not test cemiplimab instead of radiation.
Postoperative radiation itself is reserved for appropriate risk features. A multidisciplinary team should review pathology, nodal disease, margin status, perineural invasion, immune status, and prior treatment.
What should patients ask?
Ask which feature makes the cancer high risk, whether the case matches C-POST eligibility, what recurrence reduction is expected, and how immune-related side effects will be monitored. The trial is an important advance, but its numbers should never be used to promote routine superficial radiation for low-risk lesions.
Questions patients often ask
What is cemiplimab?
It is a PD-1 immune checkpoint inhibitor. It is systemic drug therapy, not radiation.
Who was represented in C-POST?
Participants had high-risk cutaneous squamous cell carcinoma and had already completed surgery plus postoperative radiation.
Does C-POST change treatment for a small early skin cancer?
Usually not. The trial addressed selected high-risk disease, not routine superficial BCC, SCC in situ, or small low-risk invasive SCC.
Sources and further reading
- Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma. The New England Journal of Medicine (2025).
- ASTRO Guideline on Definitive and Postoperative Radiation Therapy for Basal and Squamous Cell Cancers. American Society for Radiation Oncology (2020).
