The treatment algorithm for cutaneous squamous cell carcinoma (CSCC) has shifted markedly over the past year, from a positive phase 3 adjuvant trial to an expanding neoadjuvant paradigm that is changing when and how surgery is used, according to faculty who participated in a recent OncLive® Scientific Interchange and Workshop held during the 2026 American Society of Clinical Oncology Annual Meeting (ASCO 2026).1
"I think it's pretty impressive how this field has changed," Adil I. Daud, MBBS, codirector of the Melanoma Center and director of melanoma clinical research at UCSF Medical Center in San Francisco, California, said during the workshop. “[In terms of our] surgical colleagues and dermatologists, I feel there's been a major change in their impression. Over the past couple of years, I think it’s the most I've treated anybody. It's been pretty impressive.”
Moderated by Soo Park, MD, an associate professor in the Division of Hematology-Oncology and a hematologist and medical oncologist in the Cutaneous Oncology Program at the UC San Diego Moores Cancer Center, the multidisciplinary panel worked through the current guideline landscape, high-risk definitions, and emerging biomarker data across the adjuvant, neoadjuvant, and advanced-disease settings.
Top Takeaways From an OncLive Workshop on Evolving Decision-Making in CSCC
- Neoadjuvant immunotherapy is reshaping surgical decision-making, allowing surgery to be deferred, de-escalated, or, in some cases, omitted in patients who achieve a pathologic or clinical complete response.
- Adjuvant cemiplimab cut the risk of recurrence or death by 68% vs placebo in high-risk resected CSCC in C-POST (HR, 0.32; 95% CI, 0.20-0.51; P < .001), whereas adjuvant pembrolizumab missed its primary end point of RFS in KEYNOTE-630, and the trial was stopped for futility.
- Cosibelimab produced ORRs of 50% in metastatic and 54.8% in locally advanced CSCC with a favorable toxicity profile, offering a PD-L1–directed option alongside PD-1 inhibitors.
Do the C-POST trial results support adjuvant cemiplimab as a new standard in high-risk CSCC?
The participants first acknowledged that no single, universally accepted staging or high-risk definition exists for CSCC. NCCN, European Association of Dermato-Oncology, American Joint Committee on Cancer, and Brigham and Women's Hospital criteria each capture different features, and none accounts for nodal or distant disease.
Against that backdrop, the phase 3 C-POST trial (NCT03969004) randomly assigned 415 patients with high-risk resected CSCC to adjuvant cemiplimab-rwlc (Libtayo; n = 209) or placebo (n = 206). Data from C-POST demonstrated that cemiplimab reduced the risk of recurrence or death by 68% vs placebo (HR, 0.32; 95% CI, 0.20-0.51; P < .001).2
In contrast, in the phase 3 KEYNOTE-630 trial (NCT03833167), adjuvant pembrolizumab (Keytruda) produced a relapse-free survival HR of 0.76 compared with placebo (95% CI, 0.53-1.10; P = .07) and was stopped for futility, a result faculty attributed to trial design and a lower-risk population rather than inferior drug activity.3
“This is a population that is lost in being able to see us because a lot of these patients are actually seen by dermatology and then sometimes just get recurring Mohs [surgery]. Most surgeons and dermatologists don't necessarily know these data, and then [patients] see us a little too late,” Park noted.
How is neoadjuvant immunotherapy changing the role of surgery in CSCC?
John Haanen, MD, PhD, the head of the Division of Medical Oncology at the Netherlands Cancer Institute/Antoni van Leeuwenhoek in Amsterdam, summarized the field's direction by noting that investigators are moving away from surgery and radiotherapy and toward curative treatment.
