The first 60 days: Advanced cutaneous squamous cell carcinoma
Advanced cutaneous squamous cell carcinoma is a skin cancer that has grown beyond what surgery or radiotherapy can remove or has spread to lymph nodes or organs. Because sun damage gives it more mutations than almost any other cancer, immunotherapy works well: cemiplimab or pembrolizumab shrinks about half of tumours, often for years, and cemiplimab before surgery can make large tumours vanish. Below, week by week, is what OnCo's record of Advanced cutaneous squamous cell carcinoma says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- SurgeonNamed in the standard of care for: High-risk resectable disease, Transplant recipients.
- Medical oncologistNamed in the standard of care for: High-risk resectable disease, Adjuvant after surgery and radiotherapy, Locally advanced or metastatic, first line, Immunotherapy-ineligible or refractory and 1 more.
- Clinical oncologist (radiotherapy)Named in the standard of care for: High-risk resectable disease, Locally advanced or metastatic, first line, Immunotherapy-ineligible or refractory, Transplant recipients.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Cemiplimab for high-risk disease (C-POST, 2025).
Excision with margin control or Mohs surgery, nodal evaluation, and postoperative radiotherapy for perineural invasion, positive margins or nodal disease; neoadjuvant cemiplimab to shrink large tumours before surgery.
Cemiplimab (EMPOWER-CSCC-1), pembrolizumab (KEYNOTE-629) or cosibelimab; radiotherapy for symptomatic sites.
Reduce immunosuppression and switch to sirolimus or everolimus where possible; PD-1 blockade only after weighing graft rejection risk; surgery and radiotherapy preferred.
Cetuximab with or without radiotherapy, platinum-based chemotherapy, capecitabine; clinical trials of RP1 with cemiplimab or photoimmunotherapy.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Tumour mutational burden, Perineural and lymphovascular invasion, Depth of invasion and differentiation grade, Immunosuppression status, PD-L1 expression), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Locally advanced cutaneous squamous cell carcinoma, Nodal metastatic cutaneous squamous cell carcinoma, Distant metastatic cutaneous squamous cell carcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
High-risk resectable disease
- For my situation (high-risk resectable disease), which of the standard options do you recommend and why?Guideline options include: Excision with margin control or Mohs surgery, nodal evaluation, and postoperative radiotherapy for perineural invasion, positive margins or nodal disease; neoadjuvant cemiplimab to shrink large tumours before surgery.
- Am I a candidate for Cemiplimab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Adjuvant after surgery and radiotherapy
- For my situation (adjuvant after surgery and radiotherapy), which of the standard options do you recommend and why?Guideline options include: Cemiplimab for high-risk disease (C-POST, 2025).
- Am I a candidate for Cemiplimab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Locally advanced or metastatic, first line
- For my situation (locally advanced or metastatic, first line), which of the standard options do you recommend and why?Guideline options include: Cemiplimab (EMPOWER-CSCC-1), pembrolizumab (KEYNOTE-629) or cosibelimab; radiotherapy for symptomatic sites.
- Am I a candidate for Cemiplimab, Pembrolizumab, Cosibelimab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of EMPOWER-CSCC-1 and KEYNOTE-629 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Immunotherapy-ineligible or refractory
- For my situation (immunotherapy-ineligible or refractory), which of the standard options do you recommend and why?Guideline options include: Cetuximab with or without radiotherapy, platinum-based chemotherapy, capecitabine; clinical trials of RP1 with cemiplimab or photoimmunotherapy.
- Am I a candidate for Cetuximab, Carboplatin, Vusolimogene oderparepvec, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer and An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Transplant recipients
- For my situation (transplant recipients), which of the standard options do you recommend and why?Guideline options include: Reduce immunosuppression and switch to sirolimus or everolimus where possible; PD-1 blockade only after weighing graft rejection risk; surgery and radiotherapy preferred.
- Am I a candidate for Everolimus, Cemiplimab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer, An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors, Study of Intralesional Cemiplimab in Adult Patients With Early Stage Cutaneous Squamous Cell Carcinoma, HMBD-001?Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
- I read that “Transplant recipients, who have the highest incidence, cannot safely receive the most effective drugs”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “About half of patients do not respond to PD-1 blockade and there is no approved second-line therapy”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- Study of Intralesional Cemiplimab in Adult Patients With Early Stage Cutaneous Squamous Cell CarcinomaPhase 3 · recruiting · NCT06585410A Phase 3 Randomized Study of Intralesional Cemiplimab Versus Primary Surgery in Participants With Early Stage Cutaneous Squamous Cell Carcinoma (CSCC)
- Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin CancerPhase 2 · active · NCT04050436A Randomized, Controlled, Open-Label, Phase 2 Study of Cemiplimab as a Single Agent and in Combination With RP1 in Patients With Advanced Cutaneous Squamous Cell Carcinoma
- An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid TumorsPhase 1/2 · active · NCT04305795An Open-label Study Using ASP-1929 Photoimmunotherapy in Combination With Anti-PD1 Therapy in EGFR Expressing Advanced Solid Tumors
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Advanced cutaneous squamous cell carcinoma: the full pageAdvanced cutaneous squamous cell carcinoma is a skin cancer that has grown beyond what surgery or radiotherapy can remove or has spread to lymph nodes or organs. Because sun damage gives it more mutations than almost any other cancer, immunotherapy works well: cemiplimab or pembrolizumab shrinks about half of tumours, often for years, and cemiplimab before surgery can make large tumours vanish.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Mohs surgery: Skin cancer surgery in which the tumour is removed in thin layers, each checked under the microscope on the spot, until the edges are clear; it spares the most normal skin.
- Tumour mutational burden (TMB): How many mutations a tumour has.
- Pathologic complete response (pCR): No invasive cancer left in the breast and lymph nodes when the surgeon removes the tissue after pre-surgery treatment.
- Neoadjuvant / adjuvant / perioperative: Neoadjuvant therapy is treatment given before surgery, adjuvant therapy is treatment given after it, and perioperative therapy is both.
Every term links to the glossary.