Advanced squamous cell carcinoma: Treatment
Last updated: January 13, 2026
Dermatologist reviewed: Arturo Dominguez, MD, FAAD; Brittany Oliver, MD, FAAD. Reviewer bios.
What is advanced squamous cell skin cancer?
This skin cancer is diagnosed as advanced when the cancer does one of the following:
Grows deeper than the skin, reaching areas like muscle, bone, or nerves
Spreads to another part of the body, most commonly local lymph nodes
Has not responded to different treatments, such as surgery or radiation
Your dermatologist or oncologist may have told you what type of advanced squamous cell carcinoma you have. Here’s what each type means:
Locally advanced squamous cell carcinoma: This means cancer has grown deep and is found in nearby tissues, muscles, or nerves. This can happen when the tumor is large enough to reach beyond the skin.
Regional squamous cell carcinoma: This means cancer has spread to one or more lymph nodes closest to where squamous cell carcinoma first appeared on your skin.
Metastatic (distant) squamous cell carcinoma: This means the cancer has spread beyond the lymph nodes. When it does, the cancer is called “metastatic” or “distant” squamous cell carcinoma.
How is advanced squamous cell skin cancer treated?
Research breakthroughs have led the U.S. Food and Drug Administration (FDA) to approve medications for advanced squamous cell carcinoma. These treatments give patients hope. In clinical trials, a type of treatment called immunotherapy was found to kill cancer cells and shrink tumors for many patients. Immunotherapy works by boosting the patient’s immune system, so that it can attack cancer.
Even with breakthroughs, treatment for advanced squamous cell carcinoma is more complex. Patients often need more than one treatment. Many patients with this advanced cancer are cared for by a team of doctors who specialize in treating cancer. This team approach helps you get the care you need.
For any type of advanced squamous cell carcinoma, the treatment plan often includes one or more of the following:
Surgery: When surgery can remove the tumor and you’re healthy enough to have surgery, this is often the preferred treatment. After surgery, another treatment, such as radiation therapy, is often given. Adding another treatment helps to kill any remaining cancer cells.
Radiation therapy: Radiation can target cancer cells in the skin, lymph nodes, or other areas of the body. When a patient has advanced squamous cell skin cancer, radiation therapy is often used along with another treatment.
Immunotherapy: This type of treatment works with your body’s immune system to fight cancer. Immunotherapy helps some people with advanced cancer live longer.
The FDA has approved three immunotherapy medications to treat adults with advanced squamous cell skin cancer:
Cemiplimab-rwlc improves the immune system’s ability to recognize cancer cells, so the immune system can attack the cells more effectively.
In the clinical trials that led the FDA to approve cemiplimab-rwlc, about half the patients who had advanced squamous cell skin cancer had their tumors shrink. In many patients who had tumor shrinkage, the shrinkage lasted for 6 months or longer. A few patients had their tumors disappear completely.
Cemiplimab-rwlc is given by an intravenous (IV) infusion. The infusion for cemiplimab-rwlc usually takes about 30 minutes. Most patients go to a hospital or cancer treatment center once every 3 weeks to receive this infusion.
Patients continue to receive an infusion once every 3 weeks for either up to 24 or 48 months. How long treatment continues depends on the type of advanced squamous cell carcinoma you have.
Treatment stops earlier if the cancer returns or side effects become unmanageable.
Possible side effects include a rash on the skin, itching, hives, shortness of breath, and dizziness. More serious side effects can occur. These include damage to your liver or lungs. Report any side effects, including abdominal pain, diarrhea, fatigue, or fever to your doctor right away.
Brand name: Libtayo
Pembrolizumab helps your immune system better recognize cancer cells, so it can destroy them.
In clinical trials that led the FDA to approve this medication, patients saw their tumors shrink. Some had all signs of cancer disappear. At the end of the clinical trials, for patients with cancer in either their lymph nodes (regional) or cancer that had spread beyond their lymph nodes (distant), 68% maintained their results for one year or longer. For patients with cancer that had grown deeper than the skin so that it had reached an area like muscle or bone (locally advanced), 75% maintained their results for one year or longer.
If this medication is prescribed, you would receive an intravenous infusion every 3 or 6 weeks, depending upon your needs. Treatment may continue for up to 24 months.
If side effects become unmanageable or cancer progresses, treatment stops earlier.
The most common side effects include fatigue, pain in muscles or bones, some loss of appetite, itch, and diarrhea. More serious side effects can occur. These include damage to your liver or lungs. Report any side effects, including abdominal pain, diarrhea, fatigue, or fever to your doctor right away.
Brand name: Keytruda
Cosibelimab-ipdl can boost the immune system's ability to kill cancer cells.
In the clinical trials that led to FDA approval of this medication, many patients saw their tumors shrink, and a few had no signs of cancer. For most of these patients, the results lasted at least 6 months. For some patients, results lasted a year or longer.
If this medication is prescribed, you will receive infusions, which are given intravenously. For most patients, this infusion takes about 1 hour and is given every 3 weeks.
Patients continue receiving an infusion once every 3 weeks. Infusions are stopped if the cancer progresses or side effects become unmanageable. The most common possible side effects include feeling tired, pain in muscles or bones, rash, and diarrhea. More serious side effects can occur. These include damage to your liver or lungs. Report any side effects, including abdominal pain, diarrhea, fatigue, or fever, to your doctor right away.
Brand name: Unloxcyt
Like all medications, immunotherapy drugs are not right for every patient. Because immunotherapy medication changes the way your immune system works, some side effects from these medications can be serious.
Your doctor can tell you whether immunotherapy medication may be an option for you. If this is an option, you may receive only immunotherapy medication or be given this medication along with another cancer treatment.
Chemotherapy: This treatment can help slow spreading cancer and relieve symptoms. Sometimes, chemotherapy shrinks tumors.
There are many different chemotherapy drugs. The ones used to treat advanced squamous cell skin cancer are usually given intravenously.
Chemotherapy drugs work by killing fast-growing cells in the body. Cancer cells are just one type of cell that grows quickly. Hair cells and cells in your gastrointestinal (GI) tract (includes your mouth, stomach, and intestines) also grow quickly and can be killed. When chemotherapy kills these cells, patients develop side effects, such as hair loss and nausea.
Clinical trial: This is a research study that doctors and other scientists use to:
Find out how well a medication works to treat patients with a specific disease, such as a type of cancer.
Test new ways to find and prevent a disease like cancer.
Learn better ways to manage side effects of medications.
Before the FDA approved the medications used to treat advanced squamous cell carcinoma, each of these medications was tested in clinical trials.
Observation: Instead of treating the cancer, your dermatologist watches you. You’ll see your dermatologist as recommended, so they can continue to examine you. Patients continue to return as often as recommended until they can either have treatment or must treat the cancer due to symptoms like pain or bleeding.
Palliative care: This type of care focuses on helping patients feel more comfortable. It can also address side effects that can occur during treatment and improve a patient’s overall well-being. Palliative care is available to all patients who have cancer. It’s neither hospice care nor end-of-life care. Palliative care specialists develop expertise in helping patients feel more comfortable. They also provide support to caregivers.
Other treatments for advanced squamous cell skin cancer: No single treatment is best for everyone who has this advanced cancer. Your medical care team will consider your unique needs. Another type of treatment may be recommended.
Talk with your care team
It’s important to talk with your care team about treatment. Many considerations play a role in choosing treatment for advanced squamous cell carcinoma. One essential consideration is your wishes. Speaking with members of your care team also gives you an opportunity to ask questions. For example, you may want to know when each treatment will be done and how long treatment will take. You may want to know about side effects and what to watch for. Some patients want to know how they will look after treatment and in the long term.
Asking questions and discussing treatment can help you know what to expect. It can help your care team determine the most appropriate treatment based on cure rate, your age, medical conditions, and desires.
Related AAD resources
Squamous cell carcinoma: From symptoms to treatment: Discover where this skin cancer can appear, how it’s diagnosed and treated, and who’s likely to develop it.
Pictures of squamous cell carcinoma: See different ways this skin cancer can appear on the skin.
Squamous cell carcinoma: Outcome and life after treatment: Find out why most patients have a good outcome and what dermatologists tell their patients after treatment.
Dermatologist reviewer bios
Arturo R. Dominguez, MD, FAAD
Dr. Dominguez is an Associate Professor of Dermatology and Internal Medicine at UT Southwestern Medical Center. Board-certified in both dermatology and internal medicine, he also serves as an attending physician on the internal medicine residency teaching service at Parkland Health & Hospital System in Dallas.
Born and raised in towns along the United States – Mexico border, Dr. Dominguez is dedicated to improving access to medical care in Latino communities. He volunteers monthly at the Agape Clinic in Dallas and performs free skin cancer checks at Latino health fairs.
At the William P. Clements Jr. University Hospital, which has a specialized clinic for transplant patients, he screens patients for skin cancer who are candidates for an organ transplant.
Dr. Dominguez is also involved in clinical trials. These trials focus on severe drug reactions and autoimmune blistering disorders. His research has been published in leading journals including the Journal of the American Academy of Dermatology, JAMA Dermatology, and The British Journal of Dermatology.
Brittany Oliver, MD, FAAD
Dr. Oliver is a board-certified dermatologist and Assistant Professor of Dermatology at the University of Missouri – Kansas City. She has extensive experience treating skin cancer and helping high-risk patients reduce their risk of developing skin cancer. This passion extends to helping everyone reduce their risk and find skin cancer early when it’s highly treatable. To this end, you’ll find her on social media, using science-backed facts to raise awareness. Her posts include tips to help people with darker skin tones find skin cancer earlier. Too often, people who have darker skin tones are diagnosed with skin cancer that has grown large or deep.
Dr. Oliver is regularly featured in online publications, including WebMD, Vogue, and The Wall Street Journal. Castle Connolly, known for its peer-reviewed lists of "Top Doctors," recognizes her as a Rising Star in dermatology.
Written by Paula Ludmann, MS
Paula has more than 20 years of experience writing about skin, hair, and nail conditions for patients and the public.
She enjoys developing easy-to-understand information that people can use to make informed health decisions.
Paula’s passion for creating patient-first information has led to her work being mentioned by Prevention magazine and the Washington Post. She has won numerous awards, including Webbies, Apex Awards, and several awards from professional organizations.
References
Migden MR, Rischin D, et al. “PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma.” N Engl J Med. 2018 Jul 26;379(4):341-51.
Que SKT, Zwald FO, et al. “Cutaneous squamous cell carcinoma: Management of advanced and high-stage tumors.” J Am Acad Dermatol. 2018 Feb;78(2):249-61.
Ribero S, Stucci LS, et al. “Drug therapy of advanced cutaneous squamous cell carcinoma: Is there any evidence?” Curr Opin Oncol. 2017;29(2):129-35.
U.S. Food and Drug Administration:
“FDA approves cemiplimab-rwlc for metastatic or locally advanced cutaneous squamous cell carcinoma.” Issued: September 28, 2018. Last accessed: October 9, 2025.
Cemiplimab-rwlc package insert (revised October 2025). Last accessed: October 27, 2025.
Cosibelimab-ipdl package insert (revised December 2024). Last accessed: October 27, 2025.
Pembrolizumab package insert (revised July 2025). Last accessed: October 27, 2025.
Vaidya P, Mehta A, et al. “Concurrent radiation therapy with programmed cell death protein 1 inhibition leads to a complete response in advanced cutaneous squamous cell carcinoma.” JAAD Case Rep. 2019; 5(9): 763–6.