Treatment Update: Basal Cell and Squamous Cell Cancer

At the time of diagnosis, most cases of BCC and SCC have not spread from their original locations and are managed with local treatments, including the use of topical medications (applied directly to the skin) such as fluorouracil (Efudex) or surgical removal of the tumor.

If the tumor is removed surgically, the tissue is sent to a pathologist who checks to make sure the entire tumor was removed. In some cases, a second operation may be needed to remove more of the tumor.

Imiquimod cream can be applied to the biopsy site of certain BCCs to treat any cancer cells that remain. This treatment is typically given 5 days a week for 6 weeks. The most common side effect is irritation at the site of application.

There are certain superficial types of BCC and SCC that can be treated by performing small in-office procedures, including electrodessication and curettage (sometimes called “scrape and burn”) for BCC and two cycles of cryotherapy (freezing) for SCC.

Mohs micrographic surgery, a precise surgical technique, is often used to treat BCC and SCC that appears on the head and neck. This is a skin-sparing technique, in which pieces of skin are progressively removed at the site of the tumor and examined under a microscope until only cancer-free tissue remains.

If surgery is not an option, radiation may be considered. Radiation may also be used after surgery if there is concern about the risk of the skin cancer recurring (coming back).

Even though these types of skin cancers are very common, relatively few evolve into cases that require more intensive treatment. In advanced cases of BCC and SCC, surgery or radiation may not be an option. In these situations, immunotherapies or targeted therapies are often prescribed.

Immunotherapies are treatments that take advantage of the body’s immune system to fight cancer. These treatments are often administered intravenously (into a vein). Targeted therapy focuses on specific molecules and cell mechanisms thought to be important for cancer cell survival and growth, taking advantage of what researchers have learned in recent years about how cancer cells grow. Some targeted therapies are given in pill form; others are given intravenously.

Advanced Basal Cell Skin Cancer

More than 90 percent of BCCs have certain gene mutations (changes) in what is called the Hedgehog pathway. These changes activate the growth of cancer cells and allow for their survival. Drugs have been designed to target mutations in the Hedgehog pathway.

The Hedgehog inhibitors approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced BCC are vismodegib (Erivedge) and sonidegib (Odomzo). Taken orally, these drugs are used in cases where the BCC has spread to other parts of the body, has recurred after surgery or cannot be treated with surgery or radiation. Hedgehog inhibitors are sometimes used before surgery to shrink the size of a tumor, making surgery an easier process and increasing its chance of success.

In February 2021, the FDA approved cemiplimab-rwlc (Libtayo) for the treatment of locally advanced or metastatic BCC that was previously treated with a Hedgehog inhibitor or for which a Hedgehog inhibitor is not appropriate.

Advanced Squamous Cell Skin Cancer

There are two immunotherapies used in the treatment of advanced SCC, both of which are given via intravenous infusion:

• In 2018, the FDA approved the immunotherapy cemiplimab-rwlc (Libtayo) for the treatment of people with metastatic or locally advanced SCC who are not candidates for surgery or radiation.

• In June 2020, the FDA approved the immunotherapy drug pembrolizumab (Keytruda) for the treatment of recurrent or metastatic SCC that is not curable by surgery or radiation. In July 2021, the approval was expanded to include treatment of locally advanced SCC that is not curable by surgery or radiation.

The targeted therapy cetuximab (Erbitux) is sometimes prescribed to treat people whose SCC tumors cannot be surgically removed or treated with radiation. By attaching to a structure on the cell called the epidermal growth factor receptor (EGFR), cetuximab can block one of the signals that tells a tumor to grow.

All cancer treatments can cause side effects. It’s important that you report any side effects you experience to your health care team so they can help you manage them. Report them right away—don’t wait for your next appointment. It’s important to remember that not all people experience all side effects, and some people may experience side effects not listed here.

Side Effects of Radiation Therapy

Changes to the skin are the most common side effects of radiation therapy. The changes can include dryness, swelling, peeling, redness and blistering. If a reaction occurs, contact your health care team so the appropriate treatment can be prescribed. It’s especially important to contact your health care team if there is any open skin or painful area, as this could indicate an infection. Infections can be treated with an oral antibiotic or topical antibiotic cream. Other common side effects of radiation therapy include fatigue, hair loss and changes in skin color at the radiation site, or damage to salivary glands or teeth when treating cancers near these areas.

Side Effects of Immunotherapy

Immunotherapy helps to prompt an immune response throughout the body. Sometimes the immune system can attack healthy cells as well as cancer cells, and certain side effects may be experienced. The most common side effects are fatigue, decreased appetite and skin rash. Lightening of the skin (vitiligo) can also occur, and may be permanent. More rare and serious side effects of immunotherapy include inflammation in the lung (pneumonitis) which can cause difficulty breathing, or frequent diarrhea (colitis). Immunotherapy can also affect the thyroid gland, so thyroid levels are typically monitored while on treatment.

Side Effects of Targeted Therapy

The potential side effects of targeted therapy depend on the type of drug given, and can include taste alteration, hair thinning, muscle cramps or joint pain, sun sensitivity, liver problems (such as hepatitis and elevated liver enzymes), nerve damage, high blood pressure and problems with blood clotting and wound healing. Blood work is monitored during the time people are taking targeted therapy.

General Side Effects

There are certain side effects that may occur across different treatment approaches. Following are tips for managing these side effects. Your health care team may have additional guidance for your specific treatment type.

Managing Digestive Tract Symptoms Nausea and vomiting

• Eat small, frequent meals.
• Avoid food with strong odors, as well as overly sweet, greasy, fried or highly seasoned food.
• Eat meals cold or at room temperature, which often makes food more easily tolerated.
• Having something in your stomach when you take medication may help ease nausea.

Diarrhea

• Drink plenty of water. Ask your doctor about using drinks such as Gatorade, which provide electrolytes. Electrolytes are body salts that must stay in balance for cells to work properly.
• Over-the-counter medicines such as loperamide (Imodium A-D and others) and prescription drugs are available for diarrhea but should be used only if necessary and with your health care team’s knowledge and approval. If the diarrhea is bad enough that you need medicine, contact a member of your health care team.
• Choose foods that contain soluble fiber, like beans, oat cereals and flaxseed, and high-pectin foods such as peaches, apples, oranges, bananas and apricots.
• Avoid food high in refined sugar and those sweetened with sugar alcohols such as sorbitol and mannitol.

Loss of appetite

• Eating small meals throughout the day is an easy way to take in more protein and calories, which will help maintain your weight. Try to include protein in every meal. Nutrition shakes or protein drinks are a way to add calories to your daily diet.

• To keep from feeling full early, avoid liquids with meals or take only small sips (unless you need liquids to help swallow). Drink most of your liquids between meals.

• Keep high-calorie, high-protein snacks on hand such as hard-boiled eggs, peanut butter, cheese, ice cream, granola bars, liquid nutritional supplements, puddings, nuts, canned tuna and trail mix.

• If you are struggling to maintain your appetite, talk to your health care team about whether appetite-building medication could be right for you.

Managing Pain

There are a number of options for pain relief, including prescription and over-the-counter medications. It’s important to talk to a member of your health care team before taking any over-the-counter medication to determine if it is safe and will not interfere with your treatment. Many pain medications can lead to constipation. Your doctor can recommend over-the-counter or prescription medications that help to avoid or manage constipation.

Physical therapy, acupuncture and massage may also be of help in managing your pain. Consult with a member of your health care team before beginning any of these activities.

Managing Fatigue

Fatigue (extreme tiredness not helped by sleep) is one of the most common side effects of many cancer treatments. If you are very fatigued while on treatment, your doctor may lower the dose of the drug(s), as long as it does not make the treatment less effective. If you are experiencing fatigue, talk to your doctor about whether taking a smaller dose is right for you.

There are a number of other tips for reducing fatigue:

• Take several short naps or breaks during the day.

• Take walks or do some light exercise, if possible.

• Try easier or shorter versions of the activities you enjoy.

• Ask your family or friends to help you with tasks you find difficult or tiring.

There are also prescription medications that may help, such as modafinil. Your health care team can provide guidance on whether medication is the right approach for your individual circumstances.

Q. What are the risk factors for developing BCC or SCC?

A: The major cause of BCC and SCC is unprotected exposure to ultraviolet (UV) radiation from the sun or indoor tanning. Other factors that increase the risk of developing BCC or SCC include:

• History of skin cancer
• Age 50 or older
• Male gender
• Fair skin
• Prior radiation treatment
• Smoking increases the risk of developing SCC, especially on the lips.

Additionally, people whose immune systems are weakened as the result of a medical condition have a higher likelihood of developing certain types of skin cancer, including SCC and melanoma (the most serious form of skin cancer). Some drugs can also weaken the immune system and lead to a higher risk of developing skin cancer, such as large doses of corticosteroids and the drugs given after an organ transplant to help prevent the body from rejecting the new organ.

Q. What is Gorlin syndrome?

A: Gorlin syndrome, also called basal cell nevus syndrome or nevoid basal cell carcinoma syndrome, is a rare inherited condition. People with Gorlin syndrome develop many basal cell carcinomas over their lifetime, often starting in childhood or in their teen years. Unprotected exposure to ultraviolet (UV) radiation from the sun or indoor tanning can increase the incidence of these tumors.

Q. What is a treatment summary and why is important?

A: A treatment summary is a document that you create and keep in your possession. Maintaining your own records allows you and your family members to have instant access to the specifics of your skin cancer diagnosis and treatment. A treatment summary should include:

• Your name and date of birth.
• Date of diagnosis.
• Prescribed therapy/therapies, including dates started and stopped and dosages when appropriate.
• Dates and types of post-diagnosis testing, and the results of these tests.
• Other medications and supplements you are taking.
• Names, affiliations and contact information of all members of your health care team.

Talk to your doctor or a member of your health care team about your intention to create a treatment summary, and ask what else they suggest be included. Take your treatment summary with you when you visit any doctor, not just your oncologist or dermatologist.

Q. What is an actinic keratosis?

A: An actinic keratosis (also known as a solar keratosis) is a rough, scaly patch on the skin that develops after years of sun exposure. It can develop in a number of places, including the face, lips, ears, neck or the back of the hands. If untreated, there is an approximate 5% to 10% risk of an actinic keratosis turning into squamous cell skin cancer.

Treatment options include:

• Medicated gels such as fluorouracil, imiquimod, ingenol mebutate or diclofenac.
• Curettage (scraping), the use of a device called a curet to scrape off damaged cells.
• Cryotherapy, in which the actinic keratosis is destroyed by spraying it with liquid nitrogen.
• Photodynamic therapy, which uses a chemical solution and a special light to destroy the actinic keratosis.
• The use of a laser device to destroy the actinic keratosis, allowing new skin to appear.