Basal Cell Carcinoma

  • Dana-Farber/Brigham and Women's Cancer Care

    Basal cell carcinoma is a type of skin cancer that arises from the basal cells, which are small round cells found in the lower part of the epidermis, the outer layer of the skin. Learn about basal cell carcinoma and find information on how we support and care for people with basal cell carcinoma before, during, and after treatment.

Skin Cancer Treatment at the Center for Cutaneous Oncology 

At the Center for Cutaneous Oncology, we believe that each case of skin cancer is as unique as the individual facing the diagnosis. Experts from a wide variety of medical fields are here to evaluate and treat your particular skin cancer, no matter how rare or complex.

As a patient in the Center for Cutaneous Oncology, you will be cared for by a dedicated team that focuses exclusively on skin cancers. Our experts include dermatologic oncologists, dermatopathologists, medical oncologists, surgical oncologists, radiation oncologists, radiologists, and other specialists.

Our skin cancer specialists work together, and with you, to create individualized treatment that supports all your medical, nutritional, and emotional needs.

Our clinicians are experts in treating all types of skin cancer, including: 

  • Cutaneous T cell and B cell lymphoma (CTCL, CBCL)
  • Merkel cell carcinoma (MCC)
  • Basal cell carcinoma  (BCC)
  • Squamous cell carcinoma  (SCC)
  • Rare adnexal neoplasms:  eccrine, apocrine, sebaceous, and hair follicle tumors
  • Other rare cutaneous cancers

We also treat cutaneous complications of therapy for cancers in general, including:

  • Graft-versus-host disease (GVHD)
  • Skin reactions to cancer chemotherapy

Learn more about skin cancer treatment at the Center for Cutaneous Oncology  

Contact us 

New patients 

If you have never been seen before at Dana-Farber/Brigham and Women's Cancer Center, please call 877-442-3324 or use this online form to make an appointment.

Established patients: 617-632-6571 

Referring physicians: 617-632-6869 

Fax: 617-632-6727 

Mohs Micrographic Surgery Center 

Phone: 617-983-4626 

Fax: 617-983-4504 

Information for: Patients | Healthcare Professionals

General Information About Skin Cancer

Skin cancer is a disease in which malignant (cancer) cells form in the tissues of the skin.

The skin is the body’s largest organ. It protects against heat, sunlight, injury, and infection. Skin also helps control body temperature and stores water, fat, and vitamin D. The skin has several layers, but the two main layers are the epidermis (upper or outer layer) and the dermis (lower or inner layer). Skin cancer begins in the epidermis, which is made up of three kinds of cells:

  • Squamous cells: Thin, flat cells that form the top layer of the epidermis.
  • Basal cells: Round cells under the squamous cells.
  • Melanocytes: Cells that make melanin and are found in the lower part of the epidermis. Melanin is the pigment that gives skin its natural color. When skin is exposed to the sun, melanocytes make more pigment and cause the skin to darken.
Skin anatomy; drawing shows layers of the epidermis, dermis, and subcutaneous tissue including hair shafts and follicles, oil glands, lymph vessels, nerves, fatty tissue, veins, arteries, and a sweat gland. 
Anatomy of the skin, showing the epidermis, dermis, and subcutaneous tissue.

Skin cancer can occur anywhere on the body, but it is most common in skin that is often exposed to sunlight, such as the face, neck, hands, and arms.

There are different types of cancer that start in the skin.

The most common types are basal cell carcinoma and squamous cell carcinoma, which are nonmelanoma skin cancers. Nonmelanoma skin cancers rarely spread to other parts of the body. Melanoma is the rarest form of skin cancer. It is more likely to invade nearby tissues and spread to other parts of the body. Actinic keratosis is a skin condition that sometimes becomes squamous cell carcinoma.

This summary is about nonmelanoma skin cancer and actinic keratosis. See the following PDQ summaries for information on melanoma and other kinds of cancer that affect the skin:

  • Melanoma Treatment
  • Mycosis Fungoides and the Sézary Syndrome Treatment
  • Kaposi Sarcoma Treatment
  • Merkel Cell Carcinoma Treatment
  • Unusual Cancers of Childhood
  • Genetics of Skin Cancer

Skin color and being exposed to sunlight can increase the risk of nonmelanoma skin cancer and actinic keratosis.

Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for basal cell carcinoma and squamous cell carcinoma include the following:

  • Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) over long periods of time.
  • Having a fair complexion, which includes the following:
    • Fair skin that freckles and burns easily, does not tan, or tans poorly.
    • Blue or green or other light-colored eyes.
    • Red or blond hair.
     
  • Having actinic keratosis.
  • Past treatment with radiation.
  • Having a weakened immune system.
  • Having certain changes in the genes that are linked to skin cancer.
  • Being exposed to arsenic.

Risk factors for actinic keratosis include the following:

  • Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) over long periods of time.
  • Having a fair complexion, which includes the following:
    • Fair skin that freckles and burns easily, does not tan, or tans poorly.
    • Blue or green or other light-colored eyes.
    • Red or blond hair.
     

Nonmelanoma skin cancer and actinic keratosis often appear as a change in the skin.

Not all changes in the skin are a sign of nonmelanoma skin cancer or actinic keratosis. Check with your doctor if you notice any changes in your skin.

Possible signs of nonmelanoma skin cancer include the following:

  • A sore that does not heal.
  • Areas of the skin that are:
    • Raised, smooth, shiny, and look pearly.
    • Firm and look like a scar, and may be white, yellow, or waxy.
    • Raised, and red or reddish-brown.
    • Scaly, bleeding or crusty.
     

Possible signs of actinic keratosis include the following:

  • A rough, red, pink, or brown, raised, scaly patch on the skin that may be flat or raised.
  • Cracking or peeling of the lower lip that is not helped by lip balm or petroleum jelly.

Tests or procedures that examine the skin are used to detect (find) and diagnose nonmelanoma skin cancer and actinic keratosis.

The following procedures may be used:

  • Skin exam: A doctor or nurse checks the skin for bumps or spots that look abnormal in color, size, shape, or texture.
  • Skin biopsy: All or part of the abnormal-looking growth is cut from the skin and viewed under a microscope by a pathologist to check for signs of cancer. There are four main types of skin biopsies:
    • Shave biopsy: A sterile razor blade is used to “shave-off” the abnormal-looking growth.
    • Punch biopsy: A special instrument called a punch or a trephine is used to remove a circle of tissue from the abnormal-looking growth.
      Punch biopsy; drawing shows a hollow, circular scalpel being inserted into a lesion on the skin of a patient’s forearm. The instrument is turned clockwise and counterclockwise to cut into the skin and a small sample of tissue is removed to be checked under a microscope. The pullout shows that the instrument cuts down about 4 millimeters (mm) to the layer of fatty tissue below the dermis.  
      Punch biopsy. A hollow, circular scalpel is used to cut into a lesion on the skin. The instrument is turned clockwise and counterclockwise to cut down about 4 millimeters (mm) to the layer of fatty tissue below the dermis. A small sample of tissue is removed to be checked under a microscope. Skin thickness is different on different parts of the body.
    • Incisional biopsy: A scalpel is used to remove part of a growth.
    • Excisional biopsy: A scalpel is used to remove the entire growth.
     

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) depends mostly on the stage of the cancer and the type of treatment used to remove the cancer.

Treatment options depend on the following:

  • The stage of the cancer (whether it has spread deeper into the skin or to other places in the body).
  • The type of cancer.
  • The size of the tumor and what part of the body it affects.
  • The patient’s general health.

Stages of Skin Cancer

After nonmelanoma skin cancer has been diagnosed, tests are done to find out if cancer cells have spread within the skin or to other parts of the body.

The process used to find out if cancer has spread within the skin or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment.

The following tests and procedures may be used in the staging process:

  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Lymph nodebiopsy: For squamous cell carcinoma, the lymph nodes may be removed and checked to see if cancer has spread to them.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

  • Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
  • Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if skin cancer spreads to the lung, the cancer cells in the lung are actually skin cancer cells. The disease is metastatic skin cancer, not lung cancer.

Staging of nonmelanoma skin cancer depends on whether the tumor has certain "high-risk" features and if the tumor is on the eyelid.

Staging for nonmelanoma skin cancer that is on the eyelid is different from staging for nonmelanoma skin cancer that affects other parts of the body.

Millimeters; drawing shows millimeters (mm) using everyday objects. A sharp pencil point shows 1 mm, a new crayon point shows 2 mm, and a new pencil-top eraser shows 5 mm.  
Millimeters (mm). A sharp pencil point is about 1 mm, a new crayon point is about 2 mm, and a new pencil eraser is about 5 mm.

The following are high-risk features for nonmelanoma skin cancer that is not on the eyelid:

  • The tumor is thicker than 2 millimeters.
  • The tumor is described as Clark level IV (has spread into the lower layer of the dermis) or Clark level V (has spread into the layer of fat below the skin).
  • The tumor has grown and spread along nerve pathways.
  • The tumor began on an ear or on a lip that has hair on it.
  • The tumor has cells that look very different from normal cells under a microscope.

The following stages are used for nonmelanoma skin cancer that is not on the eyelid:

Stage 0 (Carcinoma in Situ)

Stage 0 nonmelanoma skin carcinoma in situ; drawing shows skin anatomy with abnormal cells in the epidermis (outer layer of the skin). Also shown are the dermis (inner layer of the skin) and subcutaneous tissue below the dermis. 
Stage 0 nonmelanoma skin carcinoma in situ. Abnormal cells are shown in the epidermis (outer layer of the skin).

In stage 0, abnormalcells are found in the squamous cell or basal cell layer of the epidermis (topmost layer of the skin). These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Tumor size compared to everyday objects; shows various measurements of a tumor compared to a pea, peanut, walnut, and lime 
Pea, peanut, walnut, and lime show tumor sizes.

Stage I

Stage I nonmelanoma skin cancer; drawing shows a tumor in the epidermis (outer layer of the skin) that is no more than 2 centimeters wide. Also shown are the dermis (inner layer of the skin) and the subcutaneous tissue below the dermis. 
Stage I nonmelanoma skin cancer. The tumor is no more than 2 centimeters.

In stage I, cancer has formed. The tumor is not larger than 2 centimeters at its widest point and may have one high-risk feature.

Stage II

Stage II nonmelanoma skin cancer; drawing shows a tumor that is more than 2 centimeters wide that has spread from the epidermis (outer layer of the skin) into the dermis (inner layer of the skin). Also shown is the subcutaneous tissue below the dermis. 
Stage II nonmelanoma skin cancer. The tumor is more than 2 centimeters wide.

In stage II, the tumor is either:

  • larger than 2 centimeters at its widest point; or
  • any size and has two or more high-risk features.

Stage III

In stage III:

  • The tumor has spread to the jaw, eye socket, or side of the skull. Cancer may have spread to one lymph node on the same side of the body as the tumor. The lymph node is not larger than 3 centimeters.
Stage III nonmelanoma skin cancer (1); drawing shows a primary tumor in one arm and parts of the body where it may spread, including the bones of the jaw, eye socket, or side of the skull. 
Stage III nonmelanoma skin cancer (1). Cancer has spread from the primary tumor to bones of the jaw, eye socket, or side of the skull.

or  

  • Cancer has spread to one lymph node on the same side of the body as the tumor. The lymph node is not larger than 3 centimeters and one of the following is true:
    • the tumor is not larger than 2 centimeters at its widest point and may have one high-risk feature; or
    • the tumor is larger than 2 centimeters at its widest point; or
    • the tumor is any size and has two or more high-risk features.
     
Stage III nonmelanoma skin cancer (2); drawing shows a primary tumor in one arm and cancer in a lymph node on the same side of the body as the primary tumor.  Insets show 2 centimeters is about the size of a peanut and 3 centimeters is about the size of a grape. 
Stage III nonmelanoma skin cancer (2). Cancer has spread to one lymph node that is 3 centimeters or smaller and is on the same side of the body as the primary tumor. Also, the tumor is 2 centimeters or smaller at its widest point and may have one high-risk feature; OR the tumor is larger than 2 centimeters at its widest point; OR the tumor is any size and has two or more high-risk features. There are five high-risk features: (1) the tumor is thicker than 2 millimeters; (2) the tumor has spread into the lower layer of the skin or into the layer of fat below the skin; (3) the tumor has grown and spread along nerve pathways; (4) the tumor began on an ear or on a lip that has hair on it; and (5) the tumor has cells that look very different from normal cells under a microscope.

Stage IV

In stage IV, one of the following is true:

  • The tumor is any size and may have spread to the jaw, eye socket, or side of the skull. Cancer has spread to one lymph node on the same side of the body as the tumor and the affected node is larger than 3 centimeters but not larger than 6 centimeters, or cancer has spread to more than one lymph node on one or both sides of the body and the affected nodes are not larger than 6 centimeters; or
  • The tumor is any size and may have spread to the jaw, eye socket, skull, spine, or ribs. Cancer has spread to one lymph node that is larger than 6 centimeters; or
    Stage IV nonmelanoma skin cancer (1); drawing shows a primary tumor in one arm with cancer in a lymph node on the same side of the body as the primary tumor.  Insets show 3 centimeters is about the size of a grape and 6 centimeters is about the size of an egg. 
    Stage IV nonmelanoma skin cancer (1). The tumor is any size. Cancer has spread to one lymph node that is larger than 3 centimeters but not larger than 6 centimeters and is on the same side of the body as the tumor; OR to more than one lymph node 6 centimeters or smaller on one or both sides of the body; OR to one lymph node that is larger than 6 centimeters.
  • The tumor is any size and has spread to the base of the skull, spine, or ribs. Cancer may have spread to the lymph nodes; or
  • Cancer has spread to other parts of the body, such as the lung.
    Stage IV nonmelanoma skin cancer (2); drawing shows a primary tumor in one arm and parts of the body where it may spread, such as the ribs, base of skull, spine, or lung. An inset shows cancer spreading through the blood and lymph nodes to other parts of the body. 
    Stage IV nonmelanoma skin cancer (2). The tumor is any size and has spread to the base of the skull, spine, ribs, lung, or other parts of the body.

The following stages are used for nonmelanoma skin cancer on the eyelid:

Stage 0 (Carcinoma in Situ)

In stage 0, abnormalcells are found in the epidermis (topmost layer of the skin). These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Stage I

Stage I is divided into stages IA, IB, and IC.

  • Stage IA: The tumor is 5 millimeters or smaller and has not spread to the connective tissue of the eyelid or to the edge of the eyelid where the lashes are.
  • Stage IB: The tumor is larger than 5 millimeters but not larger than 10 millimeters or has spread to the connective tissue of the eyelid or to the edge of the eyelid where the lashes are.
  • Stage IC: The tumor is larger than 10 millimeters but not larger than 20 millimeters or has spread through the full thickness of the eyelid.

Stage II

In stage II, one of the following is true:

  • The tumor is larger than 20 millimeters.
  • The tumor has spread to nearby parts of the eye or eye socket.
  • The tumor has spread to spaces around the nerves in the eyelid.

Stage III

Stage III is divided into stages IIIA, IIIB, and IIIC.

  • Stage IIIA: To remove all of the tumor, the whole eye and part of the optic nerve must be removed. The bone, muscles, fat, and connective tissue around the eye may also be removed.
  • Stage IIIB: The tumor may be anywhere in or near the eye and has spread to nearby lymph nodes.
  • Stage IIIC: The tumor has spread to structures around the eye or in the face, or to the brain, and cannot be removed in surgery.

Stage IV

The tumor has spread to distant parts of the body.

Treatment is based on the type of nonmelanoma skin cancer or other skin condition diagnosed:

Basal cell carcinoma

 

Photograph showing a skin cancer lesion that looks reddish brown and slightly raised. 
A skin cancer lesion that looks reddish brown and slightly raised.

 

 

Photograph showing the back of a person’s ear with a skin cancer lesion that looks like an open sore with a pearly rim. 
A skin cancer lesion that looks like an open sore with a pearly rim.

 

Basal cell carcinoma is the most common type of skin cancer. It usually occurs on areas of the skin that have been in the sun, most often the nose. Often this cancer appears as a raised bump that looks smooth and pearly. Another type looks like a scar and is flat and firm and may be white, yellow, or waxy. Basal cell carcinoma may spread to tissues around the cancer, but it usually does not spread to other parts of the body.

Squamous cell carcinoma

 

Photograph showing the side of a person’s face with a skin cancer lesion that looks raised and crusty. 
A skin cancer lesion that looks raised and crusty.

 

 

Photograph showing a person’s leg with a skin cancer lesion that looks pink and raised. 
A skin cancer lesion that looks pink and raised.

 

Squamous cell carcinoma occurs on areas of the skin that have been in the sun, such as the ears, lower lip, and the back of the hands. Squamous cell carcinoma may also appear on areas of the skin that have been burned or exposed to chemicals or radiation. Often this cancer appears as a firm red bump. The tumor may feel scaly, bleed, or form a crust. Squamous cell tumors may spread to nearby lymph nodes. Squamous cell carcinoma that has not spread can usually be cured.

Actinic keratosis

Actinic keratosis is a skin condition that is not cancer, but sometimes changes into squamous cell carcinoma. It usually occurs in areas that have been exposed to the sun, such as the face, the back of the hands, and the lower lip. It looks like rough, red, pink, or brown scaly patches on the skin that may be flat or raised, or the lower lip cracks and peels and is not helped by lip balm or petroleum jelly.

Treatment Option Overview

There are different types of treatment for patients with nonmelanoma skin cancer and actinic keratosis.

Different types of treatment are available for patients with nonmelanoma skin cancer and actinic keratosis. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Five types of standard treatment are used:

Surgery

One or more of the following surgical procedures may be used to treat nonmelanoma skin cancer or actinic keratosis:

  • Mohs micrographic surgery: The tumor is cut from the skin in thin layers. During surgery, the edges of the tumor and each layer of tumor removed are viewed through a microscope to check for cancer cells. Layers continue to be removed until no more cancer cells are seen. This type of surgery removes as little normal tissue as possible and is often used to remove skin cancer on the face.
    Mohs surgery; drawing shows a patient with skin cancer on the face. The pullout shows a block of skin with cancer in the epidermis (outer layer of the skin) and the dermis (inner layer of the skin). A visible lesion is shown on the skin’s surface. Four numbered blocks show the removal of thin layers of the skin one at a time until all the cancer is removed. 
    Mohs surgery. A surgical procedure to remove skin cancer in several steps. First, a thin layer of cancerous tissue is removed. Then, a second thin layer of tissue is removed and viewed under a microscope to check for cancer cells. More layers are removed one at a time until the tissue viewed under a microscope shows no remaining cancer. This type of surgery is used to remove as little normal tissue as possible and is often used to remove skin cancer on the face.
  • Simple excision: The tumor is cut from the skin along with some of the normal skin around it.
  • Shave excision: The abnormal area is shaved off the surface of the skin with a small blade.
  • Electrodesiccation and curettage: The tumor is cut from the skin with a curette (a sharp, spoon-shaped tool). A needle-shaped electrode is then used to treat the area with an electric current that stops the bleeding and destroys cancer cells that remain around the edge of the wound. The process may be repeated one to three times during the surgery to remove all of the cancer.
  • Cryosurgery: A treatment that uses an instrument to freeze and destroy abnormaltissue, such as carcinoma in situ. This type of treatment is also called cryotherapy.
    Cryosurgery; drawing shows an instrument with a nozzle held over an abnormal area on the lower arm of a patient. Inset shows a spray of liquid nitrogen or liquid carbon dioxide coming from the nozzle and covering the abnormal lesion. Freezing destroys the lesion. 
    Cryosurgery. An instrument with a nozzle is used to spray liquid nitrogen or liquid carbon dioxide to freeze and destroy abnormal tissue.
  • Laser surgery: A surgical procedure that uses a laser beam (a narrow beam of intense light) as a knife to make bloodless cuts in tissue or to remove a surface lesion such as a tumor.
  • Dermabrasion: Removal of the top layer of skin using a rotating wheel or small particles to rub away skin cells.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiationtherapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Chemotherapy for nonmelanoma skin cancer and actinic keratosis is usually topical (applied to the skin in a cream or lotion). The way the chemotherapy is given depends on the condition being treated.

Retinoids (drugs related to vitamin A) are sometimes used to treat squamous cell carcinoma of the skin.

See Drugs Approved for Basal Cell Carcinoma for more information.

Photodynamic therapy

Photodynamic therapy (PDT) is a cancer treatment that uses a drug and a certain type of laser light to kill cancer cells. A drug that is not active until it is exposed to light is injected into a vein. The drug collects more in cancer cells than in normal cells. For skin cancer, laser light is shined onto the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue.

Biologic therapy

Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Interferon and imiquimod are biologic agents used to treat skin cancer. Interferon (by injection) may be used to treat squamous cell carcinoma of the skin. Topical imiquimod therapy (a cream applied to the skin) may be used to treat some small basal cell carcinomas.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Basal cell carcinoma and squamous cell carcinoma are likely to recur (come back), usually within 5 years, or new tumors may form. Talk to your doctor about how often you should have your skin checked for signs of cancer.

Treatment Options for Nonmelanoma Skin Cancer

Basal Cell Carcinoma

Treatment of basal cell carcinoma may include the following:

  • Simple excision.
  • Mohs micrographic surgery.
  • Radiation therapy.
  • Electrodesiccation and curettage.
  • Cryosurgery.
  • Photodynamic therapy.
  • Topical chemotherapy.
  • Topicalbiologic therapy with imiquimod.
  • Laser surgery.

Treatment of recurrent basal cell carcinoma is usually Mohs micrographic surgery.

Treatment of basal cell carcinoma that is metastatic or cannot be treated with local therapy is usually chemotherapy or a clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with basal cell carcinoma of the skin. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Squamous Cell Carcinoma

Treatment of squamous cell carcinoma may include the following:

  • Simple excision.
  • Mohs micrographic surgery.
  • Radiation therapy.
  • Electrodesiccation and curettage.
  • Cryosurgery.

Treatment of recurrent squamous cell carcinoma may include the following:

  • Simple excision.
  • Mohs micrographic surgery.
  • Radiation therapy.

Treatment of squamous cell carcinoma that is metastatic or cannot be treated with local therapy may include the following:

  • Chemotherapy.
  • Retinoidtherapy and biologic therapy with interferon.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with squamous cell carcinoma of the skin. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Treatment Options for Actinic Keratosis

Actinic keratosis is not cancer but is treated because it may develop into cancer. Treatment of actinic keratosis may include the following:

  • Topical chemotherapy.
  • Topicalbiologic therapy with imiquimod.
  • Cryosurgery.
  • Electrodesiccation and curettage.
  • Dermabrasion.
  • Shave excision.
  • Photodynamic therapy.
  • Laser surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with actinic keratosis. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About Skin Cancer

For more information from the National Cancer Institute about skin cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on February 7, 2014.


General Information About Skin Cancer

There are three main types of skin cancer:

  • Basal cell carcinoma (BCC).
  • Squamous cell carcinoma (SCC).
  • Melanoma.

BCC and SCC are the most common forms of skin cancer and are collectively referred to as nonmelanoma skin cancers. This summary only covers the treatment of nonmelanoma skin cancers. (Refer to the PDQ summary on Melanoma Treatment for more information.)

Incidence and Mortality

Nonmelanoma skin cancer is the most commonly occurring cancer in the United States. BCC is the more common type of the two nonmelanoma types, accounting for about three-quarters of nonmelanoma skin cancers.[1] The incidence of nonmelanoma skin cancer appears to be increasing in some,[2] but not all [3] areas of the United States. Overall U.S. incidence rates have likely been increasing for a number of years.[4] At least some of this increase may be attributable to increasing skin cancer awareness and resulting increasing investigation and biopsy of skin lesions.

Precise estimation of the total numbers and incidence rate of nonmelanoma skin cancer is not possible because reporting to cancer registries is not required. However, based on Medicare fee-for-service data, which were then extrapolated to the U.S. population, an estimated 2,152,500 persons were treated for nonmelanoma skin cancers in 2006.[4] That number would exceed all other cases of cancer estimated by the American Cancer Society for that year, which was about 1.4 million.[5] Although the two types of nonmelanoma skin cancer are the most common of all malignancies, they account for less than 0.1% of patient deaths caused by cancer.

Risk Factors

Epidemiologic evidence suggests that exposure to ultraviolet (UV) radiation and the sensitivity of an individual’s skin to UV radiation are risk factors for skin cancer, though the type of exposure (i.e., high-intensity exposure and short-duration exposure vs. chronic exposure) and pattern of exposure (i.e., continuous pattern vs. intermittent pattern) may differ among the three main skin cancer types.[6][7][8] All three types of skin cancer are more likely to occur in individuals of light complexion who have had substantial exposure to sunlight, and skin cancers are more common in the southern latitudes of the Northern hemisphere. In addition, the immune system may play a role in pathogenesis of skin cancers.

Organ transplant recipients receiving immunosuppressive drugs are at an elevated risk of skin cancers, particularly SCC. Arsenic exposure also increases the risk of cutaneous SCC.[1] Serologic evidence from a population-based case-control study has shown a possible association between infection with the human papilloma virus (HPV) genus beta-species 1 and SCC.[9][10]

Related Summaries

Note: Other PDQ summaries containing information related to skin cancer include the following:

  • Skin Cancer Prevention
  • Skin Cancer Screening
  • Unusual Cancers of Childhood (skin cancer in children)

References:

  1. Reszko A, Aasi SZ, Wilson LD, et al.: Cancer of the skin. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1610-33.

  2. Athas WF, Hunt WC, Key CR: Changes in nonmelanoma skin cancer incidence between 1977-1978 and 1998-1999 in Northcentral New Mexico. Cancer Epidemiol Biomarkers Prev 12 (10): 1105-8, 2003.

  3. Harris RB, Griffith K, Moon TE: Trends in the incidence of nonmelanoma skin cancers in southeastern Arizona, 1985-1996. J Am Acad Dermatol 45 (4): 528-36, 2001.

  4. Rogers HW, Weinstock MA, Harris AR, et al.: Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol 146 (3): 283-7, 2010.

  5. American Cancer Society.: Cancer Facts and Figures 2006. Atlanta, Ga: American Cancer Society, 2006. Also available online. Last accessed February 21, 2014.

  6. Koh HK: Cutaneous melanoma. N Engl J Med 325 (3): 171-82, 1991.

  7. Preston DS, Stern RS: Nonmelanoma cancers of the skin. N Engl J Med 327 (23): 1649-62, 1992.

  8. English DR, Armstrong BK, Kricker A, et al.: Case-control study of sun exposure and squamous cell carcinoma of the skin. Int J Cancer 77 (3): 347-53, 1998.

  9. Karagas MR, Nelson HH, Sehr P, et al.: Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin. J Natl Cancer Inst 98 (6): 389-95, 2006.

  10. Patel AS, Karagas MR, Perry AE, et al.: Exposure profiles and human papillomavirus infection in skin cancer: an analysis of 25 genus beta-types in a population-based study. J Invest Dermatol 128 (12): 2888-93, 2008.

Cellular Classification of Skin Cancer

This evidence summary covers basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin, and the related noninvasive lesion actinic keratosis (viewed by some pathologists as a variant of in situ SCC ).[1] Although BCC and SCC are by far the most frequent types of nonmelanoma skin cancers, approximately 82 types of skin malignancies, with a wide range of clinical behaviors, fall into the category of nonmelanoma skin cancer.[2] Other types of malignant disease of the skin include the following:

  • Melanoma (as noted above).
  • Cutaneous T-cell lymphomas (e.g., mycosis fungoides).
  • Kaposi sarcoma.
  • Extramammary Paget disease.
  • Apocrine carcinoma of the skin.
  • Metastatic malignancies from various primary sites.

(Refer to the PDQ summaries on Melanoma Treatment, Merkel Cell Carcinoma Treatment, Mycosis Fungoides and the Sézary Syndrome Treatment, and Kaposi Sarcoma Treatment for more information.)

BCC and SCC are both of epithelial origin. They are usually diagnosed on the basis of routine histopathology obtained from a shave, punch, or fusiform excisional biopsy.[1]

Basal Cell Carcinoma

BCC is at least three times more common than SCC in nonimmunocompromised patients. It usually occurs on sun-exposed areas of skin, and the nose is the most frequent site. Although there are many different clinical presentations for BCC, the most characteristic type is the asymptomatic nodular or nodular ulcerative lesion that is elevated from the surrounding skin, has a pearly quality, and contains telangiectatic vessels.

BCC has a tendency to be locally destructive. High-risk areas for tumor recurrence after initial treatment include the central face (e.g., periorbital region, eyelids, nasolabial fold, or nose-cheek angle), postauricular region, pinna, ear canal, forehead, and scalp.[3] A specific subtype of BCC is the morpheaform type. This subtype typically appears as a scar-like, firm plaque. Because of indistinct clinical tumor margins, the morpheaform type is difficult to treat adequately with traditional treatments.[4]

BCCs are composed of nonkeratinizing cells derived from the basal cell layer of the epidermis. They are slow growing and rarely metastasize. However, they can result in serious deforming damage locally if left untreated or if local recurrences cannot be completely excised. BCCs often have a characteristic mutation in the patched 1 tumor suppressor gene (PTCH1), although the mechanism of carcinogenesis is not clear.[1]

Squamous Cell Carcinoma

SCCs also tend to occur on sun-exposed portions of the skin, such as the ears, lower lip, and dorsa of the hands. However, SCCs that arise in areas of non–sun-exposed skin or that originate de novo on areas of sun-exposed skin are prognostically worse because they have a greater tendency to metastasize than those that occur on sun-exposed skin that develop from actinic keratosis. People with chronic sun damage, sites of prior burns, arsenic exposure, chronic cutaneous inflammation as seen in longstanding skin ulcers, and sites of previous x-ray therapy are predisposed to the development of SCC.[4]

SCCs are composed of keratinizing cells. These tumors are more aggressive than BCCs and have a range of growth, invasive, and metastatic potential. Prognosis is associated with the degree of differentiation, and tumor grade is reported as part of the staging system.[2] A four-grade system (G1–G4) is most common, but two- and three-grade systems may also be used. Mutations in the PTCH1 tumor suppressor gene have been reported in SCCs removed from patients with a prior history of multiple BCCs.[5]

SCC in situ (also called Bowen disease) is a noninvasive lesion. It may be difficult to distinguish it pathologically from a benign inflammatory process.[1] The risk of development into invasive SCC is low, reportedly in the 3% to 4% range.[6]

Actinic Keratosis

Actinic keratoses are potential precursors of SCC, but the rate of progression is extremely low, and the vast majority do not become SCCs. These typically red, scaly patches usually arise on areas of chronically sun-exposed skin and are likely to be found on the face and dorsal aspects of the hand.

References:

  1. Reszko A, Aasi SZ, Wilson LD, et al.: Cancer of the skin. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1610-33.

  2. Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 301–14.

  3. Dubin N, Kopf AW: Multivariate risk score for recurrence of cutaneous basal cell carcinomas. Arch Dermatol 119 (5): 373-7, 1983.

  4. Wagner RF, Casciato DA: Skin cancers. In: Casciato DA, Lowitz BB, eds.: Manual of Clinical Oncology. 4th ed. Philadelphia, Pa: Lippincott, Williams, and Wilkins, 2000, pp 336-373.

  5. Ping XL, Ratner D, Zhang H, et al.: PTCH mutations in squamous cell carcinoma of the skin. J Invest Dermatol 116 (4): 614-6, 2001.

  6. Kao GF: Carcinoma arising in Bowen's disease. Arch Dermatol 122 (10): 1124-6, 1986.

Stage Information for Skin Cancer

There are separate staging systems in the 7th edition of the American Joint Committee on Cancer’s (AJCC) AJCC Cancer Staging Manual for carcinomas of the eyelid versus other skin surfaces.[1][2] The staging system for non-eyelid skin cancers is primarily designed for squamous cell carcinomas (SCCs). The staging system for carcinoma of the eyelid addresses carcinomas of all histologies.

Basal cell carcinoma (BCC) rarely metastasizes, thus, a metastatic work-up is usually not necessary. Regional lymph nodes should be routinely examined in all cases of SCC, especially for high-risk tumors appearing on the lips, ears, perianal and perigenital regions, or high-risk areas of the hand. In addition, regional lymph nodes should be examined with particular care in cases of SCCs arising in sites of chronic ulceration or inflammation, burn scars, or sites of previous radiation therapy treatment.

Table 2 has a separate list of risk features that should be evaluated for non-eyelid carcinomas; the relevant risk features should also be evaluated for SCCs of the eyelid. Even with relatively small tumor size, SCCs that occur in immunosuppressed patients tend to have more aggressive behavior than SCCs in nonimmunosuppressed patients. Although not a formal part of the AJCC staging system, it is recommended that centers prospectively studying SCC record the presence and type of immunosuppression in addition to the risk features listed in Table 2.

Staging for Cutaneous SCC and Other Cutaneous Carcinomas (Excluding Carcinoma of the Eyelid)

The American Joint Committee on Cancer has designated staging by TNM classification.[1] The TNM classification is used to stage both BCC and SCC.

Table 1. Primary Tumor (T) for Non-Eyelid Carcinomaa,b

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

Tis

Carcinoma in situ.

T1

Tumor ≤2 cm in greatest dimension with <2 high-risk features.c

T2

Tumor >2 cm in greatest dimension.

or

Tumor any size with ≥2 high-risk features.c

T3

Tumor with invasion of maxilla, mandible, orbit, or temporal bone.

T4

Tumor with invasion of skeleton (axial or appendicular) or perineural invasion of skull base.

aReprinted with permission from AJCC: Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 301-14.

bExcludes cutaneous squamous cell carcinoma of the eyelid.

cHigh-risk features for the primary tumor (T) staging.

Table 2. High-Risk Features for Primary Tumor (T) Staging for Non-Eyelid Carcinoma

Depth/invasion

>2 mm thickness (Breslow thickness).

Clark level ≥IV.

Perineural invasion.

Anatomic

Primary site ear.

Location

Primary site hair-bearing lip.

Differentiation

Poorly differentiated or undifferentiated.

aReprinted with permission from AJCC: Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 301-14.

Table 3. Regional Lymph Nodes (N) for Non-Eyelid Carcinomaa

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastases.

N1

Metastasis in a single ipsilateral lymph node, ≤3 cm in greatest dimension.

N2

Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, ≤6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, ≤6 cm in greatest dimension.

N2a

Metastasis in a single ipsilateral lymph node, >3 cm but ≤6 cm in greatest dimension.

N2b

Metastases in multiple ipsilateral lymph nodes, ≤6 cm in greatest dimension.

N2c

Metastases in bilateral or contralateral lymph nodes, ≤6 cm in greatest dimension.

N3

Metastasis in a lymph node, >6 cm in greatest dimension.

aReprinted with permission from AJCC: Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 301-14.

Table 4. Distant Metastasis (M) for Non-Eyelid Carcinomaa

M0

No distant metastases.

M1

Distant metastases.

aReprinted with permission from AJCC: Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 301-14.

Patients with a primary cutaneous SCC or other cutaneous carcinoma with no evidence (i.e., clinical, radiologic, or pathologic) of regional or distant metastases are divided into the following two stages:

  • Stage I for tumors measuring 2 cm or less in size.
  • Stage II for tumors measuring more than 2 cm in size.

In instances where there is clinical concern about extension of the tumor into bone and radiologic evaluation has been performed (and is negative), these data may be included to support the stage I versus stage II designation. Tumors that are 2 cm or less in size can be upstaged to stage II if they contain two or more high-risk features.

Stage III patients are those with either of the following:

  • Clinical, histologic, or radiologic evidence of one involved lymph node measuring 3 cm or less in size.
  • Tumor extension into bone; namely, the maxilla, mandible, orbit, or temporal bone.

Stage IV patients are those with any of the following:

  • Tumor with direct or perineural invasion of skull base or axial skeleton.
  • Two or more involved lymph nodes.
  • Single or multiple involved lymph nodes measuring more than 3 cm in size.
  • Distant metastases.
Table 5. Anatomic Stage/Prognostic Groups for Non-Eyelid Carcinomaa

Stage

T

N

M

0

Tis

N0

M0

I

T1

N0

M0

II

T2

N0

M0

III

T3

N0

M0

T1

N1

M0

T2

N1

M0

T3

N1

M0

IV

T1

N2

M0

T2

N2

M0

T3

N2

M0

Any T

N3

M0

T4

Any N

M0

Any T

Any N

M1

aReprinted with permission from AJCC: Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 301-14.

Staging for Carcinomas of the Eyelid

The AJCC has designated staging by TNM classification.[2] The TNM classification is used to stage all cell types of eyelid carcinomas.

Table 6. Primary Tumor (T) for Eyelid Carcinomaa

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

Tis

Carcinoma in situ.

T1

Tumor ≤5 mm in greatest dimension.

Not invading the tarsal plate or eyelid margin.

T2a

Tumor >5 mm but not >10 mm in greatest dimension.

Or, any tumor that invades the tarsal plate or eyelid margin.

T2b

Tumor >10 mm but not >20 mm in greatest dimension.

Or, involves full thickness eyelid.

T3a

Tumor >20 mm in greatest dimension.

Or, any tumor that invades adjacent ocular or orbital structures.

Any T with perineural tumor invasion.

T3b

Complete tumor resection requires enucleation, exenteration, or bone resection.

T4

Tumor is not resectable because of extensive invasion of ocular, orbital, craniofacial structures, or brain.

aReprinted with permission from AJCC: Carcinoma of the Eyelid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 523-6.

Table 7. Regional Lymph Nodes (N) for Eyelid Carcinomaa

NX

Regional lymph nodes cannot be assessed.

cN0

No regional lymph node metastasis based upon clinical evaluation or imaging.

pN0

No regional lymph node metastasis based upon lymph node biopsy.

N1

Regional lymph node metastasis.

aReprinted with permission from AJCC: Carcinoma of the Eyelid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 523-6.

Table 8. Distant Metastasis (M) for Eyelid Carcinomaa

M0

No distant metastasis.

M1

Distant metastasis.

aReprinted with permission from AJCC: Carcinoma of the Eyelid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 523-6.

Table 9. Anatomic Stage/Prognostic Groups for Eyelid Carcinomaa

Stage 0

Tis

N0

M0

Stage IA

T1

N0

M0

Stage IB

T2a

N0

M0

Stage IC

T2b

N0

M0

Stage II

T3a

N0

M0

Stage IIIA

T3b

N0

M0

Stage IIIB

Any T

N1

M0

Stage IIIC

T4

Any N

M0

Stage IV

Any T

Any N

M1

aReprinted with permission from AJCC: Carcinoma of the Eyelid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 523-6.

References:

  1. Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 301–14.

  2. Carcinoma of the Eyelid. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 523-6.

Basal Cell Carcinoma of the Skin Treatment

There is a wide range of treatment approaches, including excision, radiation therapy, cryosurgery, electrodesiccation and curettage, photodynamic or laser-beam light exposure, and topical therapies. Mohs micrographic surgery is a form of tumor excision that involves progressive radial sectioning and real-time examination of the resection margins until adequate uninvolved margins have been achieved, avoiding wider margins than needed. Each of these methods is useful in specific clinical situations. Depending on case selection, these methods have recurrence-free rates ranging from 85% to 95%.

A systematic review of 27 randomized controlled trials comparing various treatments for BCC has been published.[1] Eighteen of the studies were published in full, and nine were published in abstract form only. Only 19 of the 27 trials were analyzed by intention-to-treat criteria. Because the case fatality rate of BCC is so low, the primary endpoint of most trials is complete response and/or recurrence rate after treatment. Most of the identified studies had short follow-up times (only one study had a follow-up as long as 4 years) and were not of high quality. Short follow-up periods will lead to overestimates of tumor control. A literature review of recurrence rates in case series with long-term follow-up after treatment of BCCs indicated that only 50% of recurrences occurred within the first 2 years, 66% after 3 years, and 18% after 5 years.[2] A rule of thumb was that the 10-year recurrence rates were about double the 2-year recurrence rates.

Treatment for Basal Cell Carcinoma of the Skin

Treatment options include the following:

  1. Excision with margin evaluation.
  2. Mohs micrographic surgery.
  3. Radiation therapy.
  4. Curettage and electrodesiccation.
  5. Cryosurgery.
  6. Photodynamic therapy.
  7. Topical fluorouracil (5-FU).
  8. Imiquimod topical therapy.
  9. Carbon dioxide laser.

Excision with margin evaluation

This traditional surgical treatment usually relies on surgical margins ranging from 3 mm to 10 mm, depending on the diameter of the tumor. Re-excision may be required if the surgical margin is found to be inadequate on permanent sectioning. For example, in one trial, 35 of 199 (18%) primary BCCs were incompletely excised by the initial surgery and underwent a re-excision.[3] In addition, many laboratories examine only a small fraction of the total tumor margin pathologically. Therefore, the declaration of tumor-free margins can be subject to sampling error.[4]

Excision has been compared in randomized trials to radiation therapy, Mohs micrographic surgery, photodynamic therapy (PDT), and cryosurgery:

  • In a single-center trial, 360 patients with facial BCCs less than 4 cm in diameter were randomly assigned to excision or to radiation therapy (55% interstitial brachytherapy, 33% contact radiation therapy, and 12% conventional external-beam radiation therapy [EBRT]).[5] Excisional margins, assessed during surgery by frozen section during the procedure in 91% of cases, had to be at least 2 mm, with re-excision if necessary. Thirteen patients were not treated and were dropped from the analysis.

    At 4 years (mean follow-up of 41 months), the actuarial failure rates (confirmed persistent or recurrent tumor) were 0.7% and 7.5% in the surgery and radiation therapy arms, respectively (P = .003). The cosmetic results were also rated as better after surgery by both patients and dermatologists, and also by three independent judges.[6] At 4 years, 87% of surgery patients rated cosmesis as good versus 69% of radiation therapy patients.[6][Level of evidence: 1iiDii]

  • In a two-center, intent-to-treat analysis, 374 patients with 408 primary facial BCCs were randomly assigned to receive either surgical excision or Mohs micrographic surgery with at least a 3-mm margin around the visible tumor until there were no positive margins in either case.[3]

    After 30 months of follow-up, the recurrence rate was 5 out of 171 tumors (3%) in the excision group and 3 out of 160 (2%) in the Mohs micrographic surgery group (absolute difference = 1%; 95% confidence interval [CI], -2.5%–+3.7%; P = .724). There was no difference in complication rates, and overall cosmetic outcomes were similar. Total operative costs were nearly twice as high in the Mohs group (405.79 Euros vs. 216.86 Euros (P < .001).[3][Level of evidence 1iiDii]

  • In a multicenter, randomized trial, 101 adults with previously untreated nodular skin BCCs, excluding lesions of the midface, orbital areas, and ears, were treated with either excision (at least 5-mm margins) or PDT using topical methyl aminolevulinate cream (160 mg/g) followed by red-light exposure (wavelength 570–670 nm, 75 J/cm2) twice, 7 days apart.[7] A per-protocol–per-lesion analysis was performed on the 97 patients who had an excision or at least one cycle of PDT.

    At 3 months, the complete response (CR) rate in the surgery group was 51 out of 52 lesions (98%) versus 48 out of 53 lesions (91%) in the PDT group (P = .25). CR rates assessed at 12 months were 96% versus 83% (P = .15).[7][Level of evidence: 1iiDiv] The investigators interpreted the results as noninferiority of PDT, but the study may have been underpowered. Both the investigators and the patients, however, rated the cosmetic results as either excellent or good in a higher proportion of PDT treatments at each time point of follow-up. At 12 months, patient ratings of excellent or good were 98% versus 84% (P = .03) and investigator ratings were 79% versus 38% (P = .001).

  • In a randomized, single-center trial, 96 primary BCCs (patient number unclear) less than 2 cm in diameter involving the head and neck area were randomly assigned to excision with a 3-mm safe margin versus cryosurgery (i.e., curettage plus two freeze-thaw cycles by liquid nitrogen spray gun).[8]

    At 1 year, there were no recurrences in the excision group versus three in the cryosurgery group (P = NS), but this is a very short follow-up time. Patients and five independent professionals who were blinded to the treatment arm rated the cosmetic outcomes. Their overall assessments favored excision.[8][Level of evidence 1iiDiv]

Mohs micrographic surgery

Mohs micrographic surgery is a specialized technique used with the intent to achieve the narrowest margins necessary to avoid tumor recurrence, while maximally preserving cosmesis. It is best suited to management of tumors in cosmetically sensitive areas or for tumors that have recurred after initial excision (e.g., eyelid periorbital area, nasolabial fold, nose-cheek angle, posterior cheek sulcus, pinna, ear canal, forehead, scalp, fingers, and genitalia).[9][10] It is also often used to treat tumors with poorly defined clinical borders.

Mohs micrographic surgery requires special training. The tumor is microscopically delineated, with serial radial resection, until it is completely removed as assessed with real-time frozen sections. Noncontrolled case series suggested that the disease control rates were superior to other treatment methods for BCC.[9][11][12] However, as noted in the section on excision, the disease control rate was not clearly better when directly compared to surgical excision of facial BCCs in a randomized trial of primary BCCs.[3]

Radiation therapy

Radiation therapy is particularly useful in the management of patients with primary lesions that would otherwise require difficult or extensive surgery (e.g., nose or ears).[13] Radiation therapy eliminates the need for skin grafting when surgery would result in an extensive defect. Cosmetic results are generally good, with a small amount of hypopigmentation or telangiectasia in the treatment port. Radiation therapy can also be used for lesions that recur after a primary surgical approach.[14] Radiation therapy is avoided in patients with conditions that predispose them to radiation-induced cancers, such as xeroderma pigmentosum or basal cell nevus syndrome.

As noted above, radiation therapy has been compared to excision in a randomized trial that showed better response and cosmesis associated with surgery.[5][6]

In a single-center, randomized trial, radiation was superior to cryotherapy in local control at 2 years in 93 patients with primary BCCs.[15] Patients were randomly assigned to receive either EBRT (130 kV x-rays, dosimetry depending upon lesion size) or cryotherapy (two freeze-thaw cycles with liquid nitrogen by spray gun). Patients with lesions on the nose or ear were excluded, since the investigators felt that electron beam therapy is the treatment of choice in these locations. By 1 year, the recurrence rates in the radiation and cryotherapy arms were 4% and 39%, respectively, in a per-protocol analysis. The investigators did not perform a statistical analysis, but the authors of a systematic literature review calculated a relative risk of 0.11 in favor of radiation (95% CI, 0.03–0.43).[1][Level of evidence 1iiDiv]

Curettage and electrodesiccation

This procedure is also sometimes called electrosurgery. It is a widely employed method for removing primary BCCs, especially superficial lesions of the neck, trunk, and extremities that are considered to be at low risk for recurrence. A sharp curette is used to scrape away the tumor down to its base, followed by electrodesiccation of the lesion base. Although it is a quick method for destroying the tumor, the adequacy of treatment cannot be assessed immediately since the surgeon cannot visually detect the depth of microscopic tumor invasion.

A Cochrane Collaboration systematic review found no randomized trials comparing this treatment method with other approaches.[1] In a large, single-center case series of 2,314 previously untreated BCCs managed at a major skin cancer unit, the 5-year recurrence rate of BCCs of the neck, trunk, and extremities was 3.3%. However, rates increased substantially for tumors larger than 6 mm in diameter at other anatomic sites.[16][Level of evidence 3iiiDii]

Cryosurgery

Cryosurgery may be considered for patients with small, clinically well-defined primary tumors. It is infrequently used for the management of BCC, but may be useful for patients with medical conditions that preclude other types of surgery.

Contraindications include abnormal cold tolerance, cryoglobulinemia, cryofibrinogenemia, Raynaud disease (in the case of lesions on hands and feet), and platelet deficiency disorders. Additional contraindications to cryosurgery include tumors of the scalp, ala nasi, nasolabial fold, tragus, postauricular sulcus, free eyelid margin, upper lip vermillion border, lower legs, and tumors near nerves. Caution should also be used before treating nodular ulcerative neoplasia more than 3 cm in diameter, carcinomas fixed to the underlying bone or cartilage, tumors situated on the lateral margins of the fingers and at the ulnar fossa of the elbow, or recurrent carcinomas following surgical excision.

Edema is common following treatment, especially around the periorbital region, temple, and forehead. Treated tumors usually exude necrotic material after which an eschar forms and persists for about 4 weeks. Permanent pigment loss at the treatment site is unavoidable, so the treatment is not well suited to dark-skinned patients. Atrophy and hypertrophic scarring have been reported as well as instances of motor and sensory neuropathy.

As noted in the section above on radiation therapy, a small 93-patient trial comparing cryosurgery to radiation therapy, with only 1 year of follow-up, showed a statistically significant higher recurrence rate with cryosurgery than radiation (39% vs. 4%).[15]

In a small, single-center, randomized study, 88 patients were assigned to either cryosurgery in two freeze-thaw cycles or PDT using delta-aminolevulinic acid as the photosensitizing agent and 635 nm wavelength light with 60 J/cm2 energy delivered by Nd:YAG laser versus cryosurgery in two freeze-thaw cycles.[17] Overall clinical efficacy was similar in evaluable lesions at 1 year (5/39 recurrences for cryosurgery vs. 2/44 recurrences for PDT), but more re-treatments were needed with PDT to achieve complete responses.[17][Level of evidence 1iiD] Cosmetic outcomes favored PDT (93% good or excellent after PDT vs. 54% after cryosurgery, P < .001). In another randomized study of 118 patients, reported in abstract form only, cryosurgery was compared with PDT with methyl aminolevulinic acid.[18][19] Tumor control rates at 3 years were similar (74%), but cosmetic outcomes were better in the PDT group. These cryosurgery-PDT comparisons were reported on a per-protocol basis rather than an intent-to-treat basis.[18][19][Level of evidence 1iiDiv]

Photodynamic therapy

Photodynamic therapy with photosensitizers is used in the management of a wide spectrum of superficial epithelial tumors.[20] A topical photosensitizing agent such as 5-aminolevulinic acid or methyl aminolevulinate is applied to the tumor, followed by exposure to a specific wavelength of light (whether laser or broad band), depending upon the absorption characteristics of the photosensitizer. In the case of multiple BCCs, short-acting systemic (intravenous) photosensitizers such as verteporfin have been used investigationally.[21] Upon light activation, the photosensitizer reacts with oxygen in the tissue to form singlet oxygen species, resulting in local cell destruction.

In case series, PDT has been associated with high initial CR rates. However, substantial regrowth rates of up to 50% have been reported with long-term follow-up.[20] A randomized trial of PDT versus excision is summarized in the section on simple excision above.[7] Two small trials, one reported in abstract form only, comparing PDT with cryosurgery are summarized in the cryosurgery section above, showing similar antitumor efficacy but better cosmesis with PDT.[17][18][19]

Topical fluorouracil (5-FU)

Topical 5-FU, as a 5% cream, may be useful in specific limited circumstances. It is a Food and Drug Administration (FDA)-approved treatment for superficial BCCs in patients for whom conventional methods are impractical, such as individuals with multiple lesions or difficult treatment sites. Safety and efficacy in other indications have not been established.[22][23][Level of evidence: 3iiiDiv] Given the superficial nature of its effects, nonvisible dermal involvement may persist, giving a false impression of treatment success. In addition, the brisk accompanying inflammatory reaction may cause substantial skin toxicity and discomfort in a large proportion of patients.

Imiquimod topical therapy

Imiquimod is an agonist for the toll-like receptor 7 and/or 8, inducing a helper T-cell cytokine cascade and interferon production. It purportedly acts as an immunomodulator. It is available as a 5% cream and is used in schedules ranging from twice weekly to twice daily over 5 to 15 weeks. Most of the experience is limited to case series of BCCs that are less than 2 cm2 in area and that are not in high-risk locations (i.e., within 1 cm of the hairline, eyes, nose, mouth, ear; or in the anogenital, hand, or foot regions).[23] Follow-up times have also been generally short. Reported CR rates vary widely, from about 40% to 100%.[23][Level of evidence 3iiiDiv]

There have been a number of randomized trials of imiquimod.[24][25][26][27][28][29] However, the designs of all of them make interpretation of long-term efficacy impossible. Most were industry-sponsored dose-finding studies, with small numbers of patients on any given regimen; and patients were only followed for 6 to 12 weeks, with excision at that time to determine histologic response.[Level of evidence 1iDiv] Therefore, although imiquimod is an FDA-approved treatment for superficial BCCs, some investigators in the field do not recommend it for initial monotherapy for BCC; some reserve it for patients with small lesions in low-risk sites who cannot undergo treatment with more established therapies.[23]

Carbon dioxide laser

This method is used very infrequently in the management of BCC because of the difficulty in controlling tumor margins.[30] Few clinicians have extensive experience with the technique for BCC treatment. There are no randomized trials comparing it with other modalities.

Treatment for Recurrent Basal Cell Carcinoma of the Skin

After treatment for BCC, patients should be followed clinically and examined regularly. Most recurrences occur within 5 years, but as noted above, about 18% of recurrences are diagnosed beyond that point.[2] Patients who develop a primary BCC are also at increased risk of subsequent primary skin cancers because the susceptibility of their sun-damaged skin to additional cancers persists.[31][32][33] This effect is sometimes termed field carcinogenesis. Age at diagnosis of the first BCC (<65 years), red hair, and initial BCC on the upper extremities appear to be associated with higher risk of subsequent new BCCs.[34]

Mohs micrographic surgery is commonly used for local recurrences of BCC. In a separate group within a randomized trial comparing excision to Mohs micrographic surgery for primary BCCs, 204 recurrent BCCs were randomly assigned to excision versus Mohs micrographic surgery. The recurrence rates were 8 out of 102 patients and 2 out of 102 patients, respectively, after a mean follow-up of 2.08 years (P = NS).[3][Level of evidence 1iiDii] There were more postoperative complications, including wound infections, graft necrosis, or bleeding in the excision group than the Mohs surgery group (19% vs. 8%, P = .021). As with primary tumors, the operative costs associated with Mohs surgery were higher than with excision (489.06 Euros vs. 323.49 Euros [P = .001]).

Treatment for Metastatic Basal Cell Carcinoma (or Advanced Disease Untreatable by Local Modalities)

Metastatic and far-advanced BCC is rare, and reports of systemic therapy are limited to case reports and very small case series with tumor response as the endpoint.[35][Level of evidence 3iiiDiv] Cisplatin, alone or in combination with other drugs, is the most commonly reported systemic therapy and appears to be associated with the best tumor-response rates.[36][37] A variety of other agents have been reported but have low-associated response rates, including cyclophosphamide, vinblastine, 5-FU, methotrexate, and doxorubicin.[36]

Since there is no standard therapy, clinical trials are appropriate if available. Because BCCs often exhibit constitutive activation of the Hedgehog/PTCH1-signaling pathway, Hedgehog pathway inhibitors are under investigation.[38] An orally administered Hedgehog pathway inhibitor (GDC-0449) has produced objective responses in patients with advanced or metastatic sporadic BCC,[39] and another topical inhibitor has produced objective responses in patients with nevoid basal cell carcinoma syndrome.[40][Level of evidence: 3iiiDiv]

Information about ongoing clinical trials is available from the NCI Web site.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with basal cell carcinoma of the skin. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Bath-Hextall FJ, Perkins W, Bong J, et al.: Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev (1): CD003412, 2007.

  2. Rowe DE, Carroll RJ, Day CL Jr: Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: implications for patient follow-up. J Dermatol Surg Oncol 15 (3): 315-28, 1989.

  3. Smeets NW, Krekels GA, Ostertag JU, et al.: Surgical excision vs Mohs' micrographic surgery for basal-cell carcinoma of the face: randomised controlled trial. Lancet 364 (9447): 1766-72, 2004 Nov 13-19.

  4. Abide JM, Nahai F, Bennett RG: The meaning of surgical margins. Plast Reconstr Surg 73 (3): 492-7, 1984.

  5. Avril MF, Auperin A, Margulis A, et al.: Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer 76 (1): 100-6, 1997.

  6. Petit JY, Avril MF, Margulis A, et al.: Evaluation of cosmetic results of a randomized trial comparing surgery and radiotherapy in the treatment of basal cell carcinoma of the face. Plast Reconstr Surg 105 (7): 2544-51, 2000.

  7. Rhodes LE, de Rie M, Enström Y, et al.: Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial. Arch Dermatol 140 (1): 17-23, 2004.

  8. Thissen MR, Nieman FH, Ideler AH, et al.: Cosmetic results of cryosurgery versus surgical excision for primary uncomplicated basal cell carcinomas of the head and neck. Dermatol Surg 26 (8): 759-64, 2000.

  9. Thomas RM, Amonette RA: Mohs micrographic surgery. Am Fam Physician 37 (3): 135-42, 1988.

  10. Rowe DE, Carroll RJ, Day CL Jr: Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 15 (4): 424-31, 1989.

  11. Malhotra R, Huilgol SC, Huynh NT, et al.: The Australian Mohs database, part II: periocular basal cell carcinoma outcome at 5-year follow-up. Ophthalmology 111 (4): 631-6, 2004.

  12. Thissen MR, Neumann MH, Schouten LJ: A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol 135 (10): 1177-83, 1999.

  13. Caccialanza M, Piccinno R, Moretti D, et al.: Radiotherapy of carcinomas of the skin overlying the cartilage of the nose: results in 405 lesions. Eur J Dermatol 13 (5): 462-5, 2003 Sep-Oct.

  14. Lovett RD, Perez CA, Shapiro SJ, et al.: External irradiation of epithelial skin cancer. Int J Radiat Oncol Biol Phys 19 (2): 235-42, 1990.

  15. Hall VL, Leppard BJ, McGill J, et al.: Treatment of basal-cell carcinoma: comparison of radiotherapy and cryotherapy. Clin Radiol 37 (1): 33-4, 1986.

  16. Silverman MK, Kopf AW, Grin CM, et al.: Recurrence rates of treated basal cell carcinomas. Part 2: Curettage-electrodesiccation. J Dermatol Surg Oncol 17 (9): 720-6, 1991.

  17. Wang I, Bendsoe N, Klinteberg CA, et al.: Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial. Br J Dermatol 144 (4): 832-40, 2001.

  18. Basset-Séguin N, Ibbotson S, Emtestam L, et al.: Photodynamic therapy using methyl aminolaevulinate is as efficacious as cryotherapy in basal cell carcinoma, with better cosmetic results. [Abstract] Br J Dermatol 149 (Suppl 64): A-P-66, 46, 2003.

  19. Basset-Séguin N, Ibbotson S, Emtestam L, et al.: Methyl aminolaevulinate photodynamic therapy vs. cryotherapy in primary superficial basal cell carcinoma: results of a 36-month follow-up. [Abstract] Br J Dermatol 153 (Suppl 1): A-P-30, 29. 2005.

  20. Hsi RA, Rosenthal DI, Glatstein E: Photodynamic therapy in the treatment of cancer: current state of the art. Drugs 57 (5): 725-34, 1999.

  21. Lui H, Hobbs L, Tope WD, et al.: Photodynamic therapy of multiple nonmelanoma skin cancers with verteporfin and red light-emitting diodes: two-year results evaluating tumor response and cosmetic outcomes. Arch Dermatol 140 (1): 26-32, 2004.

  22. Efudex® (fluorouracil) cream, 5% [package insert]. Aliso Viejo, Ca: Valeant Pharmaceuticals International, 2005. Available online. Last accessed October 25, 2013.

  23. Love WE, Bernhard JD, Bordeaux JS: Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review. Arch Dermatol 145 (12): 1431-8, 2009.

  24. Beutner KR, Geisse JK, Helman D, et al.: Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream. J Am Acad Dermatol 41 (6): 1002-7, 1999.

  25. Geisse JK, Rich P, Pandya A, et al.: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol 47 (3): 390-8, 2002.

  26. Geisse J, Caro I, Lindholm J, et al.: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol 50 (5): 722-33, 2004.

  27. Shumack S, Robinson J, Kossard S, et al.: Efficacy of topical 5% imiquimod cream for the treatment of nodular basal cell carcinoma: comparison of dosing regimens. Arch Dermatol 138 (9): 1165-71, 2002.

  28. Marks R, Gebauer K, Shumack S, et al.: Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicenter 6-week dose-response trial. J Am Acad Dermatol 44 (5): 807-13, 2001.

  29. Schulze HJ, Cribier B, Requena L, et al.: Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe. Br J Dermatol 152 (5): 939-47, 2005.

  30. Reszko A, Aasi SZ, Wilson LD, et al.: Cancer of the skin. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1610-33.

  31. Robinson JK: Risk of developing another basal cell carcinoma. A 5-year prospective study. Cancer 60 (1): 118-20, 1987.

  32. Karagas MR, Stukel TA, Greenberg ER, et al.: Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. Skin Cancer Prevention Study Group. JAMA 267 (24): 3305-10, 1992.

  33. Schinstine M, Goldman GD: Risk of synchronous and metachronous second nonmelanoma skin cancer when referred for Mohs micrographic surgery. J Am Acad Dermatol 44 (3): 497-9, 2001.

  34. Kiiski V, de Vries E, Flohil SC, et al.: Risk factors for single and multiple basal cell carcinomas. Arch Dermatol 146 (8): 848-55, 2010.

  35. Carneiro BA, Watkin WG, Mehta UK, et al.: Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia. Cancer Invest 24 (4): 396-400, 2006 Jun-Jul.

  36. Pfeiffer P, Hansen O, Rose C: Systemic cytotoxic therapy of basal cell carcinoma. A review of the literature. Eur J Cancer 26 (1): 73-7, 1990.

  37. Khandekar JD: Complete response of metastatic basal cell carcinoma to cisplatin chemotherapy: a report on two patients. Arch Dermatol 126 (12): 1660, 1990.

  38. Low JA, de Sauvage FJ: Clinical experience with Hedgehog pathway inhibitors. J Clin Oncol 28 (36): 5321-6, 2010.

  39. Von Hoff DD, LoRusso PM, Rudin CM, et al.: Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 361 (12): 1164-72, 2009.

  40. Skvara H, Kalthoff F, Meingassner JG, et al.: Topical treatment of Basal cell carcinomas in nevoid Basal cell carcinoma syndrome with a smoothened inhibitor. J Invest Dermatol 131 (8): 1735-44, 2011.

Squamous Cell Carcinoma of the Skin Treatment

Localized squamous cell carcinoma (SCC) of the skin is a highly curable disease.[1] There are a variety of treatment approaches to localized SCC, including excision, radiation therapy, cryosurgery, and electrodesiccation and curettage. Mohs micrographic surgery is a form of tumor excision that involves progressive radial sectioning and real-time examination of the resection margins until adequate uninvolved margins have been achieved, avoiding wider margins than needed.

There is little or no good-quality evidence that allows direct comparison of outcomes for patients with sporadic, clinically localized SCCs treated with local therapies. A systematic literature review found only one randomized controlled trial in the management of such patients, and that trial compared adjuvant therapy to observation after initial local therapy rather than different local therapies.[2] In that small single-center trial, 66 patients with high-risk, clinically localized SCC were assigned randomly, after surgical excision of the primary tumor (with or without radiation, depending on clinical judgment), to receive either combined 13-cis-retinoic acid (1 mg/kg orally per day) plus interferon-alpha (3 × 106 U subcutaneously 3 times/week) for 6 months or to observation.[3] In the 65 evaluable patients after a median follow-up of 21.5 months, there was no difference in the combined (primary) endpoint of SCC recurrence or second primary tumor (45% vs. 38%; hazard ratio = 1.13; 95% confidence interval [CI], 0.53–2.41), nor in either of the individual components of the primary endpoint.[3][Level of evidence 1iiDii]

Absent high-quality evidence from controlled clinical trials, the management of clinically localized cutaneous SCC is based upon case series and consensus statements from experts.[4] The commonly used treatments are listed below.

Treatment for Squamous Cell Carcinoma of the Skin

Treatment options include the following:

  1. Surgical excision with margin evaluation.
  2. Mohs micrographic surgery.
  3. Radiation therapy.
  4. Curettage and electrodesiccation.
  5. Cryosurgery.

Surgical excision with margin evaluation

Excision is probably the most common therapy for SCC.[4] This traditional surgical treatment usually relies on surgical margins ranging from 4 mm to 10 mm, depending on the diameter of the tumor and degree of differentiation. In a prospective case series of 141 SCCs, a 4-mm margin was adequate to encompass all subclinical microscopic tumor extension in more than 95% of well-differentiated tumors up to 19 mm in diameter. Wider margins of 6 mm to 10 mm were needed for larger or less-differentiated tumors or tumors in high-risk locations (e.g., scalp, ears, eyelids, nose, and lips).[5] Re-excision may be required if the surgical margin is found to be inadequate on permanent sectioning.

Mohs micrographic surgery

Mohs micrographic surgery is a specialized technique used to achieve the narrowest margins necessary to avoid tumor recurrence, while maximally preserving cosmesis. In case series, it has been associated with a lower local recurrence rate than the other local modalities,[6] but there are no randomized trials allowing direct comparison.[2] This surgery is best suited to the management of tumors in cosmetically sensitive areas or for tumors that have recurred after initial excision (e.g., eyelid periorbital area, nasolabial fold, nose-cheek angle, posterior cheek sulcus, pinna, ear canal, forehead, scalp, fingers, and genitalia).[7][8]

Mohs micrographic surgery is also often used to treat high-risk tumors with poorly defined clinical borders or with perineural invasion. The method requires special training. The tumor is microscopically delineated, with serial radial resection, until it is completely removed as assessed with real-time frozen sections. Nevertheless, since the technique removes tumor growing in contiguity and may miss noncontiguous in-transit cutaneous micrometastases, some practitioners remove an additional margin of skin in high-risk lesions even after the Mohs surgical procedure confirms uninvolved margins.[4][Level of evidence: 3iiiDiv]

Radiation therapy

Radiation therapy is a logical treatment choice, particularly for patients with primary lesions requiring difficult or extensive surgery (e.g., nose, lip, or ears).[4][9] Radiation therapy eliminates the need for skin grafting when surgery would result in an extensive defect. Cosmetic results are generally good, with a small amount of hypopigmentation or telangiectasia in the treatment port. Radiation therapy can also be used for lesions that recur after a primary surgical approach.[10] Radiation therapy is avoided in patients with conditions that predispose them to radiation-induced cancers, such as xeroderma pigmentosum or basal cell nevus syndrome.

Although radiation therapy, with or without excision of the primary tumor, is used for histologically proven clinical lymph node metastases and has been associated with favorable disease-free survival rates, the retrospective nature of these case series makes it difficult to know the impact of nodal radiation on survival.[11][12][Level of evidence 3iiiDii]

Curettage and electrodesiccation

This procedure is also sometimes called electrosurgery. A sharp curette is used to scrape the tumor down to its base, followed by electrodesiccation of the lesion base. Although it is a quick method for destroying the tumor, the adequacy of treatment cannot be assessed immediately since the surgeon cannot visually detect the depth of microscopic tumor invasion. Its use is limited to small (<1 cm), well-defined, and well-differentiated tumors.[4][Level of evidence: 3iiiDii]

Cryosurgery

Cryosurgery may be considered for patients with small, clinically well-defined primary tumors. It may be useful for patients with medical conditions that preclude other types of surgery. Contraindications include abnormal cold tolerance, cryoglobulinemia, cryofibrinogenemia, Raynaud disease (in the case of lesions on hands and feet), and platelet deficiency disorders. Additional contraindications to cryosurgery include tumors of the scalp, ala nasi, nasolabial fold, tragus, postauricular sulcus, free eyelid margin, upper lip vermillion border, lower legs, and tumors near nerves. Caution should also be used before treating nodular ulcerative neoplasia more than 3 cm in diameter, carcinomas fixed to the underlying bone or cartilage, tumors situated on the lateral margins of the fingers and at the ulnar fossa of the elbow, or recurrent carcinomas following surgical excision.

Edema is common following treatment, especially around the periorbital region, temple, and forehead. Treated tumors usually exude necrotic material after which an eschar forms and persists for about 4 weeks. Permanent pigment loss at the treatment site is unavoidable, so the treatment is not well suited to dark-skinned patients. Atrophy and hypertrophic scarring have been reported as well as instances of motor and sensory neuropathy.

The management of SCC in situ (Bowen disease) is similar to good-risk SCC. However, since it is noninvasive, surgical excision, including Mohs micrographic surgery, is usually not necessary. In addition, high complete response (CR) rates are achievable with photodynamic therapy (PDT). In a multicenter trial, 229 patients (209 evaluated in the per-protocol/per-lesion analysis) were randomly assigned to receive PDT (methyl aminolevulinate + 570–670 nm red light; n = 91), placebo cream with red light (n = 15); or treatment by physician choice (cryotherapy, n = 77; topical 5-fluorouracil, n = 26).[13] The sustained complete clinical response rates at 12 months were 80%, 67%, and 69% in the three respective active therapy groups (P = .04 for the comparison between PDT and the two combined physician-choice groups).[13][Level of evidence 1iiDii] The cosmetic results were best in the PDT group. (For comparison, the CR rates at 3 months for PDT and placebo/PDT were 93% and 21%, respectively.)

Treatment for Recurrent Squamous Cell Carcinoma of the Skin

SCCs have definite metastatic potential, and patients should be followed regularly after initial treatment. Overall, local recurrence rates after treatment of primary SCCs ranged from about 3% to 23%, depending upon anatomic site.[6] About 58% of local recurrences manifest within 1 year, 83% within 3 years, and 95% within 5 years. The metastatic rate for primary tumors of sun-exposed skin is 5%; for tumors of the external ear, 9%; and for tumors of the lip, 14%. Metastases occur at an even higher rate for primary SCCs in scar carcinomas or in nonexposed areas of skin (about 38%).[6] About 69% of metastases are diagnosed within 1 year, 91% within 3 years, and 96% within 5 years. Tumors that are 2 cm or larger in diameter, 4 mm or greater in depth, or poorly differentiated have a relatively bad prognosis [14] and even higher local recurrence and metastasis rates than those listed.[6] Reported rates also vary by treatment modality, with the lowest rates associated with Mohs micrographic surgery, but at least some of the variation may be the result of patient selection factors; no randomized trials directly compare the various local treatment modalities.

Recurrent nonmetastatic SCCs are considered high risk and are generally treated with excision, often using Mohs micrographic surgery. Radiation therapy is used for lesions that cannot be completely resected.

As is the case with BCC, patients who develop a primary SCC are also at increased risk of subsequent primary skin cancers because the susceptibility of their sun-damaged skin to additional cancers persists.[15][16]

Treatment for Metastatic Squamous Cell Carcinoma (or Advanced Disease Untreatable by Local Modalities)

As is the case with BCC, metastatic and far-advanced SCC is unusual, and reports of systemic therapy are limited to case reports and very small case series with tumor response as the endpoint.[Level of evidence 3iiiDiv] Cisplatin-based regimens appear to be associated with high initial tumor response rates.[17][18] High response rates have also been reported with the use of 13-cis-retinoic acid plus interferon-alpha-2a.[19] Since there is no standard therapy, clinical trials are appropriate if available. Information about ongoing clinical trials is available from the NCI Web site.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with squamous cell carcinoma of the skin. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Preston DS, Stern RS: Nonmelanoma cancers of the skin. N Engl J Med 327 (23): 1649-62, 1992.

  2. Lansbury L, Leonardi-Bee J, Perkins W, et al.: Interventions for non-metastatic squamous cell carcinoma of the skin. Cochrane Database Syst Rev (4): CD007869, 2010.

  3. Brewster AM, Lee JJ, Clayman GL, et al.: Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma. J Clin Oncol 25 (15): 1974-8, 2007.

  4. Motley R, Kersey P, Lawrence C, et al.: Multiprofessional guidelines for the management of the patient with primary cutaneous squamous cell carcinoma. Br J Dermatol 146 (1): 18-25, 2002.

  5. Brodland DG, Zitelli JA: Surgical margins for excision of primary cutaneous squamous cell carcinoma. J Am Acad Dermatol 27 (2 Pt 1): 241-8, 1992.

  6. Rowe DE, Carroll RJ, Day CL Jr: Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol 26 (6): 976-90, 1992.

  7. Thomas RM, Amonette RA: Mohs micrographic surgery. Am Fam Physician 37 (3): 135-42, 1988.

  8. Rowe DE, Carroll RJ, Day CL Jr: Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 15 (4): 424-31, 1989.

  9. Caccialanza M, Piccinno R, Moretti D, et al.: Radiotherapy of carcinomas of the skin overlying the cartilage of the nose: results in 405 lesions. Eur J Dermatol 13 (5): 462-5, 2003 Sep-Oct.

  10. Lovett RD, Perez CA, Shapiro SJ, et al.: External irradiation of epithelial skin cancer. Int J Radiat Oncol Biol Phys 19 (2): 235-42, 1990.

  11. Shimm DS, Wilder RB: Radiation therapy for squamous cell carcinoma of the skin. Am J Clin Oncol 14 (5): 383-6, 1991.

  12. Veness MJ, Palme CE, Smith M, et al.: Cutaneous head and neck squamous cell carcinoma metastatic to cervical lymph nodes (nonparotid): a better outcome with surgery and adjuvant radiotherapy. Laryngoscope 113 (10): 1827-33, 2003.

  13. Morton C, Horn M, Leman J, et al.: Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial. Arch Dermatol 142 (6): 729-35, 2006.

  14. Cherpelis BS, Marcusen C, Lang PG: Prognostic factors for metastasis in squamous cell carcinoma of the skin. Dermatol Surg 28 (3): 268-73, 2002.

  15. Karagas MR, Stukel TA, Greenberg ER, et al.: Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. Skin Cancer Prevention Study Group. JAMA 267 (24): 3305-10, 1992.

  16. Schinstine M, Goldman GD: Risk of synchronous and metachronous second nonmelanoma skin cancer when referred for Mohs micrographic surgery. J Am Acad Dermatol 44 (3): 497-9, 2001.

  17. Luxenberg MN, Guthrie TH Jr: Chemotherapy of basal cell and squamous cell carcinoma of the eyelids and periorbital tissues. Ophthalmology 93 (4): 504-10, 1986.

  18. Sadek H, Azli N, Wendling JL, et al.: Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin. Cancer 66 (8): 1692-6, 1990.

  19. Lippman SM, Parkinson DR, Itri LM, et al.: 13-cis-retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst 84 (4): 235-41, 1992.

Treatment of Actinic Keratosis

Actinic keratoses commonly appear in areas of chronic sun exposure, such as the face and dorsa of the hands. Actinic cheilitis is a related condition that usually appears on the lower lips.[1] These conditions represent early epithelial transformation that may eventually evolve into invasive SCC.

Actinic keratosis is a noninvasive lesion. The progression rate is extremely low. In a prospective study, the progression rate to SCC was less than 1 in 1,000 per year, calling into question the cost effectiveness of treating all actinic keratoses to prevent SCC.[2] Moreover, in a population-based longitudinal study, there was an approximately 26% spontaneous regression rate of solar keratoses within 1 year of a screening examination.[3] Therefore, studies designed to test the efficacy of any treatment for progression of actinic keratoses to SCC are impractical (or impossible). Nevertheless, a variety of treatment approaches have been reviewed.[4]

Treatment for Actinic Keratosis

Treatment options include the following:

  1. Topical agents:
    • Fluorouracil (5-FU).
    • Imiquimod cream.
    • Diclofenac sodium 3% gel.
    • Trichloroacetic acid.
  2. Cryosurgery.
  3. Curettage.
  4. Dermabrasion.
  5. Shave excision.
  6. Photodynamic therapy.
  7. Carbon dioxide laser.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with actinic keratosis. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Picascia DD, Robinson JK: Actinic cheilitis: a review of the etiology, differential diagnosis, and treatment. J Am Acad Dermatol 17 (2 Pt 1): 255-64, 1987.

  2. Marks R, Rennie G, Selwood TS: Malignant transformation of solar keratoses to squamous cell carcinoma. Lancet 1 (8589): 795-7, 1988.

  3. Marks R, Foley P, Goodman G, et al.: Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol 115 (6): 649-55, 1986.

  4. Jorizzo J, Collier A: Actinic keratosis. Waltham, Ma: UpToDate Inc, 2011. Available online. Last accessed October 25, 2013.


This information is provided by the National Cancer Institute.

This information was last updated on October 25, 2013.

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