The goals of treating squamous cell skin cancer (SCSC) are to remove the tumor, preserve function, and prevent skin damage. Most people diagnosed with SCSC can be cured by surgically excising or removing the tumor(s). Without treatment, further skin damage and life-threatening cancer can develop.

Below are descriptions of approved and available treatments for SCSC. It is important to note that not all of the treatment options described will apply to every situation. Your healthcare providers will determine which treatments apply to your SCSC.

Curettage & Electrodesiccation

For curettage and electrodesiccation, the clinician scrapes the cancer from the skin with a sharp, looped tool called a curette, then immediately cauterizes the site. Electrodessication, the second step, prevents bleeding at the site without using sutures and burns off residual cancer cells. The wounded site will then be covered with gauze and heals with time. This procedure is a technique effective for low-risk SCSC. Areas with hair growth are unsuitable for this technique due to the potential for inadequate tumor removal and the subsequent risk of spreading.

Shave Excision or Standard Surgical Excision

With these techniques, the clinician removes the suspicious skin lesion. The difference between the names includes the amount of tissue removed, whether stitches are necessary for the wound, and whether a noticeable scar will develop. The techniques have other minor differences in the tools used.
A shave excision is superficial or closer to the skin’s surface and usually applies to tiny, low-risk lesions. A standard surgical excision removes more tissue, may need stitching, and produces a noticeable scar.

Standard excision is recommended as the primary treatment for low-risk SCSCs. It is recommended for high-risk if Mohs micrographic surgery is unavailable.

For excision, the epidermal or dermal lesion is removed by slicing the skin. Excision is a quick procedure that can be performed in an office setting. The area is numbed with local anesthesia before removing the lesion with a scalpel or electrosurgical loop. The bleeding is immediately stopped with a special solution applied topically at the site or stitches before placing a bandage over the wound.

For low-risk SCSC less than two cm in diameter, the lesion should be removed with four mm of tissue surrounding the tumor. If the low-risk lesion is greater than two cm, then six mm of tissue surrounding the tumor is needed to remove cancer cells with some normal cells.

After removing the tissue, the sample is sent to a laboratory for examination, where it will be assessed to make sure all the cancer has been removed along the margins of the tumor. On your pathology report, the terms negative, clean, not involved, or clear margins indicate that the tumor is surrounded by normal tissue and has been adequately removed. If the areas around the tumor do not show healthy cells, you may need to have further excision during another appointment to obtain clear margins. Other techniques may be recommended if positive margins are observed.

Even with clear margins, you may be recommended for routine follow-up care after this outcome. In some cases, reconstruction, tissue repair, or skin grafting are undertaken after clear margins are achieved. Standard excision with margin assessment has a better cure rate versus curettage and electrodesiccation.

Mohs Micrographic Surgery

Mohs surgery is the preferred treatment option for people with SCSC because it allows clinicians to achieve a complete removal of all cancer cells observed. For SCSCs confined to the skin, outcomes of Mohs surgery show significantly fewer cancer recurrences compared to standard excision. Mohs improves the outcomes of removing all of the tumor cells present because the process requires a continuous reexamination of the tissue. Although it is a superior technique, it requires a certified specialist, and it is not appropriate in all cases.

Mohs surgery involves removing thin layers of skin one layer at a time and examining each layer under a microscope to determine if any cancer remains. Mohs incorporates a process by which the surgically removed tissue is carefully mapped, color-coded, and microscopically examined. Mapping allows the surgeon to pinpoint the location of the cells on the image back to the skin site. The mapped tissue edges and undersurface are then examined under a microscope to determine whether these areas contain normal or cancer cells. If cancer cells appear, the map specifies the region requiring additional tissue removal. Future excision will come from only that site, sparing healthy tissue that might otherwise be removed. Another layer is taken from the site with the cancer cells, and the process is repeated. Mohs surgery is complete once the tissue edges and undersurface are absent of cancer cells.

Radiation Therapy

Radiation involves concentrating a beam of energy on the tumor. The intense radiation will cause massive damage inside the cancer cells, which will lead to their death. This type of therapy is administered by a radiation specialist at a hospital or treatment center and may last six or more weeks.

Radiation therapy schedules vary among patients, and treatment could occur daily or two to four treatments per week, depending on each case.

Surgery or excision is preferred for removing SCSC on the skin, but radiation can be used as a primary treatment for SCSC. Caution is warranted when using this treatment because it increases the risk of developing secondary skin cancer within the radiation field. Poor cosmetic consequences may also result, like skin pig mentation changes, widening of blood vessels, non-healing ulcers, tissue death, and scarring. Radiation therapy is not appropriate for individuals who inherited genetic conditions that predispose them to skin cancer because the radiation may cause cancer.

If positive margins with tumor cells are detected following surgery, radiation therapy may be recommended as “adjuvant” therapy (meaning an additional or supplement) because it improves the outcome of treatment. Radiation therapy may be used for patients who cannot undergo surgery or who have residual disease where additional surgery is not feasible. A radiation oncologist will determine appropriate options for radiation therapy in each case.

Several variations in radiation therapy are available. Various external beam options effectively treat SCSC and have similar cosmetic and safety results. Protracted fractionation or giving lower doses and spreading these out over time can be used for poorly vascularized or cartilaginous areas. The unique dosing and timing improve cosmetic results with protracted fractionation. Brachytherapy, using implanted isotope-based radiation, can be effective for SCSC on the head and neck. However, insufficient long-term efficacy and safety data to support the routine use of electronic surface brachytherapy.

Precancer Treatments Applied to the Skin

In patients with SCSC precancers, called actinic keratoses, there are many options for topical therapy. These include the options below. Oral, but not topical, retinoids may also be effective in reducing SCSCs and actinic keratoses in some patients, although these medications have side effects.

5-fluorouracil is a traditional chemotherapy but is supplied in more than one formulation, depending on the type of cancer for which it is needed. For skin cancer, it can be applied as a topical cream directly to the skin twice daily to destroy actinic keratoses. Topical 5-fluorouracil is a non-invasive and non-disfiguring method of killing the skin cancer cells. The topical solution is absorbed by the cancer cells, which mistake 5-fluorouracil for a metabolite they require to assemble DNA. The cancer cells cannot use 5-fluorouracil to make DNA and will die due to missing this critical component.

5-fluorouracil/calcipotriol (calcipotriene) is a topical ointment mixture of 5-fluorouracil cream and calcipotriene. Calcipotriol is a derivative of vitamin D and is reported to enhance the immune system. Compared to 5-fluorouracil cream, the mixture reduces the duration of treatment time to days from weeks and improves efficacy. A small number of patients reported burning, stinging, tingling, and rash with calcipotriene. Overall, the combination ointment reduces irritation and inflammation compared to the fluorouracil cream without calcipotriol.

Imiquimod is a drug that activates and amplifies the immune system. It is prescribed as a topical cream for actinic keratoses. By generating an immune system reaction at skin sites where it is applied externally, imiquimod results in the death of precancerous cells. Application may be several times weekly for up to six weeks, depending on the case. Some applications of imiquimod may last longer. The skin may react with a rash, burning, or pain at the application site.

Tirbanibulin is a topical solution to treat actinic keratosis on the face and scalp. The goal is to prevent these lesions from developing into invasive SCSC. Tirbanibulin is applied once daily for five consecutive days. It prevents the cancer cells from dividing into more cells and they will eventually die. Some people will experience mild flaking, rash, or pain at the application site.

Diclofenac is a non-steroidal anti-inflammatory agent that has been long-established and used to reduce pain and inflammation. It is applied as an ointment twice a day for 60-90 days for the topical treatment of actinic keratoses. Some patients will experience skin irritation at the site of application. The way this drug works has yet to be completely understood but is likely due to its ability to reduce inflammatory processes in cells.

Chemical peel with trichloroacetic acid may be appropriate for people with extensive actinic keratoses on their face and scalp. This treatment should be performed by a professional and will cause the top layer of skin to come off. The clinician may give you a sedative and mild pain medication before applying trichloroacetic acid to the area. The peel’s effects will cause irritation and redness on the facial skin for up to a month. After wound healing, some patients report improved cosmetic results in addition to lesion removal.

Photodynamic therapy combines medicine with light to kill the tumor cells. In the first part of this technique, a medication that will later sensitize the cancer cells to light is prescribed. Examples of this medicine include 5-aminolevulinic acid and porfimer sodium. It takes a day or two for the cancer cells to absorb the light-sensitizing medicine. Then, a light with a specific wavelength of energy is focused at the SCSC. This process creates toxic free oxygen radicals inside the cancer cells, which kills them. Superficial tumors (those that are small and/or not deep) are ideal for this therapy. Light cannot completely penetrate deep or large tumors.

Medications for Regional and Metastatic Squamous Cell Skin Cancer

The two most commonly given treatments that are approved and available for regional and metastatic SCSC are cemiplimab (Libtayo) and pembrolizumab (Keytruda). Both are systemic therapies (those that spread throughout the body to treat cancer) and may be combined with other types of therapy. Your regimen will be recommended depending on your type of cancer.

Cemiplimab (Libtayo) is an intravenous medication indicated for the treatment of patients with SCSC that has spread regionally or metastatic SCSC who are not candidates for curative surgery or curative radiation. Cemiplimab is a drug designed to generate an immune system reaction to the tumor cells. This drug is also approved for basal cell carcinoma and some non-small cell lung cancers. Cemiplimab is given in a clinic or hospital as an intravenous infusion over 30 minutes. It can be used every three weeks for up to two years. If this medication is taken alone, the most common adverse reactions include rash, itching, diarrhea, fatigue, muscle/joint pain, and/or gland dysfunction. Warnings that accompany this medication include the possibility of severe, potentially life threatening inflammatory reactions, a reaction during the infusion, and embryo toxicity. Cemiplimab cannot be used while pregnant or lactating, and all measures to prevent pregnancy must be strictly followed.

Pembrolizumab (Keytruda) is an intravenous medication approved for the treatment of patients with recurrent or metastatic SCSC or locally advanced SCSC that is not curable by surgery or radiation. It is administered by health care staff at a clinic or hospital at a dose of 200 mg every three weeks or 400 mg every six weeks for up to two years. This drug is given to patients with many other cancers. Pembrolizumab works by reenergizing your immune system, allowing it to recognize the harm cancer cells are doing in your body, activate other immune cells, and fight back to eliminate the tumor. The side effects of this drug are usually similar to mild allergic reactions and inflammation because of the immune system stimulation and may include skin rash, intestinal issues, organ problems, and reactions on infusion. Usually, these are mild but could result in the discontinuation of the drug.

Clinical Trials

Depending on your SCSC type, a clinical trial may open for enrollment and appropriate to consider. Clinical trials are experimental research studies that test a new approach or therapy under the guidance of clinicians and a medical review board. These trials are entirely optional for patients. If current and approved treatments are not effectively treating your cancer, clinical trial options may be worthwhile to investigate.