Once you have gone over the pathology report and staging information with your doctor, it’s time to plan the treatment strategy. In this section, we discuss the different types of therapy that are available for basal cell carcinoma (BCC) and their advantages and disadvantages.
No treatment
As basal cell carcinomas are not life-threatening and slow-growing, it can be reasonable to not have any treatment if they are not bothering the patient. Examples where no treatment (or monitoring the lesion) may be appropriate include patients with another life-limiting illness (e.g. end-stage heart failure, metastatic cancer) or much older patients (e.g. over the age of 90).
Surface/Destructive Therapy
These are treatments that are applied directly to your skin to treat BCC.
Curettage & Cautery (C&C)
In this procedure, the doctor scrapes the cancer from your skin (curettage). Then s/he applies heat to destroy any remaining cancer cells (electrodessication), which also stops any bleeding.
Advantages:
- It’s quick, often completed in one office visit
- It does not require stitches (or a follow-up appointment to remove them)
- It’s a non-invasive option for people who don’t want or can’t tolerate a more-invasive procedure
- For high-risk groups who may have numerous BCCs, C & C allows rapid treatment of multiple cancers at the same time. It’s just important to check the pathology to make sure there are no high-risk features
Disadvantages:
- It is not as effective as surgery
- It does not work well on areas that have hair
- It may not heal as well as an excision, so it probably should not be used on an area where you are concerned about the appearance
- If the tumour is deeper than they expected, it may still need to be surgically removed
Cryosurgery
This procedure involves applying a cold substance, such as liquid nitrogen, to the tumour and freezing it off. It may be considered for low-risk BCC when more effective therapies are either not advised or impractical. It can also be considered in individuals with conditions that cause them to form large numbers of tumours.
Topical Medication Treatments
Two medications are used in low-risk BCCs or when a patient has a large number of small BCCs within a region. Topical medications are most appropriate for basal cell carcinomas which are ‘superficial’ when examined under a microscope.
Imiquimod (Aldara®)
This drug modulates the immune system and has been approved by the US Food and Drug Administration (FDA) for treatment of superficial BCC on the trunk, neck, and extremities. It is usually applied five times per week for a minimum of six weeks.
5-Fluorouracil (5-FU)
This is a chemotherapeutic medication that is usually applied twice daily for three to six weeks.
Both imiquimod and 5-FU act to destroy cancer cells, so you will most likely feel effects where they have been applied. These include skin redness, swelling, sores, crusting, itching, and tingling.
Surgery
Surgical removal is the gold standard of treatment for basal cell carcinoma. There are two general types of surgery for BCC:
Wide Local Excision
A dermatologist (or specialised surgeon) cuts out the cancer and an area around the tumour. Removing an extra part of skin (a wide margin) assures that s/he got all the cancer. If there is a big enough margin of normal skin around the cancer cells, your treatment is complete. If not, your doctor may need to go back and take more.
Mohs Micrographic Surgery (MMS)
Mohs (rhymes with nose) micrographic surgery is recommended for BCC that is likely to recur (come back) or is in an area where you don’t want to remove a lot of skin (such as the face, neck, or hand). Mohs surgery is not appropriate for all BCC, and your BCC must meet certain criteria, such as size or location on the central face, for Mohs surgery to be considered appropriate according to UK guidelines. Mohs surgery has the highest cure rate, whilst preserving the maximum amount of healthy skin (i.e. smallest scar of any surgical treatment).
Mohs surgery is named after Dr Frederic Mohs, who pioneered the technique.
In Mohs (also called microscopic controlled excision) surgery, you are awake while the surgeon removes the smallest amount of tissue needed to treat the cancer. This procedure is normally done as an outpatient. It is done at a hospital only rarely, when surgery will be extensive.
The surgeon removes the skin cancer that can be seen. Then a thin layer of surrounding skin is cut away and examined under a microscope. If cancer cells are found in that additional layer, the process will be repeated until no cancer cells can be seen. The Mohs surgeon will then discuss with you the best way to treat (‘reconstruct’) the resultant wound, which will normally be that same day. Occasionally, after the tumour has been removed, a dressing is placed on the wound and the wound repaired by a different team (e.g. oculoplastic surgeon, maxillofacial surgeon) the next day. Your Mohs surgeon will discuss this with you before the date of the surgery.
Radiation Therapy
Radiation therapy is used if you can’t receive surgery or if you really don’t want it. Or in some cases, radiation is given for people who have aggressive BCC as a follow-up treatment to surgery to help destroy any remaining cancer cells so that the cancer does not come back (adjuvant therapy). The radiation therapy is given at a hospital or treatment centre over a period of several weeks. Radiation is typically only used in people 60 years of age or older.
Light (Photodynamic) Therapy
This treatment uses light-activated radiotherapy. It’s a two-part process: A solution (called a photosensitizer) that makes your skin sensitive to light is applied to the cancer and a portion of surrounding skin. After one or more hours, a coloured or white light will be aimed at the BCC to kill the cancer cells. You may need a single treatment or multiple treatments.
This method works well for small, well-defined superficial BCCs. Potential side effects include being sensitive to the sun (requiring you to avoid the sun and use photoprotection for 48 hours) as well as redness, swelling, tenderness, and sometimes crusting or erosions.
Laser treatments are not recommended for treatment of BCC.
Adjuvant therapy: Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. For squamous cell skin cancer, the primary treatment is usually surgery. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, biological therapy, or immunotherapy.
Systemic Therapy
Oral Medications
Two medications that are taken in a pill form approved by the FDA and are available for advanced BCC. Both of these drugs belong in a class of drugs called hedgehog inhibitors. These drugs are:
Vismodegib (Erivedge®) (vis-moe-deh-gib) is an inhibitor of smoothened (SMO) protein, part of the Hedgehog pathway. This therapy was approved by the FDA in 2012 for advanced BCC, including both locally advanced and metastatic disease.
Sonidegib (Odomzo®) (so-nī-deh-gib) is a prescription medication used to treat adults with locally advanced BCC that has come back following surgery or radiation or that cannot be treated with surgery or radiation. This drug was approved by the FDA in 2015. Sonidegib is not FDA approved for metastatic BCC.
Vismodegib and sonidegib stop or slow down the spread of the cancer and shrink the tumours in some patients. In fact, some patients with locally advanced BCC even see their tumours disappear. These drugs are generally taken as long as they are working and the side effects are tolerable.
Hedgehog inhibitors have a number of side effects, including muscle spasms, weight loss, altered taste, fatigue, hair loss, nausea (being sick to stomach), and diarrhoea (loose stools). In addition, there may also be some liver problems associated with these agents. The most critical side effect is foetal harm—When a baby is exposed to these drugs in utero, the drugs can cause the baby to die before it is born or cause severe birth defects. Therefore, both women with reproductive potential and men whose partners have reproductive potential should practice birth control while taking these medications if they are sexually active to avoid pregnancy and potential foetal harm.
The side effects of hedgehog inhibitors led to about 28% of subjects discontinuing therapy in these clinical trials, so the tolerability issue is a factor to consider. Be sure to have a conversation with your provider about the potential side effects prior to starting therapy. It helps if you know what to expect and there is a plan in place to communicate and manage these side effects proactively. See the Effects of hedgehog Inhibitors in the LIVING WITH BASAL CELL CARCINOMA section for more strategies to address potential side effects.
Intravenous Medication
Cemiplimab (Libtayo®) LIBTAYO as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic basal cell carcinoma (laBCC or mBCC) who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI). Cemiplimab belongs to a class of drugs called programmed cell death protein 1 (PD-1) inhibitors. PD-1 inhibitors reactivate part of the immune system (the T-cell system) that has been suppressed by cancer cells. When this T-cell system is reactivated, it can then do its job and seek out and kill cancer cells.
In clinical trials, in patients with locally advanced BCC, cemiplimab shrank tumours in 23% while 6% had tumours that disappeared completely. The response lasted 6 months or longer in 79% of the these patients who responded to cemiplimab. For patients with metastatic BCC (meaning it had spread to the lymph nodes or distant regions) cemiplimab shrank tumours in 21% of patients, and all of those patients had responses that lasted at least 6 months.
In these studies, the most common side effects associated with cemiplimab were tiredness, musculoskeletal pain, diarrhoea, rash, itching, and upper respiratory infection. Cemiplimab can cause side effects that are typically seen with PD-1 inhibitors, which are mostly related to the immune system being activated. These side effects included lung problems, intestinal problems, liver problems, hormonal issues, kidney problems, and skin issues such as rash, blistering, and sores in the mouth.
Investigational Agents
A number of trials are ongoing with multiple investigational agents and approaches for BCC. Some involve use of various hedgehog inhibitors to prevent BCC from coming back or to treat the tumour before surgery to make it more manageable during and after surgery (neoadjuvant therapy). Additional studies of immuno-oncology therapies are ongoing for BCC; other studies are examining various therapy combinations to treat BCC.
Neoadjuvant describes a therapy given as a first step to shrink a tumour before the main therapy, which is usually surgery. In patients with BCC, a pathway involved with cellular signalling, the hedgehog pathway, is overactive, leading to unrestricted cellular proliferation/development of cancer. Some patients with genetic disorders leading to BCC have mutations in genes such as PTCH, which normally restricts the hedgehog pathway. That’s why patients with some genetic disorders develop so many BCCs–they don’t have a way to suppress that pathway. Hedgehog inhibitors slow down this overactive hedgehog pathway, thereby slowing or stopping the growth of BCCs.
But where does the term hedgehog come from? Turns out the hedgehog pathway is also involved with embryonic development. The name is used because one of the intercellular molecules involved in the pathway, a molecule called Hedgehog (Hg), is found in fruit flies. When fruit flies lack (or have a mutation in) the Hg gene, their larvae are affected. The larvae take on a different shape and are said to resemble hedgehogs, as shown below.
This fact is relevant. In humans, hedgehog inhibitors also have an effect on foetal development, which explains why both vismodegib and sonidegib carry a strong warning—called a Black Box warning in pharmaceutical lingo—about potential foetal harm.
Clinical trials are research studies that test how well new medical approaches work. They have an important place in your care as researchers strive to improve current cancer treatments and search for new and better ones. Clinical trials are essential for learning about cancer and how to prevent or cure it.
Our most-effective cancer treatments would not be available without the clinical trial process. Unfortunately, many people with cancer are unaware of the option for a clinical trial or are unsure about the value of participation.
Your goal is to find the best treatment available whenever you make a treatment decision. While there may be a good standard of care for you—care that experts believe is appropriate for your specific diagnosis and treatment history—sometimes the current standard of care is not as effective as you and your doctor would like. Other times, the standard of care works for a time but then stops working. In still other instances, there is no standard of care for your situation. At these times, participation in a clinical trial may be the best option for you.
The best time to search for clinical trials is every time you are faced with a treatment decision.