Advanced Basal Cell Carcinoma

Anti-Tumour Treatment: “Emerging trends in the treatment of advanced basal cell carcinoma.”

What Is Advanced Basal Cell Carcinoma?

Advanced basal cell carcinoma is a more complex type of basal cell carcinoma (BCC) — the most common kind of skin cancer. You usually get it from lots of unprotected sun exposure. But environmental and lifestyle factors, certain medication, and your genes can play a role.

A doctor can help you find the best treatment. You might need radiation, surgery, or special drugs. But you’ll need to get care right away. That’s because this kind of skin cancer can damage your tissue or bones. And it can be life-threatening if left untreated.

What Makes It Advanced?

Experts don’t agree on one definition. But it’s generally considered BCC that’s hard to treat with standard therapy.

Problems come up for a number of reasons. For example, your tumor might be more aggressive. That means it grows faster and is deeper than typical BCC. Or maybe surgery isn’t possible because the tumor is too close to a vital organ, like your brain.

Other factors that lead to a diagnosis of advanced BCC include:

  • Your tumor covers a big area
  • Edges of your tumor aren’t well-defined
  • Radiation therapy isn’t possible
  • Your previous treatment didn’t work
  • Your cancer grows fast or comes back

There are two categories:

Locally advanced BCC. This is when the cancer spreads to tissue around your original tumor. It’s what happens most of the time with advanced BCC.

Metastatic BCC. Very rarely, BCC can spread to different parts of your body. That means cells from your original tumor show up somewhere else. Your doctor is most likely to find metastatic BCC in your bones, lungs, liver, or lymph nodes. This is the most serious kind of advanced BCC.

How Is It Different From Other Skin Cancer?

Advanced BCC starts in your basal cells, which are in the top layer of your skin. It also tends to grow a lot slower than melanoma. That’s the deadliest kind of skin cancer. It starts in cells called melanocytes.

Where Can You Get It?

Any kind of skin cancer is more likely to show up on areas exposed to the sun. Most of the time, advanced BCC affects you from the neck up. But it’s possible to get it other places, like your genitals.

Advanced BCC more commonly affects these areas:

  • Eye or eyelid
  • Brain
  • Ear canal
  • Nose
  • Lips
  • Bones in your face or skull

It sometimes leads to complications such as:

  • Unwanted cosmetic changes
  • Trouble hearing or seeing
  • Nerve problems in your head or neck
  • Central nervous system issues

Who Gets It?

It’s hard to predict who’ll get advanced BCC. Some things that raise your chances include:

  • A history of skin cancer
  • Certain genetic disorders
  • Not getting early medical care
  • Taking long-term medicine to slow down your immune system

How Do You Treat It?

Your health care team will come up with a plan based on your specific case.

  • Surgery
  • Radiation
  • Chemotherapy
  • Targeted therapy

There’s ongoing research into what works best for advanced BCC. Your doctor might suggest joining a clinical trial if other treatments aren’t successful. That’s a study that looks at new kinds of drugs or treatment methods.

When to See Your Doctor

Skin cancer is more likely to show up in certain people, like those with fair skin. But anyone can get it. You should check with your regular doctor or a dermatologist whenever you see certain changes in your skin.

Here are some signs to watch for:

  • A sore that won’t heal
  • A shiny bump
  • A new brown spot (in people with darker skin)
  • A bump with a dent or rolled edges
  • A growth that itches, bleeds, leaks pus, or gets crusty

Show Sources

SOURCES:

Current Dermatology Reports: “Advanced Basal Cell Carcinoma: Epidemiology and Therapeutic Innovations.”

Frontiers in Oncology: “Sonidegib for the Treatment of Advanced Basal Cell Carcinoma.”

McDaniel, B., Badri, T., Steele, R.B. Basal Cell Carcinoma. StatPearls, 2020.

Clinical & Translational Oncology: “Management of high-risk and advanced basal cell carcinoma.”

Dermatology and Therapy: “Sonidegib: Safety and Efficacy in Treatment of Advanced Basal Cell Carcinoma.”

Cancer Support Community: “Advanced Basal Cell Carcinoma – What You Need to Know.”

Anti-Tumour Treatment: “Emerging trends in the treatment of advanced basal cell carcinoma.”

American Academy of Dermatology: “Skin Cancer Types: Basal Cell Carcinoma Signs and Symptoms.”

Skin Cancer Foundation: “Melanoma,” “Basal Cell Carcinoma.”

Advanced Basal Cell Carcinoma: Identification and Treatment

Approximately 1% to 10% of all basal cell carcinomas progress to an advanced stage. Not seeking care for concerning skin lesions is a big factor in the development of advanced stage skin cancer.

Basal cell carcinoma (BCC) is a type of skin cancer. Along with squamous cell carcinoma (SCC), it’s the most common of all cancer types.

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The American Cancer Society (ACS) estimates that 5.4 million basal or squamous cell carcinomas are diagnosed in the United States each year. Of these, about 80% are BCC.

Many times, BCC remains localized to a single area. However, in rarer cases, it can spread deeper into surrounding tissues or to more distant tissues. This is called advanced BCC.

The article below will cover more about advanced BCC, the symptoms to be aware of, and how this type of cancer is diagnosed and treated.

BCC is advanced when it has spread deeper into surrounding tissues or to more distant parts of the body. It’s estimated that 1% to 10 % of BCCs progress to an advanced stage.

When advanced BCC has spread from the original lesion site and deeper into surrounding skin and tissues, it’s called locally advanced BCC. While this cancer remains at the original site, the extent of its spread makes it challenging to treat.

If advanced BCC has spread from the original lesion site to more distant tissues, it’s called metastatic BCC. This type of advanced BCC is very rare, accounting for less than 1% of all BCCs.

The most common metastatic site for BCC is the lymph nodes. However, it may also spread to the bones, lungs, and liver.

Advanced BCC arises from an earlier cancerous lesion that wasn’t treated or has recurred after treatment. This type of cancer most commonly appears on areas that are frequently exposed to sunlight, such as the:

  • face
  • scalp
  • ears
  • neck
  • shoulders or upper back

The ways that BCC can present are very diverse. Some examples of potential signs of BCC can be:

  • a scaly, irritated patch of skin that’s slightly raised
  • a sore or pimple-like lesion that doesn’t heal and may ooze or bleed
  • a shiny bump that’s similar to your skin tone and may be mistaken for a mole
  • a pink or reddish area that dips in at the center
  • a flat, waxy area that looks similar to a scar

Don’t hesitate to see a doctor if you have any suspicious skin lesions

If you notice a suspicious skin lesion, especially on your scalp, face, neck, or shoulders, have a dermatologist check it out. If it’s BCC, early treatment can help to prevent advanced BCC.

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Locally advanced BCC

When BCC becomes advanced, the lesion typically becomes noticeably larger. It may also become ulcerated and not heal. As locally advanced BCC grows and spreads further, it could cause severe tissue or bone damage.

Multiple lesions may also be present in locally advanced BCC. A 2022 study of 433 people with locally advanced BCC found that almost 23.3% of participants had multiple BCC lesions. The median number of lesions was three per individual.

Metastatic BCC

The exact symptoms of metastatic BCC can vary depending upon where the cancer has spread to. However, some general symptoms to look for are:

  • fatigue
  • weakness
  • unintended weight loss
  • shortness of breath
  • pain in the area of the metastatic site

BCC is caused by DNA changes in basal skin cells that promote uncontrolled cell growth and division. Many BCCs are caused by changes affecting the hedgehog signaling pathway .

This pathway is involved in regulating cell growth and division. When it isn’t functioning as it should, the basal cells begin to grow and divide out of control.

The main driver of changes that lead to BCC is exposure to ultraviolet (UV) radiation, which is found in sunlight and in tanning beds. Other risk factors for BCC include:

  • older age
  • having light-colored skin
  • being assigned male at birth
  • having a personal or family history of nonmelanoma skin cancer
  • arsenic or radiation exposure
  • having certain inherited conditions, such as basal cell nevus syndrome or xeroderma pigmentosum
  • having a weakened immune system, which can include:
    • individuals who’ve received an organ or bone marrow transplant
    • people being treated for cancer with chemotherapy or radiation therapy
    • those who take immunosuppressive drugs
    • individuals living with HIV
    • people who have experienced repeated sunburns
    • people who’ve had thermal burns (such as from hot liquids, steam, or flames)

    BCC is typically a slow growing cancer. That means that it may take several years for it to become advanced.

    Skin cancer prevention strategies

    There are several steps that you can take in your daily life to help prevent developing BCC:

    • Always use a water-resistant sunscreen with an SPF of 30 or higher when you’ll be outside. Be sure to reapply every 2 hours.
    • Try to stay in the shade when you’re outside and aim to avoid outdoor activities when the sun’s rays are strongest. This is typically between 10:00 AM and 2:00 PM.
    • Be conscious of the fact that water, sand, and snow can reflect sunlight back at you and increase your chances of getting a sunburn.
    • Wear clothing that protects you from the sun if you’ll be outside for a while. Some examples include sunglasses, a wide-brimmed hat, and light, breathable clothing, ideally with UV protection.
    • Don’t use tanning beds and consider trying out a self-tanning product instead.
    • Do regular skin self-checks to look for any suspicious or concerning spots.

    A 2022 review notes that not seeking care for concerning skin lesions is a big factor in the development of advanced BCC. That’s why it’s so important to see a dermatologist if you’re worried about a spot on your skin.

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    In order to diagnose advanced BCC, a dermatologist will first take your medical history. They’ll ask you about topics like:

    • when you first noticed the lesion
    • if the lesion has changed in size or appearance since it first appeared
    • any other symptoms associated with the lesion, such as itching, pain, or bleeding
    • whether or not you’re having any other symptoms
    • whether you have a personal or family history of skin cancer

    They’ll then do a skin exam. During this time, they’ll evaluate the lesion both by looking at it and by using a special magnifying glass called a dermatoscope . They’ll likely examine the rest of your skin as well.

    They may also feel your lymph nodes to see if they’re swollen. This can be a sign that cancer has spread to the lymph nodes.

    Collecting a biopsy sample from the lesion is an important part of the diagnosis. A biopsy sample can be viewed under a microscope to see if cancer is present. If so, the type of cancer can also be determined.

    If your dermatologist thinks that the cancer has metastasized, they may do other tests. These can include a lymph node biopsy and imaging tests to see if there’s cancer in more distant parts of the body.

    Surgery and radiation therapy are two common treatments for BCC. In some situations, these may also be used for some types of advanced BCC.

    However, many people with advanced BCC can’t be treated with these methods due to the size of the cancer, its location, or how far it has spread.

    This means that a systemic treatment is needed. A systemic treatment is one that works throughout the whole body.

    The Food and Drug Administration (FDA) has approved three systemic treatments for advanced BCC rather recently. Let’s explore these now.

    Targeted therapy

    Targeted therapy uses drugs that target specific aspects of cancer cells. The targeted therapies used for advanced BCC are:

    • vismodegib (Erivedge), approved by the FDA in 2012
    • sonidegib (Odomzo), approved by the FDA in 2015

    Both of these drugs inhibit the hedgehog pathway. As we mentioned above, this pathway is involved in many BCCs, including advanced BCC. When the hedgehog pathway is inhibited, BCC can’t grow and spread as quickly.

    A 2018 review of studies looked into the efficacy of these drugs:

    • Locally advanced BCC: Both vismodegib and sonidegib had similar overall response rates (69% versus 57%, respectively). However, vismodegib had a higher complete response rate than sonidegib (31% versus 3%).
    • Metastatic BCC: The overall response rate for vismodegib was found to be 2.7-fold higher than that of sonidegib (39% versus 15%, respectively). The lower response rate is one of the reasons sonidegib isn’t approved for metastatic BCC.

    Immunotherapy

    Immunotherapy is a type of cancer treatment that helps to boost your immune system’s activity against a cancer. Cemiplimab (Libtayo) is an immunotherapy drug that was approved by the FDA for the treatment of advanced BCC in 2021.

    Cemiplimab is a programmed cell death 1 (PD-1) blocking antibody, which is a type of immune checkpoint inhibitor. It works by blocking immune checkpoints, which prevent immune cells from effectively finding and killing cancer cells. When the checkpoints are blocked, immune cells are free to detect and kill cancer cells. PD-1 inhibitors work well for aggressive cancers like metastatic melanoma.

    A 2021 study looked at the effectiveness of cemiplimab in people with advanced BCC for whom targeted therapy had been ineffective. Approximately 6% of participants had a complete response to cemiplimab, while 25% had a partial response.

    Generally speaking, the outlook for people with advanced BCC is poorer than that for people with an earlier stage of BCC. This is because the cancer has spread further and, as such, can be more challenging to treat.

    According to the ACS , the number of people who die due to BCC and SCC is unknown because these cancers aren’t tracked by cancer registries. It’s thought that 2,000 people in the United States die from BCC and SCC each year.

    Several factors can affect the outlook for people with advanced BCC. These include:

    • the size and location of the cancer
    • how far the cancer has spread, including if it has metastasized
    • whether or not the cancer is a recurrence of a previous BCC
    • how the cancer responds to the recommended treatment
    • your age and overall health

    If you’ve received an advanced BCC diagnosis, ask a care team about your outlook. They can evaluate the factors above to give you a better idea of what to expect individually.

    BCC becomes advanced when it has spread deeper into surrounding tissues or to more distant tissues in the body. Since BCC is a slow growing cancer, this typically happens over a period of several years.

    Advanced BCC is more difficult to treat than early BCC, often due to the location, size, and extent of the cancer. However, newer systemic treatments can help to improve your outlook when surgery or radiation therapy isn’t recommended.

    When BCC is identified and treated early, the outlook for people with this condition is very good. As such, be sure to consult a dermatologist if you notice any new or worrisome skin lesions. A dermatologist can help to determine whether it’s cancer and, if so, take steps to treat it early.

    Last medically reviewed on December 1, 2022

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Alex Koliada, PhD

Alex Koliada, PhD

Alex Koliada, PhD, is a well-known doctor. He is famous for his studies of ageing, genetics and other medical conditions. He works at the Institute of Food Biotechnology and Genomics NAS of Ukraine. His scientific researches are printed by the most reputable international magazines. Some of his works are: Differences in the gut Firmicutes to Bacteroidetes ratio across age groups in healthy Ukrainian population [BiomedCentral.com]; Mating status affects Drosophila lifespan, metabolism and antioxidant system [Science Direct]; Anise Hyssop Agastache foeniculum Increases Lifespan, Stress Resistance, and Metabolism by Affecting Free Radical Processes in Drosophila [Frontiersin].
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