Key points
- Basal cell carcinoma and squamous cell carcinoma of the skin are the most common cancers in people, and most appear on skin that has had years of sun [2, 3].
- They are different from melanoma: they are far more common, but they rarely spread to other parts of the body and are much less often fatal [3, 11].
- Important signs: a sore that does not heal, a shiny pearly bump, a red scaly patch or a lump that is growing [3].
- The main treatment is complete removal with surgery, and most patients are cured by this alone [5, 7, 46].
- If a tumour has grown so far that surgery is not possible, targeted tablets (for basal cell carcinoma) and immunotherapy (for squamous cell carcinoma) have made a big difference [5, 7].
- Sun protection and regular skin checks, especially after a kidney or other organ transplant, are the most important ways to prevent it [6, 10, 12].
What is skin cancer?
The top layer of the skin (the epidermis) has three kinds of cells: squamous cells, which are thin and flat and form the surface; round basal cells beneath them; and pigment-making cells (melanocytes) [3]. A cancer that starts in basal cells is called basal cell carcinoma (BCC), and one that starts in squamous cells is called cutaneous squamous cell carcinoma (squamous cell skin cancer). Together they are also called “non-melanoma skin cancer” [3].
These are the most common cancers. The World Health Organization’s cancer agency estimated more than 1 million new cases worldwide in 2024 [1], but because these cancers are usually not counted by cancer registries, the true number is much higher [2]. In the United States alone, more than 3 million people were treated for them in a single year [2].
Basal cell carcinoma is the more common: in people whose immune system is not weakened, it is at least 3 times as common as squamous cell carcinoma [2]. It grows slowly and almost never spreads to distant parts of the body, but if it is not treated it keeps growing where it is and can seriously damage the surrounding tissues [2]. Squamous cell carcinoma is more aggressive, and in a small number of patients (about 4 in every 100) it spreads to the lymph nodes or elsewhere [20, 8].
The good news is that most of these cancers are found early and cured with a simple treatment: in squamous cell carcinoma, more than 9 in every 10 people are fully cured after treatment [46]. In the United States, fewer than 1 in every 1,000 cancer deaths is due to these two cancers [2].
How it differs from melanoma
Melanoma is also a skin cancer, but it starts in the pigment-making cells. It is less common than basal cell and squamous cell carcinoma, but it is more likely to spread [3]. Melanoma makes up only about 1 in every 100 skin cancers, yet it causes most skin cancer deaths [11]. Its treatment and follow-up are different and are covered on the melanoma page. For the warning signs of melanoma (the ABCDE rule), see What are the symptoms of skin cancer?
This page is about basal cell carcinoma, squamous cell skin cancer and the precancerous patches caused by the sun.
Actinic keratosis: a precancerous patch caused by the sun
An actinic keratosis is a rough, scaly patch that is red, pink or brown, flat or slightly raised, and most often found on the face and the backs of the hands. Cracking and peeling of the lower lip that does not get better with lip balm or petroleum jelly can be the same kind of change [3]. These patches are not cancer, but some may later turn into squamous cell carcinoma [2].
The chance of this is very small: each year, fewer than 1 in every 1,000 patches becomes a cancer, and about a quarter of patches go away on their own within a year [4]. Even so, these patches show that the skin has had a lot of sun, so check your skin regularly. Treatment creams reduce the number of patches [17].
The “in situ” form of squamous cell carcinoma (Bowen’s disease) stays in the surface of the skin, and the chance that it turns into an invasive cancer is small (about 3 to 4 in every 100) [2].
Symptoms of skin cancer
Basal cell and squamous cell carcinoma usually show up as a change in the skin, most often in places that get sun, such as the nose, ears, lower lip and the backs of the hands [3]. The main signs are [3]:
- a sore that does not heal
- a raised, smooth, shiny, “pearly” bump
- a firm area that looks like a scar and may be white, yellow or waxy
- a raised red or reddish-brown bump
- a scaly patch that bleeds or crusts
Basal cell carcinoma is most often a shiny, pearly bump with tiny blood vessels on its surface, and the nose is its most common site. It usually causes no pain at all [2], so the absence of pain does not mean it is harmless. One type of basal cell carcinoma looks like a firm scar and has unclear edges [2]. Squamous cell carcinoma is most often found on the ears, the lower lip and the backs of the hands [2], and it can also develop in old wounds, burn scars or skin that has had radiotherapy [2].
Not every skin change is cancer, but only a doctor can find the cause, by examining the skin and, if needed, taking a biopsy [3]. More explanation, with real photographs of melanoma, is on What are the symptoms of skin cancer?
When should I see a doctor?
If you have any of these, see your GP or a dermatologist rather than waiting for it to go away on its own [3, 8]:
- a sore or spot on the skin that has not healed after a few weeks
- a new bump or patch that is growing, bleeding or changing shape
- a rough, scaly patch on the face, scalp or the back of the hand that does not go away
- a spot on an old wound, a burn scar or an area that has had radiotherapy
Go sooner, within a few days, if a spot is growing quickly, if you have pain, numbness or tingling around it, or if you feel a gland or lump near it (for example in front of the ear or in the neck) [8, 2]. If you have had a kidney, liver, heart or lung transplant, or you take drugs that suppress the immune system, show any new spot early, because these cancers behave more aggressively in you [2, 8].
Risk factors and prevention
The main cause is ultraviolet (UV) radiation from the sun and from tanning beds: the more sun the skin gets over a lifetime, the higher the risk [2, 3]. Other risk factors:
- Fair skin that burns easily and freckles, light-coloured eyes, and blond or red hair. Even so, people of any skin colour can get skin cancer [3].
- A history of sunburn and older age [3].
- A previous skin cancer or actinic keratosis, and a family history of these conditions [3].
- A weakened immune system, especially in people who take drugs that suppress the immune system after an organ transplant [2, 3]. In a large study in the United States, close to 1 in every 100 transplant recipients developed squamous cell skin cancer each year [18]. In these people, tumours behave more aggressively even when they are small [2].
- Exposure to arsenic and previous radiotherapy [2, 4].
- Long-standing wounds or inflammation of the skin (for example old ulcers), for squamous cell carcinoma [2].
- Some human papillomaviruses (HPV) that live on the skin slightly increase the risk of squamous cell carcinoma [19].
- Rare inherited conditions such as Gorlin syndrome (basal cell naevus syndrome) [3]; people with it need regular skin checks [5].
Preventing skin cancer
Sun protection is the simplest thing you can do. In a large study in Australia, adults who used sunscreen every day for four and a half years developed fewer squamous cell carcinomas, and the effect lasted for years after the study ended; no clear effect was seen on basal cell carcinoma [12, 13]. Sunscreen also prevents sunburn and new precancerous patches [4]. Guidelines advise using sunscreen together with other measures: shade, a wide-brimmed hat, covering clothing and avoiding tanning beds [8, 47].
Nicotinamide (a form of vitamin B3) has been studied in some people at high risk. In a careful study, people who had had at least 2 non-melanoma skin cancers in the previous 5 years and took 500 mg twice a day for a year developed almost a quarter fewer new skin cancers; but the effect disappeared once the tablets were stopped [14]. In organ transplant recipients the same tablets did not help [15]. The European guideline lists it with sun protection as a way of preventing skin cancer [6], but other sources do not yet consider the evidence sufficient [4, 8]. Talk to your doctor before taking it.
In people who have already had several skin cancers, one 2-to-4-week course of fluorouracil cream on the face and ears cut the need for surgery for squamous cell carcinoma in the following year by about three quarters; it had no clear effect on basal cell carcinoma [16].
How can I protect my skin from the sun?
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Shade and a hat
Outdoors, stay in the shade and wear a wide-brimmed hat [8].
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Clothes and sunglasses
Outdoors, wear long-sleeved shirts, long trousers and sunglasses [47].
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Know your skin
Look at your skin in a mirror from time to time and show your doctor any new or changing spot. Family members can check places such as your back [8].
Skin checks and screening
For people with no signs or history of skin cancer, the US Preventive Services Task Force finds the evidence insufficient to recommend regular skin examinations by a doctor [11]. People at high risk are different: anyone who has had a squamous cell carcinoma should have their skin examined by a doctor at least once a year [8], and organ transplant recipients need skin checks for life [10]. See which screening tests suit your age and sex in the screening tool.
Diagnosis and staging
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How skin cancer is diagnosed
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Skin examination
The doctor checks the spot and the rest of your skin for unusual colour, size, shape or texture, and asks about your own and your family’s history [3].
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Biopsy
All or part of the spot is removed and examined under a microscope: by shaving off the surface, by a punch biopsy (removing a small round piece), by removing part of the spot or by removing all of it [3]. Squamous cell carcinoma is always confirmed with a biopsy, and in basal cell carcinoma a biopsy is needed whenever the diagnosis is not certain [6, 5]. Read more: Does a biopsy spread cancer?
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Low-risk and high-risk skin cancer
Most basal cell and squamous cell carcinomas are “low-risk” and are cured with a simple treatment. Based on a few features, the doctor decides whether a tumour is “high-risk”, meaning it is more likely to come back or spread and needs more careful treatment [8, 9]:
- a larger size, especially on the face, ears, lips, hands, feet or genitals
- unclear edges, or a tumour that has come back after treatment
- a weakened immune system, or previous radiotherapy to the same area
- fast growth, or pain and numbness, which suggest that a nerve is involved
- deep growth or an aggressive type in the pathology report
Squamous cell carcinoma is also given a stage (from 0 to 4); most tumours are at the lower stages [3, 21]. General explanation: What are cancer stages?
For physicians
| Feature | Low risk | High risk |
|---|---|---|
| Location and size | Area L under 20 mm; area M under 10 mm | Area L 20 mm or more; area M 10 mm or more; area H at any size |
| Borders | Well defined | Poorly defined |
| Primary or recurrent | Primary | Recurrent |
| Immunosuppression | No | Yes |
| Site of prior radiotherapy or chronic inflammatory process | No | Yes |
| Rapidly growing tumour | No | Yes |
| Neurological symptoms | No | Yes |
| Degree of differentiation | Well to moderately differentiated | Poorly differentiated |
| High-risk histological subtype (adenoid or acantholytic, adenosquamous, desmoplastic, metaplastic) | No | Yes |
| Depth (thickness or Clark level) | Under 2 mm, or level I to III | 2 mm or more, or level IV and V |
| Perineural, lymphatic or vascular involvement | No | Yes |
Area L: trunk and extremities (excluding hands, feet, nail units, pretibia and ankles); area M: cheeks, forehead, scalp, neck and pretibia; area H: central face, eyelids, eyebrows, periorbital skin, nose, lips, chin, mandible, preauricular and postauricular skin and sulci, temple, ear, genitalia, hands and feet. Diameter includes the surrounding rim of erythema, and area H is high risk regardless of size. This is the NCCN stratification as reproduced in the 2018 AAD guideline [8]; the BAD guideline divides cSCC into three groups: low, high and very high risk [10].
| System and stage | Criteria |
|---|---|
| AJCC Tis | Carcinoma in situ |
| AJCC T1 | Tumour 2 cm or smaller in greatest dimension |
| AJCC T2 | More than 2 cm and up to 4 cm |
| AJCC T3 | More than 4 cm, or minor bone erosion, or perineural invasion, or deep invasion |
| AJCC T4a | Gross cortical bone or marrow invasion |
| AJCC T4b | Skull base invasion or skull base foramen involvement |
| BWH T1 | No risk factors |
| BWH T2a | One risk factor |
| BWH T2b | 2 to 3 risk factors |
| BWH T3 | 4 risk factors or bone invasion |
Deep invasion in AJCC: beyond the subcutaneous fat or more than 6 mm (measured from the granular layer of the adjacent normal epidermis to the base of the tumour); perineural invasion for T3: tumour cells in the nerve sheath of a nerve deeper than the dermis or measuring 0.1 mm or more in calibre, or clinical or radiological involvement of named nerves without skull base invasion [2]. BWH risk factors: diameter 2 cm or more, poor differentiation, perineural invasion and invasion beyond the subcutaneous fat; bone invasion is automatically T3 [8]. In 1,818 tumours, BWH T2b and T3 made up only 5% of tumours but accounted for 60% of poor outcomes, 70% of nodal metastases and 83% of disease-specific deaths [21].
| Feature | Low risk | High risk (one criterion is enough) |
|---|---|---|
| Location and size | Area L 20 mm or less; area M 10 mm or less | Area L over 20 mm; area M over 10 mm; area H at any size |
| Borders | Well defined | Poorly defined |
| Primary or recurrent | Primary | Recurrent |
| Immunosuppression | No | Yes |
| Site of prior radiotherapy | No | Yes |
| Growth pattern | Nodular or superficial | Infiltrative, morphoeic or micronodular |
| Basosquamous differentiation | No | Yes |
| Depth of invasion | Limited to the dermis or subcutaneous fat; 6 mm or less | Beyond the subcutaneous fat; more than 6 mm |
| Perineural invasion | No | Yes |
| Pathological stage | pT1 (20 mm or less) | pT2 to pT4 |
| Histological margin | Not involved (1 mm or more) | Involved (0 mm) or close (under 1 mm) |
Areas H, M and L are defined in the note to the NCCN table above [8]. EADO divides basal cell carcinomas into “easy-to-treat” (common) and “difficult-to-treat”, and leaves decisions on the second group to a multidisciplinary tumour board [5].
Treatment of skin cancer
Almost all basal cell and squamous cell carcinomas can be cured. The main treatment is complete removal of the tumour with surgery [5, 7]. The choice of method depends on the type of tumour, its size and site, whether it is low-risk or high-risk, and your general health [3]. With the right method, about 9 in every 10 people with basal cell carcinoma have no recurrence after treatment [2].
Ways of treating skin cancer
Surgery with a clear margin
Mohs surgery
The tumour is removed layer by layer, and each layer is checked under a microscope straight away until no cancer is left. Less healthy skin is removed, and it suits the face, tumours that have come back and high-risk tumours [2, 5]. In a 10-year study of high-risk basal cell carcinomas of the face, fewer tumours came back with this method [22].
Scraping and burning (curettage)
Freezing (cryotherapy)
The tumour is frozen and destroyed with liquid nitrogen. It is used for small tumours with clear edges, especially in people for whom surgery is not suitable. The treated skin stays permanently paler [2].
Treatment creams
Imiquimod or fluorouracil cream is applied for several weeks to a low-risk superficial basal cell carcinoma or to precancerous patches, and the skin becomes red and inflamed during this time [5, 43, 44]. The results are not as good as surgery: in one study, 5 years later almost everyone treated with surgery and about 8 in every 10 treated with cream were free of recurrence [23].
Light treatment (photodynamic therapy)
Radiotherapy
For people for whom surgery would be difficult or unsuitable, especially older people, or when surgery would change the face a lot (for example on the nose or ear) [5, 2]. It is sometimes also given after surgery for high-risk tumours [10]. Read more: What is radiotherapy?
Tablets and immunotherapy for advanced disease
When a tumour has become large and deep or has spread, and surgery or radiotherapy is not possible: tablets that block the tumour’s growth pathway for basal cell carcinoma, and immunotherapy for squamous cell carcinoma [5, 7]. Read more: What is cancer immunotherapy?
Treatment of basal cell carcinoma
The first treatment for basal cell carcinoma is complete removal with surgery [5]. For low-risk tumours, usually 4 mm of healthy skin around it is also removed, and for high-risk tumours at least 5 mm [9]. For high-risk tumours, tumours that have come back, or tumours in sensitive areas of the face such as the eyelids, nose and lips, Mohs surgery is recommended [5, 2].
For superficial, low-risk basal cell carcinoma, creams (imiquimod or fluorouracil), scraping and burning, freezing or light treatment are also options [5, 9]. These leave less scarring, but the cancer is more likely to come back, so follow-up is needed [23, 24]. For people who cannot have or do not want surgery, especially older people, radiotherapy is a good alternative [5]; but radiotherapy is usually avoided in Gorlin syndrome [2, 9].
Basal cell carcinoma only rarely grows so far that surgery or radiotherapy is no longer possible. In that case the tablets vismodegib or sonidegib are used; they block the tumour’s growth pathway (the hedgehog pathway) [5]. In locally advanced tumours, the tumour shrinks in about half of patients, and less often when the disease has spread [25, 26, 42]. If these tablets do not work or cannot be tolerated, immunotherapy with cemiplimab is the next option [5, 28]. These tablets can seriously harm an unborn baby, so reliable contraception is essential [41, 42].
Treatment of squamous cell carcinoma
Squamous cell carcinoma is also usually treated with surgery: removal with a margin of healthy skin and a check of the edges, or Mohs surgery [7]. The most important point is that the edges are completely clear [7]. For low-risk tumours at least 4 mm of healthy skin is removed, and more for high-risk tumours [10, 8]. Small (under 1 cm), well-defined, low-risk tumours can sometimes be treated by scraping and burning [2, 10].
If surgery is not possible or suitable, radiotherapy is the main treatment [7]. After surgery for some high-risk tumours, for example when the edges are very close, or when the tumour was not completely removed and further surgery is not possible, radiotherapy is also given [10]. If the cancer has reached the lymph nodes, a multidisciplinary team decides on surgery to the nodes and other treatments [7].
In advanced squamous cell carcinoma that cannot be cured with surgery or radiotherapy, immunotherapy with anti-PD-1 drugs, that is pembrolizumab or cemiplimab, is the first treatment [7, 2], and it shrinks the tumour in a third to a half of patients [31, 33]. In high-risk patients who have had surgery and radiotherapy, about a year of immunotherapy with cemiplimab made the cancer much less likely to come back [36]; this decision is made by the treatment team [7]. Immunotherapy before surgery gave very good results in one study, but it is not yet an approved treatment [34, 35, 39]. In organ transplant recipients, immunotherapy may cause rejection of the transplanted organ and has to be weighed carefully [39, 40].
Treatment of actinic keratosis
For precancerous patches, whether single or many in one area, there are several options: freezing, scraping, creams, chemical peels, light treatment or laser [2]. In a large study of patients with many patches on the head, fluorouracil cream worked better than three other common methods (imiquimod cream, light treatment and ingenol gel) [17]. During treatment with this cream, the skin becomes red, blistered and scaly, and full healing may only be seen 1 to 2 months after the treatment ends [44].
- Do not delay treatment: left alone, a basal cell carcinoma grows deeper where it is and can destroy the surrounding tissues [2].
- Ask about the pathology report: are the edges clear? Is the tumour low-risk or high-risk? [7, 8]
- Keep an eye on your skin for years: anyone who has had one skin cancer has a high chance of getting a new one [8, 2].
Life after treatment and follow-up
After treatment, the chance of a new skin cancer is high, because skin that has had a lot of sun is still the same skin [2]. In one study, about 4 in every 10 people developed another skin cancer within 5 years of their first non-melanoma skin cancer [8]. Their risk of melanoma is also higher [8].
Follow-up depends on the level of risk. After a high-risk basal cell carcinoma, multiple basal cell carcinomas or Gorlin syndrome, long-term follow-up is recommended [5]. After a squamous cell carcinoma, a skin examination is needed at least once a year [8], and for high-risk tumours every 4 to 6 months in the first 2 years [10]. Almost all recurrences of squamous cell carcinoma happen in the first 5 years [2].
What you can do yourself: protect yourself from the sun, look at your skin regularly and show any new or changing spot early [8]. Read more: What is cancer recurrence and how is it followed up?
What should I do after the diagnosis?
Frequently asked questions
What is basal cell carcinoma?
Basal cell carcinoma is the most common skin cancer and starts in the cells of the lower layer of the epidermis [3, 2]. It is most often seen on the face, especially the nose, as a shiny, pearly bump or a sore that does not heal [2, 3]. It grows slowly and almost never spreads, but it must be removed completely so that it does not keep growing where it is [2, 5].
Is skin cancer deadly?
Basal cell carcinoma is almost never fatal, because it rarely spreads [2]. Squamous cell carcinoma is also usually curable, and more than 9 in every 10 patients are fully cured [46]. The risk is higher with large, deep or recurrent tumours and in people with a weak immune system [20, 8]. Melanoma is a different story; see the melanoma page.
Can skin cancer come back after surgery?
Sometimes. The chance of recurrence depends on the type of tumour, its site and the treatment method, and some basal cell carcinomas come back even after 5 years [2, 22]. Anyone who has had one skin cancer can also get a new one elsewhere on the skin [8]. That is why follow-up and skin checks matter.
What is Mohs surgery and who needs it?
In Mohs surgery, the tumour is removed layer by layer and each layer is checked under a microscope straight away until the edges are clear; this removes as little healthy skin as possible [2]. It is recommended for high-risk tumours, tumours that have come back or have unclear edges, and for sensitive areas such as the eyelids, nose, lips and ears [2, 5, 8]. It takes more time and costs more [2].
Is a cream enough to treat skin cancer?
Only for some tumours. Imiquimod or fluorouracil cream is used for superficial, low-risk basal cell carcinoma and for precancerous patches [5, 43, 44]. Creams are not suitable for high-risk basal cell carcinoma [9], and invasive squamous cell carcinoma is better treated with surgery [8]. In one study, 5 years after treatment, almost everyone treated with surgery and about 8 in every 10 treated with cream were free of recurrence [23].
Does sunscreen really prevent skin cancer?
Do people with dark skin get skin cancer too?
I have had a kidney transplant; what should I do?
Because of their immune-suppressing drugs, organ transplant recipients get skin cancer, especially squamous cell carcinoma, more often, and these tumours are more aggressive [2, 18, 8]. Protect yourself from the sun, look at your skin regularly and have skin checks for life [10]. If you have many skin cancers, your doctor may change your immune-suppressing drugs [8]. Nicotinamide tablets did not help in a study of transplant recipients [15].
How is advanced skin cancer treated?
When surgery and radiotherapy are not possible: for basal cell carcinoma, the tablets vismodegib or sonidegib and, if they fail, immunotherapy with cemiplimab [5]; for squamous cell carcinoma, immunotherapy with pembrolizumab or cemiplimab [7, 2]. These drugs shrink the tumour in a large share of patients, and in many of them the effect lasts [26, 31, 33]. Read about side effects in the guide to immunotherapy side effects.
Evidence and recent advances (for physicians)
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Risk stratification, staging and imaging
In the prospective Brantsch cohort (615 patients treated with surgery and three-dimensional margin histology; median follow-up 43 months), metastasis occurred in 4% and local recurrence in 3%. Tumours 2 mm thick or less did not metastasise; those 2.1 to 6 mm thick metastasised in 4% and those thicker than 6 mm in 16%. Independent factors for metastasis were thickness (HR 4.79), immunosuppression (HR 4.32), location on the ear (HR 3.61) and horizontal size (HR 2.22); factors for local recurrence were thickness (HR 6.03) and desmoplastic growth (HR 16.11) [20]. Metastasis rates of 5% for tumours on sun-exposed skin, 9% for the ear and 14% for the lip have been reported, and about 38% for carcinomas arising in scars or on non-sun-exposed skin; 96% of metastases are diagnosed within the first 5 years [2].
In 1,818 primary tumours at BWH, AJCC and UICC T3 and T4 were indistinct, and most poor outcomes (86% with AJCC) occurred in low stages; by contrast, BWH T2b/T3, with 5% of tumours, accounted for 60% of poor outcomes. The cumulative incidences of local recurrence, nodal metastasis and disease-specific death were 1.4%, 0.6% and 0.2% for T1/T2a and 24%, 24% and 16% for T2b/T3 [21]. The AAD recommends the NCCN framework for clinical stratification and the BWH system for the most accurate prognosis; nodal imaging (CT, PET/CT or ultrasound) may be considered for BWH T2b or higher tumours, and the value of sentinel lymph node biopsy remains unclear [8]. In solid organ transplant recipients, the risk of metastasis may be 2 to 3 times higher [8].
The 2026 update of the EADO guideline divides cSCC into “easy-to-treat” (the majority) and “difficult-to-treat”, and proposes five difficult-to-treat groups: groups 1 and 2 are common cSCC that is complex to treat because of tumour or patient features or multiplicity, group 3 is locally advanced disease, and groups 4 and 5 are regional or distant metastases. AJCC8 and BWH are the most widely used staging systems [6].
Local treatment: margins, Mohs surgery and non-surgical treatments
Surgical margins: the BAD recommends a 4 mm peripheral clinical margin for low-risk BCC and at least 5 mm for primary BCC with a high-risk factor [9]. For cSCC, the BAD recommends a margin of 4 mm or more (low risk), 6 mm or more (high risk) and 10 mm or more (very high risk) [10], and the AAD recommends excision of low-risk primary cSCC with a 4 to 6 mm margin to the depth of the mid-subcutaneous fat with histological margin assessment [8]. In a prospective series of 141 cSCCs, a 4 mm margin was adequate in more than 95% of well-differentiated tumours up to 19 mm in diameter, whereas larger or less-differentiated tumours and those in high-risk sites needed 6 to 10 mm margins [2]. EADO considers surgery with post-operative margin assessment or micrographically controlled surgery the first-line treatment for both tumours [5, 7].
Mohs surgery: in the Dutch randomised trial (408 high-risk primary facial BCCs and 204 recurrent BCCs), the 10-year cumulative probability of recurrence was 4.4% with Mohs vs 12.2% with standard excision for primary BCC (P=0.100) and 3.9% vs 13.5% for recurrent BCC (P=0.023); 56% of recurrences of primary BCC occurred after 5 years [22]. In the same trial, operative costs with Mohs were almost twice as high [2]. The BAD recommends offering Mohs as a first-line option for recurrent BCC with at least one other high-risk factor and considering it for high-risk primary BCC [9]; the AAD recommends Mohs for high-risk cSCC [8].
Non-surgical treatments: in the SINS trial (superficial or nodular BCC at low-risk sites), 5-year success was 82.5% with imiquimod vs 97.7% with surgery with a 4 mm margin (RR 0.84; 95% CI 0.77 to 0.91), and most imiquimod failures occurred in the first year [23]. In superficial BCC (601 patients), 5-year tumour-free survival was 80.5% with imiquimod, 70.0% with fluorouracil and 62.7% with MAL photodynamic therapy, and imiquimod was superior to both [24]. In the imiquimod registration trials, clinical and histological clearance 12 weeks after treatment of superficial BCC was 75% vs 2% with vehicle [43]. Curettage and electrodesiccation is used in cSCC only for small (under 1 cm), well-defined, well-differentiated tumours [2], and not on terminal hair-bearing skin (scalp, pubic and axillary regions, and the beard area) [8]; in BCC of the neck, trunk and extremities, the 5-year recurrence rate after it was 3.3% [2]. In a trial of excision versus radiotherapy for facial BCC smaller than 4 cm, 4-year failure was 0.7% vs 7.5% (P=0.003) [2].
Actinic keratosis and field-directed prevention: in 624 patients with 5 or more lesions in one continuous 25 to 100 cm² area on the head, the probability of remaining free from treatment failure 12 months after the end of treatment was 74.7% with 5% fluorouracil, 53.9% with 5% imiquimod, 37.7% with MAL photodynamic therapy and 28.9% with ingenol mebutate (HR for failure vs fluorouracil: 2.03, 2.73 and 3.33) [17]. In the VA trial (932 veterans with at least 2 keratinocyte carcinomas in the previous 5 years), one 2-to-4-week course of 5% fluorouracil on the face and ears reduced cSCC requiring surgery in the first year by 75% (1% vs 4%; P=0.002), with no significant effect on BCC or over the whole 4-year period [16]. Progression of actinic keratosis to cSCC is about 0.075% to 0.096% per year [4].
Advanced BCC: hedgehog inhibitors and cemiplimab
In ERIVANCE (vismodegib 150 mg daily), the independently assessed objective response rate was 30% in 33 metastatic patients and 43% in 63 locally advanced patients (complete response 21%), with a median duration of response of 7.6 months; serious adverse events occurred in 25% [25]. In the final update (39 months after the end of accrual), the investigator-assessed response rate was 48.5% (metastatic) and 60.3% (locally advanced), the median duration of response 14.8 and 26.2 months, and median overall survival in the metastatic group 33.4 months [26]. In BOLT, sonidegib 200 mg gave responses in 43% of locally advanced and 15% of metastatic patients and, compared with 800 mg, led to fewer dose interruptions or reductions (32% vs 60%) and discontinuations (22% vs 36%) [27]; with at least 30 months of follow-up, the response rate in locally advanced disease was 56% with a median duration of response of 26.1 months [42]. Sonidegib is approved only for locally advanced BCC, and vismodegib for both locally advanced and metastatic disease [41, 42].
After a hedgehog inhibitor, cemiplimab 350 mg every 3 weeks gave a response rate of 31% (complete 6%) in 84 locally advanced patients, with grade 3 to 4 adverse events in 48% and no treatment-related deaths [28]. In the final analysis of 54 metastatic patients, the response rate was 22%, disease control 63%, median progression-free survival 10 months and median overall survival 50 months [29]. EADO recommends hedgehog inhibitors for locally advanced and metastatic BCC, and cemiplimab as second line after progression, contraindication or intolerance [5].
Advanced cSCC: immunotherapy and later options
In KEYNOTE-629 (pembrolizumab 200 mg every 3 weeks for up to 35 cycles), the objective response rate in 105 recurrent or metastatic patients was 34.3% (4 complete responses), median progression-free survival 6.9 months and treatment-related grade 3 to 5 adverse events 5.7% [32]; in a later analysis, the response rate was 50.0% (complete 16.7%) in 54 locally advanced patients and 35.2% in the recurrent or metastatic group [33]. With longer follow-up, the FDA label reports response rates of 35% and 52% and a median duration of response of 47.2 months in locally advanced disease [40].
In EMPOWER-CSCC-1, cemiplimab produced responses in 28 of 59 patients (47%) in the phase 2 metastatic group [30]; in the final analysis of groups 1 to 3 (193 patients, 42.5 months of follow-up), the response rate was 47.2%, the estimated 12-month duration of response 88.3% and median progression-free survival 26.0 months [31]. Patients with an organ transplant, autoimmune disease needing systemic immunosuppressive treatment within the previous 5 years or ECOG 2 or more were excluded from these studies [39]. EADO 2026 considers anti-PD-1 agents the first-line systemic treatment for metastatic or locally advanced cSCC not amenable to curative surgery or radiotherapy, and lists clinical trials, an EGFR inhibitor (cetuximab) combined with anti-PD-1, chemotherapy or radiotherapy as second-line options [7]. First-line single-agent cetuximab in 36 patients with a median age of 79 years achieved a 6-week disease control rate of 69% (8 partial and 2 complete responses) [38].
Treatment before and after surgery in high-risk cSCC
Before surgery (neoadjuvant): in a confirmatory, non-randomised phase 2 trial (79 patients with resectable cSCC of stage II with a primary tumour of at least 3 cm, stage III or stage IV without distant metastasis; 91% head and neck), cemiplimab 350 mg every 3 weeks for up to 4 doses before surgery gave a pathological complete response in 51% and a major pathological response in 13% on independent review, and an imaging response in 68%; grade 3 or higher adverse events occurred in 18%, 4 fatal events were reported (three most likely related to underlying heart disease) and 9 patients (11%) did not have surgery within the planned window [34]. In the final analysis, with a median follow-up of 54 months, 54-month event-free survival was 76.2% and overall survival 79.4%; none of the 40 patients with a pathological complete response relapsed, and all 5 new events were deaths from coexisting illnesses without recurrence [35]. This approach has no randomised comparison and is not in the FDA label [34, 39].
After surgery (adjuvant): in C-POST (phase 3; 415 patients after surgery and radiotherapy with high-risk nodal features, namely extracapsular extension with the largest node 20 mm or more or at least 3 involved nodes, or non-nodal features, namely in-transit metastases, T4 with bone invasion, perineural invasion or a locally recurrent tumour with at least one other high-risk feature), cemiplimab improved disease-free survival (24 vs 65 events; HR 0.32; 95% CI 0.20 to 0.51; 24-month disease-free survival 87.1% vs 64.1%) and reduced locoregional (HR 0.20) and distant (HR 0.35) recurrence; grade 3 or higher adverse events occurred in 23.9% vs 14.2% and discontinuation because of adverse events in 9.8% vs 1.5% [36]. By contrast, the phase 3 KEYNOTE-630 trial of adjuvant pembrolizumab did not meet its primary endpoint and has not yet been fully published; indirect comparisons of the two trials are only hypothesis-generating [37]. EADO leaves the decision on adjuvant cemiplimab to the multidisciplinary tumour board [7].
Adjuvant radiotherapy: the BAD advises considering adjuvant radiotherapy for clear but close margins (under 1 mm) after multidisciplinary discussion and for completely excised T3 tumours with multiple high-risk factors, and recommends it after incomplete excision when further surgery is not possible [10]. According to EADO 2023, in high-risk localised cSCC with clear margins, the current evidence has not shown a significant benefit of adjuvant radiotherapy for patients with at least one high-risk factor [48].
- Neoadjuvant cemiplimab in cSCC has been studied only in a non-randomised phase 2 trial and is not in the FDA label; weigh its use in a tumour board, ideally within a clinical trial [34, 35, 39].
- Adjuvant pembrolizumab (KEYNOTE-630) showed no benefit; the only adjuvant drug with proven benefit is cemiplimab after surgery and radiotherapy [37, 36].
- Nicotinamide did not help organ transplant recipients, and in immunocompetent people its effect disappears when it is stopped [15, 14].
- PD-1 inhibitors carry a risk of graft rejection in solid organ transplant recipients, and these patients were excluded from the pivotal trials [39, 40].
Treatment regimens and doses (for physicians)
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Treatment regimens and doses: index13 regimens
- PD-1 inhibitors (pembrolizumab and cemiplimab): no dose reduction is recommended. Withhold for severe (grade 3) immune-mediated adverse reactions; permanently discontinue for grade 4 reactions, recurrent grade 3 reactions requiring systemic immunosuppression, or inability to reduce prednisone to 10 mg a day or less within 12 weeks. Check liver enzymes, creatinine and thyroid function at baseline and periodically [39, 40]. Solid organ transplant rejection is a known immune-mediated adverse reaction [39, 40]. Read more: immunotherapy toxicity.
- Vismodegib and sonidegib, embryo-fetal toxicity (boxed warning): verify pregnancy status before starting (vismodegib: within 7 days before starting). Effective contraception for 24 months (vismodegib) or at least 20 months (sonidegib) after the last dose; men must use condoms, even after vasectomy, for 3 months (vismodegib) or at least 8 months (sonidegib). Blood donation is not allowed for 24 months (vismodegib) or 20 months (sonidegib), and semen donation for 3 months after vismodegib [41, 42].
- Common adverse reactions of hedgehog inhibitors: muscle spasms (72% with vismodegib and 54% with sonidegib), alopecia (64% and 53%), dysgeusia (55% and 46%), weight loss (45% and 30%) and fatigue (40% and 41%). With sonidegib, measure CK and creatinine before starting, periodically and if muscle symptoms occur, and avoid strong CYP3A inhibitors, use of moderate CYP3A inhibitors for more than 14 days, and strong and moderate CYP3A inducers. Premature fusion of the epiphyses has been reported in children [41, 42].
- Fluorouracil cream: contraindicated in pregnancy and should not be used in DPD enzyme deficiency; avoid contact with mucous membranes, eyelids and eyes, and avoid ultraviolet light during treatment [44]. DPYD testing.
- Imiquimod cream: local skin reactions (weeping and erosion) can occur after a few applications, and a rest of several days is allowed; it may exacerbate inflammatory skin conditions, including chronic GVHD [43].
Local treatment: actinic keratosis and superficial BCC, and prevention
Imiquimod 5% cream for superficial BCC
Biopsy-confirmed primary superficial BCC in an immunocompetent adult, maximum diameter 2 cm, on the trunk (excluding anogenital skin), neck or extremities (excluding hands and feet), when surgery is less appropriate and follow-up can be assuredCycle length: 5 times a week
Biopsy-confirmed primary superficial BCC in an immunocompetent adult, maximum diameter 2 cm, on the trunk (excluding anogenital skin), neck or extremities (excluding hands and feet), when surgery is less appropriate and follow-up can be assured
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Imiquimod 5% cream | Tumour diameter 0.5 to under 1 cm: about 10 mg (4 mm droplet); 1 to under 1.5 cm: about 25 mg (5 mm droplet); 1.5 to 2 cm: about 40 mg (7 mm droplet) | Topical, to the tumour and 1 cm of surrounding skin | Once a day before bedtime, 5 days a week; leave on for about 8 hours, then wash off |
Imiquimod 5% cream for actinic keratosis
Typical, non-hyperkeratotic, non-hypertrophic actinic keratosis of the face or scalp in an immunocompetent adultCycle length: Twice a week
Typical, non-hyperkeratotic, non-hypertrophic actinic keratosis of the face or scalp in an immunocompetent adult
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Imiquimod 5% cream | No more than 1 packet per application | Topical, to one continuous area of about 25 cm² (face or scalp, not both at the same time) | Once before bedtime, twice a week; leave on for about 8 hours |
Fluorouracil 5% cream for superficial BCC
Histologically diagnosed superficial BCC when conventional methods are impractical (multiple lesions or difficult sites); for isolated, easily accessible BCC, surgery is preferredCycle length: Twice a day
Histologically diagnosed superficial BCC when conventional methods are impractical (multiple lesions or difficult sites); for isolated, easily accessible BCC, surgery is preferred
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Fluorouracil 5% cream or solution | Enough to cover the lesion | Topical | Twice a day |
Fluorouracil cream for actinic keratosis
Multiple actinic keratoses; field treatmentCycle length: Twice a day
Multiple actinic keratoses; field treatment
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Fluorouracil cream or solution | Enough to cover the lesions | Topical | Twice a day until the inflammatory response reaches the erosion stage |
Oral nicotinamide for prevention (ONTRAC trial dose)
Immunocompetent patients with at least 2 non-melanoma skin cancers in the previous 5 years; not effective in organ transplant recipientsCycle length: Daily, continuous
Immunocompetent patients with at least 2 non-melanoma skin cancers in the previous 5 years; not effective in organ transplant recipients
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Nicotinamide | 500 mg | Oral | Twice a day |
Dose as in the ONTRAC trial; this supplement has no FDA label for this use [14]. In ONTRANS (transplant recipients, same dose) it gave no benefit [15]. EADO 2026 lists it alongside sun protection [6]; the 2018 AAD guideline considered the evidence insufficient for a recommendation [8].
Evidence: ONTRAC (2015)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Advanced BCC (locally advanced or metastatic)
Vismodegib for advanced BCC
Metastatic BCC, or locally advanced BCC that has recurred after surgery or in a patient who is not a candidate for surgery and radiotherapyCycle length: Continuous
Metastatic BCC, or locally advanced BCC that has recurred after surgery or in a patient who is not a candidate for surgery and radiotherapy
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Vismodegib | 150 mg | Oral, with or without food; swallow capsules whole | Once a day, continuously |
Per the FDA label [41]. Withhold for up to 8 weeks for intolerable adverse reactions; permanently discontinue for severe cutaneous adverse reactions (SJS, TEN, DRESS); interrupt for severe musculoskeletal reactions and discontinue if they recur. A missed dose is not made up [41]. Evidence: [25, 26]; place in therapy: [5].
Evidence: ERIVANCE BCC (2012)
Sonidegib for locally advanced BCC
Locally advanced BCC that has recurred after surgery or radiotherapy, or in a patient who is not a candidate for themCycle length: Continuous
Locally advanced BCC that has recurred after surgery or radiotherapy, or in a patient who is not a candidate for them
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Sonidegib | 200 mg | Oral, on an empty stomach (at least 1 hour before or 2 hours after a meal) | Once a day, continuously |
Per the FDA label [42]. CK and renal function tests before starting. Interrupt for severe or intolerable musculoskeletal reactions, a first CK rise between 2.5 and 10 times the upper limit or a recurrent rise between 2.5 and 5 times, and resume at 200 mg once symptoms resolve; permanently discontinue for CK above 2.5 times the upper limit with worsening renal function, CK above 10 times, a recurrent rise above 5 times, or recurrent severe musculoskeletal reactions [42]. Evidence: [27]; place in therapy: [5].
Cemiplimab for BCC after a hedgehog inhibitor
Locally advanced or metastatic BCC previously treated with a hedgehog inhibitor, or when these drugs are not appropriateCycle length: Every 21 days
Locally advanced or metastatic BCC previously treated with a hedgehog inhibitor, or when these drugs are not appropriate
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cemiplimab | 350 mg | IV infusion over 30 minutes | Day 1 every 3 weeks |
Evidence: Study 1620 (2021)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Advanced cSCC (metastatic or locally advanced, not curable with local treatment)
Pembrolizumab for advanced cSCC
Recurrent or metastatic cutaneous SCC, or locally advanced disease not curable with surgery or radiotherapy
Recurrent or metastatic cutaneous SCC, or locally advanced disease not curable with surgery or radiotherapy
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg (or 400 mg) | IV infusion over 30 minutes | 200 mg every 3 weeks or 400 mg every 6 weeks |
Per the FDA label [40]. Evidence: [32, 33]. The trial excluded patients with autoimmune disease or needing immunosuppression [40].
Evidence: KEYNOTE-629 (2020)
Cemiplimab for advanced cSCC
Metastatic or locally advanced cutaneous SCC in patients who are not candidates for curative surgery or curative radiotherapyCycle length: Every 21 days
Metastatic or locally advanced cutaneous SCC in patients who are not candidates for curative surgery or curative radiotherapy
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cemiplimab | 350 mg | IV infusion over 30 minutes | Day 1 every 3 weeks |
Evidence: PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma (2018)
Single-agent cetuximab (off-label in cutaneous SCC)
Unresectable advanced cSCC, especially in older patients or when anti-PD-1 therapy is not possible or not effective; EADO 2026 lists EGFR inhibitors among second-line optionsCycle length: Weekly
Unresectable advanced cSCC, especially in older patients or when anti-PD-1 therapy is not possible or not effective; EADO 2026 lists EGFR inhibitors among second-line options
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cetuximab | First dose 400 mg/m², then 250 mg/m² | IV | Weekly |
Dose as in the Maubec phase 2 trial [38]; cutaneous SCC is not among the FDA-labelled indications. Per the label: premedicate with an H1 receptor antagonist; immediately and permanently discontinue for serious infusion reactions; monitor electrolytes (magnesium, potassium and calcium) during treatment and for at least 8 weeks afterwards [45]. Place in therapy: [7].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
High-risk resectable cSCC: before and after surgery
Adjuvant cemiplimab (C-POST)
cSCC at high risk of recurrence after surgery and radiotherapy (high-risk nodal or non-nodal features as in C-POST); decision in the tumour board
cSCC at high risk of recurrence after surgery and radiotherapy (high-risk nodal or non-nodal features as in C-POST); decision in the tumour board
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Phase 1 | |||
| Cemiplimab | 350 mg | IV infusion over 30 minutes | Every 3 weeks for 12 weeks |
| Phase 2 | |||
| Cemiplimab | 700 mg (or continue 350 mg every 3 weeks) | IV infusion over 30 minutes | Every 6 weeks |
Per the FDA label [39]. In C-POST, adjuvant radiotherapy had to be completed 2 to 10 weeks before randomisation, and the benefit was similar with both dosing schedules [39]. Evidence: [36]; place in therapy: [7].
Evidence: C-POST (2025)
Neoadjuvant cemiplimab (investigational)
Resectable cSCC of stage II (primary tumour at least 3 cm), III or IV without distant metastasis, ECOG 0 or 1; off-label, ideally within a trial or after tumour board discussionCycle length: Every 21 days
Resectable cSCC of stage II (primary tumour at least 3 cm), III or IV without distant metastasis, ECOG 0 or 1; off-label, ideally within a trial or after tumour board discussion
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cemiplimab | 350 mg | IV | Every 3 weeks (days 1, 22, 43 and 64) |
Dose and schedule as in the phase 2 trial [34]; this use is not in the FDA label [39]. Imaging at weeks 6 and 12 to detect progression; 11% of patients did not have surgery within the planned window [34]. Final follow-up: [35].
Evidence: Neoadjuvant cemiplimab (2022)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Scientific evidence
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Key studies
7 itemsPembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629)
A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention
PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma
Efficacy and safety of vismodegib in advanced basal-cell carcinoma
Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma
Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma
Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial
Selected guidelines
2 itemsEuropean consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment - update 2026
European consensus-based interdisciplinary guideline for diagnosis and treatment of basal cell carcinoma—update 2023
Common questions
Related drugs
References
48 referencesShow all references, 10 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1Non-melanoma skin cancer fact sheet (GLOBOCAN 2024)
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- 19Association Between β-Genus Human Papillomavirus and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals-A Meta-analysis
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- 30PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma
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- 32Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629)
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- 45ERBITUX (cetuximab) injection, for intravenous use: Prescribing Information
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- 48European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment-Update 2023
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