Squamous cell carcinoma of the skin

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

SCC in situ (Bowen's disease)

1st line – destructive therapies

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1st line –

destructive therapies

Destructive therapy may include ablative laser vermilionectomy, ablative skin resurfacing, chemical peels, cryotherapy, curettage and electrodesiccation.[74]

Local destruction with liquid nitrogen (cryotherapy) is commonly applied.[97][98] This often results in a delayed formation of a vesicle or bulla. In patients with darker skins, cryotherapy may cause hypopigmentation in the long term.

Electrodessication and curettage is another common method but as with other destructive methods carries the risk of dyspigmentation and scarring.[99] The dermatologist curettes the clinically apparent tumour with a sharp round instrument, then coagulates the wound bed with electric current to dryness. The eschar is curetted twice more with subsequent electrodessication.

Laser therapy has been demonstrated to be an acceptable alternative to surgery for low-risk lesions on the trunk and extremities for patients with SCC.[100]

Photodynamic therapy, whereby a topical photosensitiser, such as 5-aminolevulinic acid or methyl aminolevulinic acid, induces protoporphyrin accumulation that results in cell death with exposure to visible light, is now widely used and compares well with other methods.[101]

Studies have shown that the efficacy of photodynamic therapy is similar to, or more effective than other traditional therapies, such as cryotherapy and electrodessication and curettage, with superior cosmetic outcomes.[101][102] Photodynamic therapy is an option for patients with tumours at sites where wound healing is poor/delayed, in the case of multiple and/or large tumours, and where surgery would be difficult or invasive.[103]

The treatment may result in peeling, crusting, or blistering, and hyperpigmentation may occur on darkly pigmented skin.

1st line – topical chemotherapy

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1st line –

topical chemotherapy

Topical chemotherapy with fluorouracil-based regimens (e.g., fluorouracil with or without calcipotriol) are preferred.[74]

Fluorouracil targets abnormal cells by providing high local concentrations of this chemotherapeutic agent without adverse systemic effects, and it has been demonstrated to have a significant clearance rate for SCC.[95][96] The advantage of this approach is that numerous lesions in an affected area are treated. In addition, treatment can be performed at home.

Responsive lesions will become erosive within a few days to weeks depending on the concentration of drug and frequency of application. After a crusted stage, the erosions re-epithelialise to leave cytologically normal skin.

Strict sun avoidance is highly recommended.

Primary options

fluorouracil topical: (5%) apply to the affected area(s) twice daily for 3-6 weeks

and

calcipotriol topical: (0.005%) apply to the affected area(s) once or twice daily for 3-6 weeks

2nd line – standard clinical excision or Mohs surgery

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2nd line –

standard clinical excision or Mohs surgery

Patients with squamous cell carcinoma (SCC) in situ should be followed closely, and tumours that do not respond or recur should be excised.

Standard clinical excision is a common therapeutic option for SCC. For the primary treatment of low-risk SCC >2 cm in diameter, 6-mm clinical margins are recommended in the US.[74] UK guidelines recommend excision with a clinical peripheral surgical margin of ≥4 mm for low-risk cutaneous SCC tumour.[90]

Mohs micrographic surgery is a primary treatment option for low-risk SCC.[74] It may be used for tumours on cosmetically sensitive areas (e.g., face, ears, nose, lips, neck and hands), tumours >2 cm in diameter, and all recurrent tumours, and should be performed by dermatological surgeons who have specialised training and experience in this procedure.[74]

Tumour diameter, thickness, perineural invasion, and patient factors determine degree of tumour risk.[74][90]

In the UK, ≥1 mm histological clearance of SCC excision from all margins is recommended.[90] This is achieved by excising sufficient peripheral and deep tissues. For mobile lesions, the deep margin should be within the next clear surgical plane. For deeply infiltrating lesions at any site, achieving a clear/uninvolved deep margin may require excision of fascia, muscle, bone, or underlying structures. Where possible, uninvolved margins should be confirmed histologically.[90]

Mohs surgery provides the highest cure rate for SCC, at >97% for primary tumours. In addition, it allows for optimal tissue sparing, as only the additional areas that carry tumours are removed.[109][110] Local recurrence rates following Mohs has been reported at 16%, with rates of nodal metastasis at 3% for patients with verrucous carcinoma.[111]

In 2012, the American Academy of Dermatology, the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery published appropriate use criteria for Mohs micrographic surgery, which detail specific indications for performing Mohs surgery.[112]

Consider – radiotherapy

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Consider –

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Referral to a radiation oncologist for adjuvant radiotherapy may be indicated for aggressive tumour subtypes.[105][106]

Adjuvant radiotherapy may be indicated for patients with positive or negative margins.[74] However it is contraindicated if the patient has genetic conditions predisposing to skin cancer (e.g. basal cell nevus syndrome), and not advisable for patients with with connective tissue diseases such as scleroderma.[74]

2nd line – radiotherapy

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2nd line –

radiotherapy

Radiotherapy is an option for treatment of SCC in situ (Bowen's disease), particularly those cases that are deemed unresectable or in patients who are poor surgical candidates. A high rate of tumour control, with minimal morbidity and preservation of normal tissues, has been demonstrated.[104]

However it is contraindicated if the patient has genetic conditions predisposing to skin cancer (e.g. basal nevus syndrome), and not advisable for patients with with connective tissue diseases such as scleroderma.[74]

invasive SCC

non-cosmetically sensitive locations or <2 cm in diameter

1st line – standard clinical excision or electrodessication and curettage or shave excision

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1st line –

standard clinical excision or electrodessication and curettage or shave excision

Invasive SCC is stratified into low-risk, high-risk, or very-high-risk SCC for local recurrence, metastases, or death from disease.[74] Treatment differs based on this stratification.[74] Tumour diameter, thickness, perineural invasion, and patient factors determine degree of tumour risk.[74][90]

Patients with low-risk SCC with tumours in non-cosmetically sensitive locations may be treated with electrodessication and curettage, shave removal, or standard clinical excision.[74] For patients with high- or very-high-risk SCC, where surgery or radiotherapy has a high likelihood of cure, standard clinical excision is the primary treatment for patients with tumours in non-cosmetically sensitive locations.[74]

The 5-year cure rate with standard excision for primary SCC is 92%, for recurrent SCC the cure rate is 77%.[108] When performing surgery, peripheral tumour margins should be determined under a bright light with magnification or dermoscopy.

UK guidelines recommend excision with a clinical peripheral surgical margin of ≥4 mm, ≥6 mm, or ≥10 mm for low-risk, high-risk, or very-high-risk cutaneous SCC tumour, respectively.[90] In the US, standard excision with a 4- to 6-mm clinical margin is recommended for local low-risk cutaneous SCC; wider surgical margin, with intraoperative margin control, and post-operative margin assessment, is required for high-risk tumours.[74][88]

Shave removal is an option for some low-risk SCCs. It is most suitable for dermal and epidermal lesions.[74] The tumour is removed by making a transverse cut with a scalpel underneath the lesion.[107]

Electrodessication and curettage is another option for treatment of some low-risk SCCs, but it may cause dyspigmentation and scarring.[99] The dermatologist curettes the clinically apparent tumour with a sharp round instrument, then coagulates the wound bed with electric current to dryness. The eschar is curetted twice more with subsequent electrodessication.

Consider – radiotherapy

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Consider –

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Referral to a radiation oncologist for adjuvant radiotherapy may be indicated for aggressive tumour subtypes.[105][106]

Adjuvant radiotherapy may be indicated for patients with positive or negative margins.[74] However it is contraindicated if the patient has genetic conditions predisposing to skin cancer (e.g. basal nevus syndrome), and not advisable for patients with with connective tissue diseases such as scleroderma.[74]

cosmetically sensitive locations or >2 cm in diameter

1st line – Mohs surgery

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1st line –

Mohs surgery

Mohs micrographic surgery is the primary treatment option for any risk level of SCC when the tumours are on cosmetically sensitive areas (e.g., face, ears, nose, lips, neck and hands), tumours are >2 cm in diameter, and also for all recurrent tumours. Mohs surgery should be performed by dermatologic surgeons who have specialised training and experience in this procedure.[74]

Mohs surgery provides the highest cure rate for squamous cell carcinoma, at >97% for primary tumours. In addition, it allows for optimal tissue sparing, as only the additional areas that carry tumours are removed.[109][110] Local recurrence rates following Mohs has been reported at 16%, with rates of nodal metastasis at 3% for patients with verrucous carcinoma.[111]

Consider – radiotherapy

Back

Consider –

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Referral to a radiation oncologist for adjuvant radiotherapy may be indicated for aggressive tumour subtypes.[105][106]

Adjuvant radiotherapy may be indicated for patients with positive or negative margins.[74] However it is contraindicated if the patient has genetic conditions predisposing to skin cancer (e.g. basal nevus syndrome), and not advisable for patients with with connective tissue diseases such as scleroderma.[74]

2nd line – radiotherapy

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2nd line –

radiotherapy

For non-surgical candidates, definitive radiotherapy may be considered after discussion with a multi-disciplinary team.[74] However it is contraindicated if the patient has genetic conditions predisposing to skin cancer (e.g. basal cell nevus syndrome), and not advisable for patients with with connective tissue diseases such as scleroderma.[74]

locally advanced SCC

non-cosmetically sensitive locations or <2 cm in diameter

1st line – standard clinical excision

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1st line –

standard clinical excision

For patients with locally advanced SCC with tumours on non-cosmically sensitive locations, standard clinical excision with wider surgical margins and post-operative assessment is recommended as the primary treatment.[74]

UK guidelines recommend excision with a clinical peripheral surgical margin of ≥4 mm, ≥6 mm, or ≥10 mm, for low-risk, high-risk, or very-high-risk cutaneous SCC tumour, respectively.[90] In the US, standard excision with a 6-mm clinical margin is recommended for local low-risk cutaneous SCC; wider surgical margin, with intraoperative margin control, and post-operative margin assessment, is required for high-risk tumours.[74][88] Tumour diameter, thickness, perineural invasion, and patient factors determine degree of tumour risk.[74][90]

Consider – neoadjuvant cemiplimab

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Consider –

neoadjuvant cemiplimab

Additional treatment recommended for SOME patients in selected patient group

Neoadjuvant treatment with cemiplimab, a human monoclonal antibody targeting programmed death receptor-1 (PD-1) on T cells, should be considered for patients with locally advanced SCC if the tumour is growing rapidly, is in-transit metastasis, lymphovascular invasion, or is borderline resectable.[74]

Early phase trials have demonstrated promising results for patients with SCC treated with neoadjuvant cemiplimab.[117][118][119]

See local specialist protocol for dosing guidelines.

Primary options

cemiplimab

Consider – clinical trial

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Consider –

clinical trial

Additional treatment recommended for SOME patients in selected patient group

Entry into a clinical trial can be considered for patients with locally advanced SCC for both surgical and non-surgical candidates after a discussion with a multidisciplinary team.[74]

1st line – radiotherapy and/or systemic therapy

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1st line –

radiotherapy and/or systemic therapy

For patients with locally advanced SCC who are non-surgical candidates (due to comorbidities, extent of disease, risk of functional or cosmetic defects, or the inability to clear disease with surgery), treatment options include radiotherapy with or without systemic therapy, or systemic therapy alone.[74]

For non-surgical candidates, definitive radiotherapy may be considered after discussion with a multidisciplinary team.[74] However radiotherapy is contraindicated if the patient has genetic conditions predisposing to skin cancer (e.g. basal nevus syndrome), and not advisable for patients with with connective tissue diseases such as scleroderma.[74]

If systemic therapy is given in combination with radiotherapy, cisplatin is the preferred option.[74]

If systemic therapy is given alone, preferred regimens include an anti-programmed cell death-1 (PD-1) monoclonal antibody, such as cemiplimab or pembrolizumab.[74] One retrospective, observational, multi-centre study reported that real-world data confirmed the efficacy and safety of cemiplimab for patients with advanced SCC, but that efficacy may differ slightly between European and US regions, which may be associated with different genetic backgrounds.[113] In Europe and the UK, only cemiplimab is approved for this indication.[114][115]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

cemiplimab

pembrolizumab

Consider – clinical trial

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Consider –

clinical trial

Additional treatment recommended for SOME patients in selected patient group

Entry into a clinical trial can be considered for patients with locally advanced SCC for both surgical and non-surgical candidates after a discussion with a multidisciplinary team.[74]

cosmetically sensitive locations or >2 cm in diameter

1st line – Mohs surgery

Back

1st line –

Mohs surgery

For patients with locally advanced SCC with tumours on cosmically sensitive locations (e.g face, ears, nose, lips, neck and hands), Mohs surgery with wider surgical margins and post-operative assessment is recommended as the primary treatment.[74]

Mohs surgery should be performed by dermatological surgeons who have specialised training and experience in this procedure.[74]

Mohs surgery provides the highest cure rate for SCC, at >97% for primary tumours. In addition, it allows for optimal tissue sparing, as only the additional areas that carry tumours are removed.[109][110] Local recurrence rates following Mohs have been reported at 16%, with rates of nodal metastasis at 3% for patients with verrucous carcinoma.[111]

Consider – neoadjuvant cemiplimab

Back

Consider –

neoadjuvant cemiplimab

Additional treatment recommended for SOME patients in selected patient group

Early phase trials have demonstrated promising results for patients with SCC treated with neoadjuvant cemiplimab.[117][118][119]

See local specialist protocol for dosing guidelines.

Primary options

cemiplimab

Consider – clinical trial

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Consider –

clinical trial

Additional treatment recommended for SOME patients in selected patient group

Entry into a clinical trial can be considered for patients with locally advanced SCC for both surgical and non-surgical candidates after a discussion with a multidisciplinary team.[74]

1st line – radiotherapy and/or systemic therapy

Back

1st line –

radiotherapy and/or systemic therapy

For non-surgical candidates, definitive radiotherapy may be considered after discussion with a multidisciplinary team.[74] However, radiotherapy is contraindicated if the patient has genetic conditions predisposing to skin cancer (e.g., basal nevus syndrome), and not advisable for patients with with connective tissue diseases such as scleroderma.[74]

If systemic therapy is given in combination with radiotherapy, cisplatin is the preferred option.[74]

See local specialist protocol for dosing guidelines.

Primary options

cisplatin

cemiplimab

pembrolizumab

Consider – clinical trial

Back

Consider –

clinical trial

Additional treatment recommended for SOME patients in selected patient group

Entry into a clinical trial can be considered for patients with locally advanced SCC for both surgical and non-surgical candidates after a discussion with a multidisciplinary team.[74]

ONGOING

immunocompromised or high risk of metastatic disease

1st line – oral retinoid

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1st line –

oral retinoid

Oral retinoids have been shown to prevent recurrence and progression, particularly in immunosuppressed patients (e.g., AIDS, solid organ transplant recipients), and also in patients with early-onset high-risk (i.e., large and invasive) tumours, high sun exposure, and lightly pigmented skin.[42][116]

Primary options

acitretin: 25-50 mg orally once daily for 9-12 months

isotretinoin: 0.5 to 1 mg/kg/day orally for 9-12 months

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Squamous cell carcinoma of the skin

Treatment algorithm

SCC in situ (Bowen's disease)

destructive therapies

topical chemotherapy

Primary options

standard clinical excision or Mohs surgery

radiotherapy

radiotherapy

invasive SCC

standard clinical excision or electrodessication and curettage or shave excision

radiotherapy

Mohs surgery

radiotherapy

radiotherapy

locally advanced SCC

standard clinical excision

neoadjuvant cemiplimab

Primary options

clinical trial

radiotherapy and/or systemic therapy

Primary options

clinical trial

Mohs surgery

neoadjuvant cemiplimab

Primary options

clinical trial

radiotherapy and/or systemic therapy

Primary options

clinical trial

immunocompromised or high risk of metastatic disease

oral retinoid

Primary options