Treatment algorithm

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

INITIAL

nevoid basal cell carcinoma (Gorlin-Goltz) syndrome

1st line – treatment of BCCs

Back
INITIAL
|
nevoid basal cell carcinoma (Gorlin-Goltz) syndrome
1st line – 

treatment of BCCs

Treat any coexisting basal cell carcinomas (BCCs) with conventional therapy.

Choice of treatment is dictated by the lesion size, location, number, subtype, depth of invasion, and tissue margin (if biopsied).[42][44]

Strict sun protection measures and frequent skin checks are recommended for people with nevoid basal cell carcinoma syndrome.

1st line – hedgehog pathway inhibitor + treatment of BCCs

Back
INITIAL
|
nevoid basal cell carcinoma (Gorlin-Goltz) syndrome
1st line – 

hedgehog pathway inhibitor + treatment of BCCs

The hedgehog pathway inhibitors vismodegib and sonidegib may be considered for the management of nevoid basal cell carcinoma syndrome (NBCCS), but they are not approved by the US Food and Drug Administration (FDA) for this indication.[42]​​[60][61]

Treatment is under a specialist team.

Treat any coexisting basal cell carcinomas (BCCs) with conventional therapy.

Strict sun protection measures and frequent skin checks are recommended for people with NBCCS.

Primary options

vismodegib: consult specialist for guidance on dose

OR

sonidegib: consult specialist for guidance on dose

ACUTE

low-risk subtype in non-cosmetically challenging location

1st line – conventional surgery

Back
ACUTE
|
low-risk subtype in non-cosmetically challenging location
|
surgery acceptable to patient
1st line – 

conventional surgery

Standard excision is a first-line treatment for patients with low-risk basal cell carcinoma (BCC).[42][45]​​​[47]

BCC, regardless of the histological growth pattern, is characterised by asymmetrical subclinical extension beyond the clinically visible tumour. To ensure complete removal with histologically negative margins, standard excision must include a margin of clinically normal-appearing skin.[47][63]​ Excision with 4 mm clinical margins should result in complete removal in more than 95% of cases.[44][64]​ Five-year recurrence rates are typically ≤5% following standard surgical excision, pending histological subtype.[59]

Care should be taken (by a pathologist) to ink all of the margins of the excisional specimen, and to evaluate for the presence of characteristic stroma of BCC at the tissue edges (margins). If such a stroma is seen at the margin, recurrence is still a possibility, as superficial components of BCC may exhibit so-called skip areas in the biopsy specimen.

Adverse effects include wound dehiscence and excessive scarring, as well as infections. Most of the adverse effects are relatively minor and can be relieved with drugs if needed.[62]

1st line – curettage ± electrodesiccation and biopsy

Back
ACUTE
|
low-risk subtype in non-cosmetically challenging location
|
surgery acceptable to patient
1st line – 

curettage ± electrodesiccation and biopsy

A treatment option for selected low-risk lesions with three caveats; curettage and electrodesiccation should not be used to treat areas with terminal hair growth such as the scalp, pubic and axillary regions, or beard area due to the risk that a tumour extending down follicular structures might not be adequately removed; if the subcutaneous layer is reached during the course of curettage and electrodesiccation, then surgical removal should be performed instead. The effectiveness of this technique is determined by the ability of the clinician to distinguish between firm, normal dermis, and soft tumour tissue. As the subcutaneous adipose is softer than tumour tissue, the ability to completely remove tumour cells is diminished; if curettage and electrodesiccation is performed based on the appearance of a low-risk tumour, biopsy results of the tissue taken at the time of C&E should be reviewed to make sure that there are no high-risk pathological features that would require additional therapy.[42][44][45]​​[47]

The usual standard is curettage followed by electrodesiccation for up to three cycles.[42]

​ Outcomes are highly operator dependent and the procedure should be performed by an experienced practitioner.

1st line – shave removal

Back
ACUTE
|
low-risk subtype in non-cosmetically challenging location
|
surgery acceptable to patient
1st line – 

shave removal

Shave removal is an option for low-risk basal cell carcinoma of the trunk or extremities and in situations where additional treatment would pose morbidity or hardship.[44] The tumour is excised by making a transverse, bowl-shaped cut with a scalpel underneath the lesion.[65]

1st line – cryosurgery or non-surgical topical therapies or radiotherapy

Back
ACUTE
|
low-risk subtype in non-cosmetically challenging location
|
superficial BCC - patient unsuitable for surgery
1st line – 

cryosurgery or non-surgical topical therapies or radiotherapy

There are a number of alternatives for patients with superficial basal cell carcinoma (BCC) who are keen to avoid, or are unsuitable for, conventional surgery or curettage followed by electrodesiccation.[42][44][47]

Radiotherapy may be considered for patients (including those with recurrent disease) who are not amenable to surgery, or for patients who may not tolerate surgery due to comorbidities or frailty (e.g., for an older adult with basal cell carcinoma [BCC] on the nasolabial fold).[42][44][47]​ The appropriateness of radiotherapy should be determined in consultation with a radiation oncologist.[44]

Radiotherapy for recurrent BCC previously treated with radiotherapy is not recommended.[42][44]

Cosmesis is inferior to surgery, and the cure rate with radiotherapy may be lower.[47][59]​ Recurrence rates (3-5 years) of <10% have been reported for primary and recurrent disease treated with radiotherapy.[59][80][81] 

Radiotherapy has well-known complications; for example, permanent hair loss, radiation burn, and increased risk of secondary cancers.[6]​ Radiotherapy is contraindicated in patients with genetic conditions that predispose to skin cancer (e.g., nevoid basal cell carcinoma syndrome).[44]

Cryosurgery has been used for a long time for the treatment of BCC, and it has been demonstrated to be effective for superficial variants. Reported recurrence rates of BCC with cryotherapy range from 0% to 13% for patients with primary BCC.[44][46] Disadvantages include scarring, difficulty in assessing recurrence and lack of tissue diagnosis or proof of tumour clearance.[46]

Evidence suggests that imiquimod is effective for treating nodular and superficial BCC.[67]​ A phase 3 randomised trial in patients with superficial or nodular BCC showed that imiquimod provided an 84% clinical success rate at 3 years, and 82.5% at 5 years.[68][69]​​​ There is some evidence to suggest that recurrence rates in patients treated with topical imiquimod may be associated with tumour thickness.[70] Of the non-surgical options, imiquimod has the best evidence to support its efficacy.[59]​ Evidence indicates that imiquimod probably leads to fewer recurrences than methyl aminolevulinate photodynamic therapy (MAL-PDT); there is probably little to no difference between these treatments in terms of observer‐rated good/excellent cosmetic outcomes. [ Cochrane Clinical Answers logo ] ​ Rarely, with imiquimod, systemic reactions occur and include flu-like symptoms, arthralgia, myalgia, fatigue, and lymphadenopathy.[6]

Topical fluorouracil has been demonstrated to be effective for the treatment of superficial BCC, cure rates of up to 90%, and 5 year survival probability of 70% have been reported.[6][71][72] This treatment is useful for multiple, low-risk lesions on the head and neck, torso and legs, and should be administered by a dermatologist due to potential complications. Application site reactions are common, dose-dependent, and include pruritus, erythema, oedema, pain, hyperpigmentation, hypopigmentation, bleeding, crusting, and erosions.[6]

Phototherapy is another option for superficial low-risk BCC. Results from systematic reviews have shown that rates of excellent or good cosmetic outcomes are higher with phototherapy compared with surgery.[59][73][74][75]​​​​ Cure rates ranging from 60% to 100% have been reported for phototherapy, mainly for patients with superficial or nodular disease.[73][76][77][78]​​​​

Local adverse effects such as itching, erythema, and weeping are reported with topical therapies for BCC.[59][63][66]

Primary options

imiquimod topical: (5%) apply to the affected area(s) five times weekly for 6 weeks

OR

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

low-risk subtype in cosmetically challenging location

1st line – Mohs surgery or other form of peripheral and deep en face margin assessment (PDEMA)

Back
ACUTE
|
low-risk subtype in cosmetically challenging location
1st line – 

Mohs surgery or other form of peripheral and deep en face margin assessment (PDEMA)

Mohs surgery is a variant of dermatological surgery in which the practitioner examines margins via intraoperative consultation (ex tempore, frozen section) while the patient's site of procedure is still open.

It is a tissue-sparing technique that is often utilised in the facial and other cosmetically sensitive regions; scars are smaller than those of conventional surgery, and tissue defects are easier to repair.[52] Recurrence rates with Mohs surgery are very low (2% to 5%).[42][79]

Mohs is the most common form of PDEMA. Other forms of PDEMA involve a team approach where a separate pathologist interprets the histological margins for the surgeon. PDEMA methods that use permanent section analysis or intraoperative frozen section analysis are an acceptable alternative to Mohs but must include a complete assessment of all deep and peripheral margins.[44]

Adverse effects can include wound dehiscence, excessive scarring, and infections.

Most of the adverse effects are relatively minor and can be addressed with drugs if needed.[62]

high-risk subtype

1st line – Mohs surgery or other form of peripheral and deep en face margin assessment (PDEMA)

Back
ACUTE
|
high-risk subtype
1st line – 

Mohs surgery or other form of peripheral and deep en face margin assessment (PDEMA)

Resection with PDEMA is the preferred treatment for high-risk basal cell carcinoma (BCC).[42][44][46]

Mohs surgery is the most common form of PDEMA. Mohs surgery is a variant of dermatological surgery in which the practitioner examines margins via intraoperative consultation (ex tempore, frozen section) while the patient's site of procedure is still open.

It is a tissue-sparing technique that is often utilised in the facial and other cosmetically sensitive regions; scars are smaller than those of conventional surgery, and tissue defects are easier to repair.[52]

Recurrence rates with Mohs surgery are very low (2% to 5%).[42][79]​

Other forms of PDEMA involve a team approach where a separate pathologist interprets the histological margins for the surgeon. PDEMA methods that use permanent section analysis or intraoperative frozen section analysis are an acceptable alternative to Mohs but must include a complete assessment of all deep and peripheral margins.[44]

Adverse effects can include wound dehiscence, excessive scarring, and infections.

Most of the adverse effects are relatively minor and can be addressed with drugs if needed.[62]

Multidisciplinary consultation at a centre with specialised expertise is recommended for patients with high-risk disease.[44]

2nd line – conventional surgery

Back
ACUTE
|
high-risk subtype
2nd line – 

conventional surgery

Standard excision may be considered for select patients with high-risk tumours.[44][47]

Basal cell carcinoma (BCC), regardless of the histological growth pattern, is characterised by asymmetric subclinical extension beyond the clinically visible tumour. To ensure complete removal with histologically negative margins, standard excision must include a margin of clinically normal-appearing skin.[47][63]​ Wider margins are recommended for high-risk disease.[44] Care should be taken (by a pathologist) to ink all of the margins of the excisional specimen, and to evaluate for presence of the characteristic stroma of BCC at the tissue edges (margins). If such a stroma is seen at the margin, recurrence is still a possibility, as superficial components of BCC may exhibit so-called skip areas in the biopsy specimen.

Adverse effects include wound dehiscence and excessive scarring, as well as infections. Most of the adverse effects are relatively minor and can be relieved with drugs if needed.[62]

Multidisciplinary consultation at a centre with specialised expertise is recommended for patients with high-risk disease.[44]

3rd line – curettage ± electrodesiccation or shave removal

Back
ACUTE
|
high-risk subtype
3rd line – 

curettage ± electrodesiccation or shave removal

Most guidelines recommend against curettage and electrodesiccation for treatment of high-risk basal cell carcinoma (BCC) because of unacceptably high recurrence rates.[6][46][47]​​

However, the National Comprehensive Cancer Network (NCCN) guideline suggests that curettage and electrodesiccation or shave removal may be considered as an alternative treatment option for high-risk BCCs in select circumstances if Mohs, resection with PDEMA, and standard excision are difficult to perform due to patient comorbidities (e.g., thrombocytopenia, immunosuppression, bleeding, diathesis, multiple primary BCCs).[44] This should be reserved for clinically diagnosed non-facial BCCs <6 mm in depth on the head, neck, hands, feet, pretibial, or anogenital area that are clinically confined to the dermis.[44]

Outcomes for curettage and electrodessication are highly operator dependent, and the procedure should be performed by an experienced practitioner.

Guidelines advise strong caution when selecting a treatment modality for high-risk BCC that does not include complete margin assessment.[44][47]​ Multidisciplinary consultation at a centre with specialised expertise is recommended for patients with high-risk disease.[44]

ONGOING

positive margins on initial procedure

1st line – Mohs surgery or other form of peripheral and deep en face margin assessment (PDEMA)

Back
ONGOING
|
positive margins on initial procedure
1st line – 

Mohs surgery or other form of peripheral and deep en face margin assessment (PDEMA)

Resection with PDEMA is the preferred treatment for high-risk basal cell carcinoma (BCC) and for excision of low-risk BCC after positive margins with standard excision.[42][44][46]​​

Mohs surgery is the most common form of PDEMA. Mohs surgery is a variant of dermatological surgery in which the practitioner examines margins via intraoperative consultation (ex tempore, frozen section) while the patient's site of procedure is still open.

It is a tissue-sparing technique that is often utilised in the facial and other cosmetically sensitive regions; scars are smaller than those of conventional surgery, and tissue defects are easier to repair.[52]

Recurrence rates with Mohs surgery are very low (2% to 5%).[42][79]

Other forms of PDEMA involve a team approach where a separate pathologist interprets the histological margins for the surgeon. PDEMA methods that use permanent section analysis or intraoperative frozen section analysis are an acceptable alternative to Mohs but must include a complete assessment of all deep and peripheral margins.[44]

Adverse effects can include wound dehiscence, excessive scarring, and infections. Most of the adverse effects are relatively minor and can be addressed with drugs if needed.[62]

2nd line – re-excision

Back
ONGOING
|
positive margins on initial procedure
2nd line – 

re-excision

If Mohs surgery or another form of peripheral and deep en face margin assessment (PDEMA) is not available, re-excision of margins in a further procedure should ensure clearance.

complicated BCC recurrences and/or site not accessible to surgical and topical therapies

1st line – radiotherapy or hedgehog pathway inhibitor

Back
ONGOING
|
complicated BCC recurrences and/or site not accessible to surgical and topical therapies
1st line – 

radiotherapy or hedgehog pathway inhibitor

Radiotherapy may be considered for patients (including those with recurrent disease) who are not amenable to surgery or for patients who may not tolerate surgery due to comorbidities or frailty (e.g., for an older adult with basal cell carcinoma [BCC] on the nasolabial fold).[42][44][47]

The appropriateness of radiotherapy should be determined in consultation with a radiation oncologist.[44]​ Radiotherapy for recurrent BCC previously treated with radiotherapy is not recommended.[42][44]

Cosmesis is inferior to surgery, and the cure rate with radiotherapy may be lower.[47][59] Recurrence rates (3-5 years) of <10% have been reported for primary and recurrent disease treated with radiotherapy.[59][80][81]

Radiotherapy has well-known complications; for example, permanent hair loss, radiation burn and increased risk of secondary cancers.[6]​ Radiotherapy is contraindicated in patients with genetic conditions that predispose to skin cancer (e.g., nevoid basal cell carcinoma syndrome).[44]

The oral hedgehog pathway inhibitors sonidegib and vismodegib are approved by the US Food and Drug Administration (FDA) for the treatment of recurrent disease. Frequently hedgehog pathway inhibitors are associated with serious adverse effects such as muscle spasms, alopecia, taste loss, weight loss, decreased appetite, fatigue, nausea, and diarrhoea. Drug holidays or other alternatives to daily dosing can be used to improve adherence to therapy and quality of life.[44]

Primary options

sonidegib: consult specialist for guidance on dose

OR

vismodegib: consult specialist for guidance on dose

advanced disease

1st line – surgery ± neoadjuvant vismodegib or cemiplimab

Back
ONGOING
|
advanced disease
|
locally advanced disease
1st line – 

surgery ± neoadjuvant vismodegib or cemiplimab

Surgery (with or without neoadjuvant systemic therapy) is recommended as an option for patients with locally advanced disease.[44] Neoadjuvant systemic therapy may be considered to downstage tumours prior to surgery.[44]

Resection with peripheral and deep en face margin assessment (PDEMA) is the preferred method of excision for advanced disease (primary or recurrent).[44] Mohs surgery is the most common form of PDEMA. PDEMA methods that use permanent section analysis or intraoperative frozen section analysis are an acceptable alternative to Mohs but must include a complete assessment of all deep and peripheral margins.[44] If Mohs or other form of PDEMA is not available, standard excision may be considered.[44]

However, surgery for advanced disease can be limited by the difficulty of achieving complete removal without significant morbidity and functional impairment.[45][83]​ The suitability of surgery and surgical technique should be discussed with a multidisciplinary team.[44][45]​ Adverse effects of excision include wound dehiscence and excessive scarring, as well as infections. Most of the adverse effects are relatively minor and can be relieved with drugs if needed.[62]

Vismodegib (an oral hedgehog pathway inhibitor) is recommended as a neoadjuvant treatment for patients with locally advanced basal cell carcinoma (BCC).[44] One open-label, phase 2 non-comparative study demonstrated that neoadjuvant vismodegib allows for downstaging of surgical procedures in patients with locally advanced BCC in functionally sensitive locations.[84]

Cemiplimab, a recombinant human immunoglobulin G4 monoclonal antibody that binds to programmed death receptor-1 (PD-1), may be used as neoadjuvant treatment when vismodegib is not appropriate or for patients previously treated with a hedgehog pathway inhibitor.[44]

Primary options

vismodegib: consult specialist for guidance on dose

Secondary options

cemiplimab: consult specialist for guidance on dose

Consider – radiotherapy

Back
ONGOING
|
advanced disease
|
locally advanced disease
Consider – 

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Radiotherapy may be used as an adjuvant treatment for patients with positive margins after resection or nerve invasion.[44]

Radiotherapy has well-known complications; for example, permanent hair loss, radiation burn, and increased risk of secondary cancers.[6]​ Radiotherapy is contraindicated in patients with genetic conditions that predispose to skin cancer (e.g., nevoid basal cell carcinoma syndrome).[44]

2nd line – radiotherapy

Back
ONGOING
|
advanced disease
|
locally advanced disease
2nd line – 

radiotherapy

Radiotherapy is a suitable alternative to surgery when either the patient or the tumours are not amenable to surgery due to functional or cosmetic concerns, the patient's general health, or patient preference.[85][86]​ The feasibility of radiotherapy for advanced disease should be determined in consultation with a radiation oncologist.[44]

Radiotherapy has well-known complications; for example, permanent hair loss, radiation burn, and increased risk of secondary cancers.[6]​ Radiotherapy is contraindicated in patients with genetic conditions that predispose to skin cancer (e.g., nevoid basal cell carcinoma syndrome).[44]

3rd line – hedgehog pathway inhibitor or cemiplimab

Back
ONGOING
|
advanced disease
|
locally advanced disease
3rd line – 

hedgehog pathway inhibitor or cemiplimab

For patients who experience recurrence following surgery, or who are not candidates for surgery or radiotherapy, the hedgehog pathway inhibitors vismodegib and sonidegib are recommended as potential treatments for locally advanced basal cell carcinoma (BCC).[44][45]​ The National Comprehensive Cancer Network (NCCN) recommends systemic therapy for patients with locally advanced disease if surgery and/or radiotherapy are not feasible.[44] Frequently, hedgehog pathway inhibitors are associated with serious adverse effects such as muscle spasms, alopecia, taste loss, weight loss, decreased appetite, fatigue, nausea, and diarrhoea. Drug holidays or other alternatives to daily dosing can be used to improve adherence to therapy and quality of life.[44]

In the ERIVANCE study, investigator-assessed objective response rates among patients treated with vismodegib for locally advanced BCC and metastatic BCC were 60.3% and 48.5%, respectively.[88]​ Median overall survival and progression‐free survival for patients with metastatic BCC treated with vismodegib were 33.4 months and 9.3 months, respectively.[88] In another open-label study, median progression-free survival of vismodegib-treated patients with metastatic BCC was 13.1 months.[89]​ With 30 months of follow-up, a randomised double-blind study of sonidegib in patients with locally advanced and metastatic BCC reported central (blinded independent) objective response rates of 56.1% in locally advanced BCC and 7.7% in metastatic BCC.[90]​ A median progression-free survival of 13.1 months was reported among patients with metastatic BCC.[90]

Cemiplimab, a recombinant human immunoglobulin G4 monoclonal antibody that binds to programmed death receptor-1 (PD-1), is recommended for patients with locally advanced disease who have previously been treated with, or are intolerant to, hedgehog pathway inhibitors.[44] One phase 2 open-label, multicentre, non-randomised trial of cemiplimab in patients with metastatic or locally advanced BCC, who had progressed on hedgehog pathway inhibitors or achieved no better than stable disease after 9 months, or were intolerant to hedgehog pathway inhibitor therapy, reported an objective response (independent central review) in 31% of patients (26 of 84; median duration of follow-up 15 months).[92]​ Serious treatment-emergent adverse events were reported in 29 patients (35%).[92]

Primary options

vismodegib: consult specialist for guidance on dose

OR

sonidegib: consult specialist for guidance on dose

Secondary options

cemiplimab: consult specialist for guidance on dose

Consider – radiotherapy

Back
ONGOING
|
advanced disease
|
locally advanced disease
Consider – 

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Radiotherapy may be combined with vismodegib in certain circumstances.[44] The appropriateness of radiotherapy should be determined in consultation with a radiation oncologist.[44]

In one small phase 2 trial of combined vismodegib and radiotherapy in patients with unresectable locally advanced basal cell carcinoma (BCC), the response rate was 63% (95% CI: 38% to 84%) after induction vismodegib and 83% (95% CI: 59% to 96%) after concurrent vismodegib and radiotherapy.[87]​ After 5 years, progression-free survival was 78% and overall survival was 83%.[87]

Data are insufficient to recommend radiotherapy combined with other systemic therapy options (sonidegib or cemiplimab) for unresectable locally advanced disease.

Radiotherapy has well-known complications; for example, permanent hair loss, radiation burn, and increased risk of secondary cancers.[6]​ Radiotherapy is contraindicated in patients with genetic conditions that predispose to skin cancer (e.g., nevoid basal cell carcinoma syndrome).[44]

1st line – surgery

Back
ONGOING
|
advanced disease
|
nodal disease
1st line – 

surgery

Surgery is recommended as an option for patients with nodal disease.[44] Resection with peripheral and deep en face margin assessment (PDEMA) is the preferred method of excision for advanced disease (primary or recurrent).[44] Mohs surgery is the most common form of PDEMA. If Mohs or other form of PDEMA is not available, standard excision may be considered.[44]

However, surgery for advanced disease can be limited by the difficulty of achieving complete removal without significant morbidity and functional impairment.[45][83] The suitability of surgery and surgical technique should be discussed with a multidisciplinary team.[44][45] 

Mohs surgery is a variant of dermatological surgery in which the practitioner examines margins via intraoperative consultation (ex tempore, frozen section) while the patient's site of procedure is still open. Mohs surgery is a tissue-sparing technique that is often utilised in the facial and other cosmetically sensitive regions; scars are smaller than those of conventional surgery, and tissue defects are easier to repair.[52]​ Recurrence rates with Mohs surgery are very low (2% to 5%).[42][79]

Other forms of PDEMA involve a team approach where a separate pathologist interprets the histological margins for the surgeon. PDEMA methods that use permanent section analysis or intraoperative frozen section analysis are an acceptable alternative to Mohs but must include a complete assessment of all deep and peripheral margins.[44]

BCC, regardless of the histological growth pattern, is characterised by asymmetric subclinical extension beyond the clinically visible tumour. To ensure complete removal with histologically negative margins, standard excision must include a margin of clinically normal-appearing skin.[47][63]

Care should be taken (by a pathologist) to ink all of the margins of the excisional specimen, and to evaluate for presence of the characteristic stroma of BCC at the tissue edges (margins). If such a stroma is seen at the margin, recurrence is still a possibility, as superficial components of BCC may exhibit so-called skip areas in the biopsy specimen.

Adverse effects of excision include wound dehiscence and excessive scarring, as well as infections. Most of the adverse effects are relatively minor and can be relieved with drugs if needed.[62]

Consider – radiotherapy

Back
ONGOING
|
advanced disease
|
nodal disease
Consider – 

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Radiotherapy may be used as an adjuvant treatment for patients with positive margins after resection or nerve invasion.[44]

Radiotherapy has well-known complications; for example, permanent hair loss, radiation burn, and increased risk of secondary cancers.[6]​ Radiotherapy is contraindicated in patients with genetic conditions that predispose to skin cancer (e.g., nevoid basal cell carcinoma syndrome).[44]

2nd line – radiotherapy

Back
ONGOING
|
advanced disease
|
nodal disease
2nd line – 

radiotherapy

The National Comprehensive Cancer Network (NCCN) recommends either radiotherapy or systemic therapy for patients with nodal disease if surgery is not feasible.[44]

​Radiotherapy is a suitable alternative to surgery when either the patient or the tumours are not amenable to surgery due to functional or cosmetic concerns, the patient's general health, or patient preference.[85][86]​ The National Comprehensive Cancer Network (NCCN) recommends either radiotherapy or systemic therapy for patients with nodal disease if surgery is not feasible.[44] The feasibility of radiotherapy for advanced disease should be determined in consultation with a radiation oncologist.[44]

Radiotherapy has well-known complications; for example, permanent hair loss, radiation burn, and increased risk of secondary cancers.[6]​ Radiotherapy is contraindicated in patients with genetic conditions that predispose to skin cancer (e.g., nevoid basal cell carcinoma syndrome).[44]

2nd line – hedgehog pathway inhibitor or cemiplimab

Back
ONGOING
|
advanced disease
|
nodal disease
2nd line – 

hedgehog pathway inhibitor or cemiplimab

The National Comprehensive Cancer Network (NCCN) recommends either systemic therapy or radiotherapy for patients with nodal disease if surgery is not feasible.[44]

For patients who experience recurrence following surgery, or who are not candidates for surgery or radiotherapy, the hedgehog pathway inhibitors vismodegib and sonidegib are recommended as potential treatments for nodal disease.[44][45]​  Frequently, hedgehog pathway inhibitors are associated with serious adverse effects such as muscle spasms, alopecia, taste loss, weight loss, decreased appetite, fatigue, nausea, and diarrhoea. Drug holidays or other alternatives to daily dosing can be used to improve adherence to therapy and quality of life.[44]

Cemiplimab, a recombinant human immunoglobulin G4 monoclonal antibody that binds to programmed death receptor-1 (PD-1), is recommended for patients with nodal disease who have previously been treated with, or are intolerant to, hedgehog pathway inhibitors.[44] One phase 2 open-label, multi-centre, non-randomised trial of cemiplimab in patients with metastatic or locally advanced basal cell carcinoma, who had progressed on hedgehog pathway inhibitors or achieved no better than stable disease after 9 months, or were intolerant to hedgehog pathway inhibitor therapy, reported an objective response (independent central review) in 31% of patients (26 of 84; median duration of follow-up 15 months).[92]​ Serious treatment-emergent adverse events were reported in 29 patients (35%).[92]

Primary options

vismodegib: consult specialist for guidance on dose

OR

sonidegib: consult specialist for guidance on dose

Secondary options

cemiplimab: consult specialist for guidance on dose

1st line – vismodegib or cemiplimab

Back
ONGOING
|
advanced disease
|
metastatic disease
1st line – 

vismodegib or cemiplimab

For patients who are not candidates for surgery or radiotherapy, the hedgehog pathway inhibitor vismodegib is recommended as the preferred systemic therapy option for metastatic disease.[44] Frequently, hedgehog pathway inhibitors are associated with serious adverse effects such as muscle spasms, alopecia, taste loss, weight loss, decreased appetite, fatigue, nausea, and diarrhoea. Drug holidays or other alternatives to daily dosing can be used to improve adherence to therapy and quality of life.[44]

Cemiplimab, a recombinant human immunoglobulin G4 monoclonal antibody that binds to programmed death receptor-1 (PD-1), is recommended for patients with metastatic disease who have previously been treated with, or are intolerant to, hedgehog pathway inhibitors.[44] One phase 2 open-label, multi-centre, non-randomised trial of cemiplimab in patients with metastatic or locally advanced basal cell carcinoma, who had progressed on hedgehog pathway inhibitors or achieved no better than stable disease after 9 months, or were intolerant to hedgehog pathway inhibitor therapy, reported an objective response (independent central review) in 31% of patients (26 of 84; median duration of follow-up 15 months).[92] Serious treatment-emergent adverse events were reported in 29 patients (35%).[92]

Primary options

vismodegib: consult specialist for guidance on dose

Secondary options

cemiplimab: consult specialist for guidance on dose

1st line – surgery (limited metastatic disease)

Back
ONGOING
|
advanced disease
|
metastatic disease
1st line – 

surgery (limited metastatic disease)

In highly selective circumstances, and with multidisciplinary consultation, resection of limited metastases can be considered.[44]

Resection with peripheral and deep en face margin assessment (PDEMA) is the preferred method of excision for advanced disease (primary or recurrent).[44] Mohs surgery is the most common form of PDEMA. If Mohs or other form of PDEMA is not available, standard excision may be considered.[44]

However, surgery for advanced disease can be limited by the difficulty of achieving complete removal without significant morbidity and functional impairment.[45][83]​ The suitability of surgery and surgical technique should be discussed with a multidisciplinary team.[44][45]

Mohs surgery is a variant of dermatological surgery in which the practitioner examines margins via intraoperative consultation (ex tempore, frozen section) while the patient's site of procedure is still open. Mohs surgery is a tissue-sparing technique that is often utilised in the facial and other cosmetically sensitive regions; scars are smaller than those of conventional surgery, and tissue defects are easier to repair.[52]​ Recurrence rates with Mohs surgery are very low (2% to 5%).[42][79]

Other forms of PDEMA involve a team approach where a separate pathologist interprets the histological margins for the surgeon. PDEMA methods that use permanent section analysis or intraoperative frozen section analysis are an acceptable alternative to Mohs but must include a complete assessment of all deep and peripheral margins.[44]

BCC, regardless of the histological growth pattern, is characterised by asymmetric subclinical extension beyond the clinically visible tumour. To ensure complete removal with histologically negative margins, standard excision must include a margin of clinically normal-appearing skin.[47][63]

Care should be taken (by a pathologist) to ink all of the margins of the excisional specimen, and to evaluate for presence of the characteristic stroma of BCC at the tissue edges (margins). If such a stroma is seen at the margin, recurrence is still a possibility, as superficial components of BCC may exhibit so-called skip areas in the biopsy specimen.

Adverse effects of excision include wound dehiscence and excessive scarring, as well as infections. Most of the adverse effects are relatively minor and can be relieved with drugs if needed.[62]

Consider – radiotherapy

Back
ONGOING
|
advanced disease
|
metastatic disease
Consider – 

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Radiotherapy may be used as an adjuvant treatment for patients with positive margins after resection or nerve invasion.[44]

Radiotherapy has well-known complications; for example, permanent hair loss, radiation burn, and increased risk of secondary cancers.[6]​ Radiotherapy is contraindicated in patients with genetic conditions that predispose to skin cancer (e.g., nevoid basal cell carcinoma syndrome).[44]

1st line – radiotherapy

Back
ONGOING
|
advanced disease
|
metastatic disease
1st line – 

radiotherapy

Radiotherapy is a suitable alternative to surgery for patients with limited metastatic disease when either the patient or the tumours are not amenable to surgery due to functional or cosmetic concerns, the patient's general health, or patient preference.[85][86]​ The feasibility of radiotherapy for advanced disease should be determined in consultation with a radiation oncologist.[44]

Radiotherapy has well-known complications; for example, permanent hair loss, radiation burn, and increased risk of secondary cancers.[6]​ Radiotherapy is contraindicated in patients with genetic conditions that predispose to skin cancer (e.g., nevoid basal cell carcinoma syndrome).[44]

1st line – best supportive care

Back
ONGOING
|
advanced disease
|
metastatic disease
1st line – 

best supportive care

Palliation and best supportive care is recommended for patients with metastatic disease when curative treatment is no longer appropriate.[44] Palliative care is specialised medical care for people with serious illness that focuses on achieving the best quality of life for both the patient and their family or carers. It provides patients with relief from the symptoms, pain, and the stress of a serious illness. (See Palliative care) 

back arrow

Choose a patient group to see our recommendations

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

Use of this content is subject to our disclaimer