Approach

Surgery remains the most effective treatment modality for basal cell carcinoma (BCC) in terms of reducing recurrence.​[42][44][46]​​​[48][59]​​​​ Surgery may be with standard excision, shave removal, curettage and electrodesiccation, or Mohs micrographic surgery (usually reserved for the face).​​[42][44]​​​[48]

Nonsurgical treatments are less effective, but the evidence suggests that recurrence rates are acceptable and they are important options to offer patients. Topical treatments are usually used for superficial BCC only, with nodular and morphoeic sub-types requiring surgery.​​[42][44][48]

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

Nevoid basal cell carcinoma (Gorlin-Goltz) syndrome

Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple BCCs, which often present at a young age.[32] A new diagnosis of a BCC in a child or teenager should prompt consideration of NBCCS.

Other elements associated with NBCCS are skin tags and cysts, jaw cysts, changes to bone, pits in the skin, fibromas, and medulloblastoma.[33]

Strict sun protection measures and frequent skin checks are recommended for people with NBCCS. In the early stages of NBCCS, BCCs will be managed with routine therapy. The hedgehog pathway inhibitors vismodegib and sonidegib may be considered for the management of NBCCS, but they are not approved by the Food and Drug Administration for this indication.[42]​​[60][61]

Low-risk subtype in noncosmetically challenging location: surgery

Standard excision is a first-line treatment for patients with low-risk BCC and may be considered for select patients with high-risk tumors.​[42][46][48]​​​ Adverse effects include wound dehiscence and excessive scarring, as well as infections. Most of the adverse effects are relatively minor and can be relieved by medication.[62]

BCC, regardless of the histologic growth pattern, is characterized by asymmetric subclinical extension beyond the clinically visible tumor. To ensure complete removal with histologically negative margins, standard excision must include a margin of clinically normal-appearing skin.[48][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 histologic subtype.[59]

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.

Curettage and electrodesiccation

A treatment option for selected low-risk lesions with three caveats:​[42][44][46][48]

  • 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 tumor 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 on the ability of the clinician to distinguish between firm, normal dermis, and soft tumor tissue. As the subcutaneous adipose is softer than tumor tissue, the ability to completely remove tumor cells is diminished.

  • If curettage and electrodesiccation is performed based on the appearance of a low-risk tumor, biopsy results of the tissue taken at the time of C&E should be reviewed to make sure that there are no high-risk pathologic features that would require additional therapy.

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

Curettage and electrodesiccation is not recommended for high-risk BCC because of unacceptably high recurrence rates.[6][47][48]​ Outcomes are highly operator dependent and the procedure should be performed by an experienced practitioner.

Shave removal

Shave removal is an option for low-risk BCC of the trunk or extremities.[44] The tumor is excised by making a transverse, bowl-shaped cut with a scalpel underneath the lesion.[65]

Low-risk subtype in noncosmetically challenging location: patient reluctant to undergo surgery

There are a number of alternatives for patients with superficial BCC who are keen to avoid, or are unsuitable for, conventional surgery, shave removal or curettage followed by electrodesiccation.[42][44][48]​ However, there is evidence that cure rates are approximately 10% lower with nonsurgical treatments.[44]

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

Radiation therapy

Radiation therapy is recommended for nonsurgical candidates, the appropriateness of radiation therapy should be determined with the advice of a radiation oncologist.[44]

Cryosurgery

Cryosurgery has been used for a long time for the treatment of BCC, and 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][47]​​ Disadvantages include scarring, difficulty in assessing recurrence and lack of tissue diagnosis or proof of tumor clearance.[47]

Topical imiquimod

Evidence suggests that imiquimod is effective for treating nodular and superficial BCC.[67]​ A phase 2 randomized 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 tumor thickness.[70]

Of the nonsurgical 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

Topical fluorouracil has been demonstrated to be effective for the treatment of superficial BCC. Cure rates of up to 90% have been reported, with a 70% probability of remaining tumor-free at 5 years.[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, edema, pain, hyperpigmentation, hypopigmentation, bleeding, crusting, and erosions.[6]

Phototherapy

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]​​​​​​

Cosmetically challenging location (head and neck) OR high-risk subtype OR positive margins on initial procedure

Mohs surgery is a variant of dermatologic 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 recommended for high-risk BCC (e.g., large morpheaform BCC, and BCC with poorly defined clinical margins) and for the excision of low-risk BCC after positive margins with standard excision.[42][44][47][49]

Mohs surgery is a tissue-sparing technique that is often utilized in the facial and other cosmetically sensitive regions; scars are smaller than those of conventional surgery, and tissue defects are easier to repair.[53] Recurrence rates with Mohs surgery are very low (2% to 5%).[42][79]

Mohs surgery is only available in larger centers; some health care providers are only able to offer standard excision. If Mohs surgery is not available, re-excision of margins in a further procedure should ensure clearance.

Sites not accessible to surgical and conventional topical therapies and complicated recurrences

Radiation therapy 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 BCC on the nasolabial fold).​[42][44][46][48]​​

The appropriateness of radiation therapy for patients with high-risk BCC who are nonsurgical candidates should be determined with the advice of a radiation oncologist.[44] A multidisciplinary consultation should be considered to discuss potential definitive radiation therapy.[44] Radiation therapy for recurrent BCC previously treated with radiation therapy is not recommended.[42][44]

Cosmesis is inferior to surgery, and the cure rate with radiation therapy may be lower.[48][59] Recurrence rates (3-5 years) of <10% have been reported for primary and recurrent disease treated with radiation therapy.[63][80][81]

Radiation therapy has well-known complications; for example, permanent hair loss, radiation burn, and increased risk of secondary cancers.[6]

The oral hedgehog pathway inhibitors sonidegib and vismodegib are approved by the Food And Drug Administration (FDA) for the treatment of recurrent disease. (See Advanced disease)

Advanced disease

Advanced BCC is defined as nodular or distant metastasis or as locally advanced BCC that is considered to be unresectable and not amenable to radiation therapy.[42][44][82]

Treatment for advanced disease should be discussed with a multidisciplinary team, and may include neoadjuvant treatment, Mohs surgery, standard excision, radiation therapy, or systemic therapy when surgery or radiation therapy are not feasible.[44] In highly selective circumstances, and with multidisciplinary consultation, resection of limited metastases can be considered.[44] (See Low-risk subtype for standard excision) (see Cosmetically challenging location for Moh’s)

Neoadjuvant treatment for advanced disease

Vismodegib (an oral hedgehog pathway inhibitor) is recommended as a neoadjuvant treatment for patients with locally advanced BCC.[44] Cemiplimab may be used as neoadjuvant treatment when vismodegib is not appropriate.[44] One open-label, phase 2 noncomparative study demonstrated that neoadjuvant vismodegib allows for downstaging of surgical procedures in patients with locally advanced BCC in functionally sensitive locations.[83]

Radiation therapy for advanced disease

Radiation therapy is a suitable alternative to surgery when either the patient or the tumors are not amenable to surgery due to functional or cosmetic concerns, the patient's general health, or patient preference.[84][85]​​ The feasibility of radiation therapy for advanced disease should be determined by a radiation oncologist.[44] Radiation therapy may be used as an adjuvant treatment for patients with positive margins after resection or nerve invasion.[44]

Systemic therapy for advanced disease: hedgehog pathway inhibitor

For patients who experience recurrence following surgery, or who are not candidates for surgery or radiation therapy, vismodegib or sonidegib (both oral hedgehog pathway inhibitors) are recommended as potential treatments for nodal, or locally advanced BCC.​[44][46] Vismodegib is recommended as a potential treatment for patients with metastatic BCC.[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 diarrhea. 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.[86] Median overall survival and progression‐free survival for patients with metastatic BCC treated with vismodegib were 33.4 months and 9.3 months, respectively.[86] In another open-label study, median progression-free survival of vismodegib-treated patients with metastatic BCC was 13.1 months.[87] 

With 30 months of follow-up, a randomized 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.[88] A median progression-free survival of 13.1 months was reported among patients with metastatic BCC.[88]

Systemic therapy for advanced disease: cemiplimab

Cemiplimab, a recombinant human immunoglobulin G4 monoclonal antibody that binds to programmed death receptor-1 (PD-1), is recommended for patients with recurrent locally advanced, nodal or distant metastases who have previously been treated with, or are intolerant to, hedgehog pathway inhibitors.​[44][46]

One phase 2 open-label, multicenter, nonrandomized 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).[89] Serious treatment-emergent adverse events were reported in 29 patients (35%).[89]

Palliation and 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 specialized medical care for people with serious illness that focuses on achieving the best quality of life for both the patient and their family or caregivers. It provides patients with relief from the symptoms, pain, and the stress of a serious illness. (See Palliative care)

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