The aim for treatment of BCC is to eradicate the tumour in a manner likely to result in a cosmetic outcome that is acceptable to the patient.3 For most BCC lesions the most effective treatment is excisional surgery, which offers the most prognostically reliable control rates with the advantage of a complete specimen for histological confirmation of tumour clearance,3,4 and low 5-year recurrence when complete excision is achieved.5,6 Surgery also delivers good cosmetic results, particularly when excision and wound repair are performed by experienced practitioners.3
Although surgical excision is often the most effective treatment for BCC there are other alternatives, including:
- curettage
- cryosurgery
- laser treatment
- surgical excision using various predetermined margins of control
- excision under frozen section control
- Mohs micrographic surgery
- radiotherapy
- topical treatment.
There is a lack of evidence comparing these different treatment modalities.7
Although field treatment for SK lesions on the face and scalp is not a PBS-subsidised indication, imiquimod is TGA approved and RPBS subsidised for this use. SK lesions may require treatment for cosmetic reasons or because of irritation or the potential for progression to cancer.4,8 No data are available assessing imiquimod as a therapy to prevent squamous cell carcinoma (SCC)-related adverse health outcomes. Although SK has the potential to progress to SCC, the risk of progression is low with no way of determining the risk factor for individual lesions.9 As most lesions do not progress and up to 26% of lesions regress spontaneously,10 the decision to treat depends on clinical judgement. Where treatment is provided, most SK lesions are cleared with cryotherapy, 5-fluorouracil (5-FU) cream or surgery.4 For people with multiple SK lesions, field-directed therapies (e.g. topical) are recommended to allow treatment of clinical and subclinical lesions (i.e. those not yet visible) within the treatment area.11
Imiquimod is an alternative when other treatments are not indicated
Consider topical treatments when other options are inappropriate or not preferred. In considering the sachet presentation of imiquimod in 2006, the Pharmaceutical Benefits Advisory Committee (PBAC) noted that there are no direct contraindications to surgical excision, cryotherapy and curettage,12therefore the choice of treatment will depend on clinical judgement. For any BCC for which non-surgical treatments are considered, treatment should be compared with surgery when discussing with patients the likelihood of complete clearance and the risk of recurrence.4
Risk of haematoma, infection and wound dehiscence and unacceptable cosmetic outcomes such as deformity, variation in pigmentation, hypertrophic or keloid scarring (especially for lesions of the upper chest and arms) are some of the disadvantages of surgical interventions that may favour other methods.4Other patient-related factors such as general fitness, coexisting serious medical conditions or the use of antiplatelet or anticoagulant medication also influence the choice of treatment.3 Patient choice, local availability of specialised services and the experience of the treating clinician are other factors to be considered.3,4
Use imiquimod on histologically favourable BCC lesions
Imiquimod is an alternative treatment for small primary sBCC.3,4,7,13–15 The safety and efficacy of imiquimod treatment for BCC of nodular or morpheaform histological subtypes have not been established.2 Confirm the diagnosis by skin biopsy before starting treatment with imiquimod.2
Use imiquimod on clinically favourable sBCC lesions that are low risk
Topical treatments are options for treating low-risk lesions,3 while surgery or radiotherapy should remain the standard for high-risk BCC lesions.3,7 Identify low risk of recurrence for individual lesions based on prognostic factors such as:
- smaller size (< 2 cm)3,4,13
- well-defined clinical margins3,4,13
- not fixed to nerve or vascular tissue3,4,13
- not located in sites such as the central face (especially around the eyes, nose, lips and ears)3,4,13 or lower legs.4,13
Control rates diminish with increasing size and depth of lesions such that 5-year overall estimated control rates of 95% are seen for lesions ≤ 2 cm2 but only 88% for lesions 2–5 cm2 in size.4 Large tumours (> 10–20 cm2) are usually deeply invasive beyond the subcutaneous tissue and are difficult to treat.4There are limited data for large sBCC treated with imiquimod. One small open-label trial showed lower clearance rates of 65% (95% confidence interval [CI] 38% to 86%) for larger tumours > 7.25 cm2 compared with 90% (95% CI 78% to 97%) for smaller tumours ranging from 2.0 to 7.25 cm2. 2,16
Multiple lesions may be problematic and should be considered for specialist referral.4 In the only trial involving multiple sBCCs treated by imiquimod, although the overall tumour response was comparable to those in studies of individual lesions, clearance of one tumour was not predictive of a response in all tumours, and some sites (e.g. lower limb) were associated with a lower clearance rate.17 Ensure continuous monitoring of all lesions during follow-up of patients with multiple lesions.
Imiquimod has not been evaluated for the treatment of sBCC lesions located within 1 cm of the hairline, eyes, nose, mouth or ears.2 Higher recurrence rates for BCC have been observed for all treatment modalities in the facial region — especially in proximity to the nose, eyes and ears — compared with non-facial sites.4 In the US and UK, imiquimod is not approved for lesions located on the face.15
Only use imiquimod on SK within a 25 cm2 field
Do not use imiquimod to treat an area of SK in excess of 25 cm2 due to the potential to cause local skin reactions (LSRs).2
Use imiquimod on suitable SK lesions on the face and scalp
Imiquimod has not been evaluated for treatment on the eyelids, the inside of the nostrils, ears, or the lip area inside the vermillion border and there are insufficient data to support the use of imiquimod on the hands and forearms. Imiquimod is not recommended for the treatment of SK lesions when there is marked hyperkeratosis or hypertrophy.2
Not PBS listed for genital warts
Although not having a PBS-subsidised indication for treatment of external genital and peri-anal warts (condyloma acuminata) in adults, imiquimod is TGA approved for this use. Imiquimod is a common self-applied treatment for external genital warts and may be used as adjunctive treatment to cryotherapy.18
Assess treatment success during and after treatment
Assess the clinical outcome of imiquimod therapy after treatment following regeneration of the treated area. For sBCC, assess the treated skin at least 6–12 weeks after completion of treatment.2 Longer follow-up periods for some people may be necessary, as persistent residual local effects such as persistent redness can complicate clinical evaluation.19,20
More than 40% of people will develop a second BCC within 3 years, representing a 10-fold increase in risk compared with the general population. Perform biopsy if there is any doubt about residual tumour. If histological evidence of clearance is not available, follow up initially at 3 months and then 6–12-monthly for up to 3 years. Include a full skin check for new lesions as well as inspection of the site of the original lesion at each examination.4
For SK, assess clearance after a 4-week treatment-free period and if any lesions persist repeat treatment for another 4 weeks.2
Imiquimod is not indicated for use on previously treated sBCC and there is no clinical experience in locally recurrent lesions or incompletely cleared lesions.2One study reported definitive outcomes through surgical intervention and suggested practitioners discuss failure rates with patients and recommend surgery for those with persistent lesions.21 The first opportunity for treatment is the best opportunity to achieve cure.4