Surgical excision versus combined therapy with Curettage and Imiquimod for Nodular Basal Cell Carcinoma: an open, non-inferiority, randomized controlled trial

Basal cell carcinoma (BCC) is a slow-growing, locally invasive malignant
epidermal skin tumour. It is the most common malignant disease in Caucasians,
representing approximately 80% of all cases of skin cancer and is therefore an
important health problem. In the Netherlands incidence rates are 165 for men
and 157 for women per 100.000 person-years, and these rates are rising with
3-10% every year.
A simplified histological classification of BCCs includes the following three
subtypes: nodular, superficial and infiltrative variants, with the nodular
variant being the most frequent type. Although a characteristic feature of BCCs
is their low risk to metastasize, if untreated they may be locally invasive and
may induce considerable functional and cosmetic morbidity.

The gold standard treatment of all histological BCC subtypes is surgical
excision, but not all patients are eligible for surgery. Surgery may lead to
significant morbidity, and in some cases, it may result in disfiguring
scarring. For this reason and to reduce workload and costs in the healthcare
system, there is a growing demand for alternative, non-invasive, treatments. An
advantage of non-invasive treatment options is that they can be performed by
other healthcare professionals, such as general practitioners, specialized
nurses or professionals in elderly homes.

For treatment of superficial BCCs (sBCC) non-invasive treatments, such as
topical imiquimod (IMQ), 5-fluorouracil (5-FU) or photodynamic therapy (PDT)
are already commonly used. A recent study suggests that IMQ, besides being an
immune-response modifier, can also directly inhibit sonic hedgehog (SHH)
signalling, the most important pathway active in BCCs. This targeted effect of
IMQ very likely explains the superior therapeutic effect compared to other
non-invasive therapies. In literature, effective treatment of nodular BCC
(nBCC) with IMQ has been described, however, efficacy was inferior to surgical
excision. We hypothesize that the effectiveness of IMQ will rise by performing
prior curettage to IMQ therapy.

Primary objective: To compare long-term efficacy of curettage prior to IMQ 5%
cream (Aldara®) therapy versus standard surgical excision in primary nBCC.

Secondary objective: To assess compliance, pain, cosmetic outcomes, patient
satisfaction, patient preference and cost-effectiveness.

Open-label, parallel-group, non-inferiority, randomized controlled trial

Studyarm 1: IMQ 5% cream once daily, 5 days a week, for six weeks, with prior
curettage.
Studyarm 2: Standard surgical excision with 3-5 mm margins.

First visit, description of the lesion, biopsy , telephonic consultation,
surgical excision and two to three control visits are part of regular care of
nBCC. Treatment with IMQ 5% cream and one control (after 5 year follow-up)
visit are part of the study.
A potential risk when participating in this study is an allergic skin reaction
for one of the components of the IMQ 5% cream.
Local skin reactions at application site represent a special safety issue for
topically applied treatments. Local skin reactions can be easily controlled and
therefore are acceptable for the subjects. In case of residu, an surgical
excision has to be performed. We do not expect any other risks.