Surgery Versus Combined Treatment With Curettage and Imiquimod for Nodular Basal Cell Carcinoma

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 (SE), but not all patients are eligible for surgery. In patients with multiple BCCs and older patients, surgery may lead to significant morbidity, and in some cases, it may result in disfiguring scarring. For these reasons 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 and specialized nurses. 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. Our group investigated the efficacy of those three therapies and found that after 3 years, BCCs treated with IMQ had a significant lower risk of recurrence, compared to the other therapies. A recent study suggests that IMQ, besides being an immune-response modifier, also directly inhibits sonic hedgehog (SHH) signalling, the most important pathway active in BCCs. This targeted effect of IMQ very likely explains the superior therapeutic effect. Treatment of nodular BCC (nBCC) with IMQ has been investigated. Without prior curettage, high efficacy rates were found, although efficacy was still slightly inferior to SE. The investigators hypothesize that the effectiveness of IMQ following prior curettage will not be inferior to SE and that the benefits will be a higher patient satisfaction and lower healthcare costs. A recently published discreet choice experiment showed that patients preferred IMQ to surgery regardless of previous experience of BCC symptoms and treatment.

Sex

All

Minimum age

18 Years

Maximum age

90 Years

Inclusion Criteria:

* Adults aged 18 years or older
* Primary histologically proven nodular BCC ≥ 4mm and ≤ 20mm in diameter. (If the tumour exhibits additional sBCC characteristics, but also contains nodular component that extend into the reticular dermis, the tumour will be classified as nBCC with superficial components and will be included).
* Comorbidities may not interfere with study treatment
* Capable to understand instructions

Exclusion Criteria:

* A nodular BCC located in the H-zone of the face or hairy scalp
* Recurrent (previously treated) nBCC
* Aggressive BCC subtypes (morphoea, micronodular, or BCC with squamous differentiation)
* Life expectancy of less than five years
* Breast-feeding or pregnant women
* Serious comorbidities
* Use of immunosuppressive medication during the trial period or within 30 days before enrolment
* Patients with genetic skin cancer disorders

• BACKGROUNDBath-Hextall F, Ozolins M, Armstrong SJ, Colver GB, Perkins W, Miller PS, Williams HC; Surgery versus Imiquimod for Nodular Superficial basal cell carcinoma (SINS) study group. Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):96-105. doi: 10.1016/S1470-2045(13)70530-8. Epub 2013 Dec 11. PMID 24332516
• DERIVEDVerkouteren BJA, Nelemans PJ, Sinx KAE, Kelleners-Smeets NWJ, Winnepenninckx VJL, Arits AHMM, Mosterd K. Imiquimod Cream Preceded by Superficial Curettage vs Surgical Excision for Nodular Basal Cell Carcinoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Dermatol. 2025 Mar 1;161(3):299-304. doi: 10.1001/jamadermatol.2024.5572. PMID 39878970
• DERIVEDSinx KAE, Nelemans PJ, Kelleners-Smeets NWJ, Winnepenninckx VJL, Arits AHMM, Mosterd K. Surgery versus combined treatment with curettage and imiquimod for nodular basal cell carcinoma: One-year results of a noninferiority, randomized, controlled trial. J Am Acad Dermatol. 2020 Aug;83(2):469-476. doi: 10.1016/j.jaad.2020.04.053. Epub 2020 Apr 19. PMID 32320773