Abstract
Background
Basal cell carcinoma (BCC) is the most common skin cancer. Surgical excision remains the standard of treatment, but several alternative treatment modalities exist.
Objectives
This review aims to provide a current analysis of evidence for the treatment of BCC; specifically, which treatments have the lowest recurrence rates and the best cosmetic outcomes.
Methods
We searched PubMed (January 1946 to August 2013), Ovid MEDLINE (2003–August 2013), the Cochrane Central Register of Controlled Trials (January 1993 to August 2013), and the Cochrane Database of Systematic Reviews (The Cochrane Library Issue 9, 2013) databases for randomized controlled trials, systematic reviews, or comparative studies for the treatment of BCC.
Results
We found 615 potential articles. Two independent reviewers selected 40 studies: 29 randomized controlled trials (RCTs), seven systematic reviews, and four nonrandomized prospective trials. Treatment modalities reviewed include surgical therapy, radiotherapy and cryotherapy, photodynamic therapy (PDT), topical imiquimod, topical 5-fluorouracil (5-FU), topical solasodine glycoalkaloids, topical ingenol mebutate, intralesional 5-FU, intralesional interferon (IFN), and oral hedgehog pathway inhibitors.
Conclusions
The available data suggest that surgical methods remain the gold standard in BCC treatment, with Mohs micrographic surgery typically utilized for high-risk lesions. Suitable alternate treatment options for appropriately selected primary low-risk lesions may include PDT, cryotherapy, topical imiquimod, and 5-FU. Radiotherapy is a suitable alternate for surgical methods for treatment in older patient populations. Electrodesiccation and curettage (ED&C) is a commonly used primary treatment option for low-risk lesions; however, there were no RCTs examining ED&C that met our inclusion criteria. New hedgehog pathway inhibitors are promising for the management of advanced BCC; however, side effects are a concern for some patients, and much remains to be learned regarding optimal treatment length, risk of recurrence, and potential development of resistance. There is insufficient evidence at present to make recommendations on topical solasodine glycoalkaloids, topical ingenol mebutate, and intralesional 5-FU and IFN-α. Overall continued research on the efficacy of treatment modalities is needed. In particular, studies should include histologic ascertainment of clearance, long-term follow-up, stratification based on tumor subtype, and comparison with surgical outcomes.
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References
Bader RS, Santacroce L, Diomede L, Kennedy AS. Basal cell carcinoma. Available online: http://emedicine.medscape.com/article/276624. Accessed Sept 2013.
Basal Cell and Squamous Cell Skin Cancers. 2013. http://www.nccn.org/professionals/physicians_gls/pdf/nmsc.pdf. Accessed Oct 2013.
Jerant AF, Johnson JT, Sheridan CD, Caffrey TJ. Early detection and treatment of skin cancer. Am Fam Physician. Jul 2000;62(2):357–8, 375–6, 381–2.
Roozeboom MH, Arits AH, Nelemans PJ, Kelleners-Smeets NW. Overall treatment success after treatment of primary superficial basal cell carcinoma: a systematic review and meta-analysis of randomized and nonrandomized trials. Br J Dermatol. 2012;167(4):733–56.
Miller SJ, Alam M, Andersen J, et al. Basal cell and squamous cell skin cancers. J Natl Compr Cancer Netw. 2010;8(8):836–64.
Kuijpers DI, Thissen MR, Neumann MH. Basal cell carcinoma: treatment options and prognosis, a scientific approach to a common malignancy. Am J Clin Dermatol. 2002;3(4):247–59.
Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.
Qaseem A, Snow V, Owens DK, Shekelle P, Clinical Guidelines Committee of the American College of Physicians. The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods. Ann Intern Med. 2010;153(3):194–9.
Mosterd K, Krekels GA, Nieman FH, et al. Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years’ follow-up. Lancet Oncol. 2008;9(12):1149–56.
Muller FM, Dawe RS, Moseley H, Fleming CJ. Randomized comparison of Mohs micrographic surgery and surgical excision for small nodular basal cell carcinoma: tissue-sparing outcome. Dermatol Surg. 2009;35(9):1349–54.
Kuijpers DI, Thissen MR, Berretty PJ, Ideler FH, Nelemans PJ, Neumann MH. Surgical excision versus curettage plus cryosurgery in the treatment of basal cell carcinoma. Dermatol Surg. 2007;33(5):579–87.
Rhodes LE, de Rie MA, Leifsdottir R, et al. Five-year follow-up of a randomized, prospective trial of topical methyl aminolevulinate photodynamic therapy vs surgery for nodular basal cell carcinoma. Arch Dermatol. 2007;143(9):1131–6.
Mosterd K, Thissen MR, Nelemans P, et al. Fractionated 5-aminolaevulinic acid-photodynamic therapy vs. surgical excision in the treatment of nodular basal cell carcinoma: results of a randomized controlled trial. Br J Dermatol. 2008;159(4):864–70.
Szeimies RM, Ibbotson S, Murrell DF, et al. A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8–20 mm), with a 12-month follow-up. J Eur Acad Dermatol Venereol. 2008;22(11):1302–11.
Avril MF, Auperin A, Margulis A, et al. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer. 1997;76(1):100–6.
van der Geer S, Martens J, van Roij J, et al. Imiquimod 5 % cream as pretreatment of Mohs micrographic surgery for nodular basal cell carcinoma in the face: a prospective randomized controlled study. Br J Dermatol. 2012;167(1):110–5.
Gaitanis G, Alexopoulos EC, Bassukas ID. Cryosurgery is more effective in the treatment of primary, non-superficial basal cell carcinomas when applied during and not prior to a five week imiquimod course: a randomized, prospective, open-label study. Eur J Dermatol. 2011;21(6):952–8.
Hall VL, Leppard BJ, McGill J, Kesseler ME, White JE, Goodwin P. Treatment of basal-cell carcinoma: comparison of radiotherapy and cryotherapy. Clin Radiol. 1986;37(1):33–4.
Wang I, Bendsoe N, Klinteberg CA, et al. Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial. Br J Dermatol. 2001;144(4):832–40.
Basset-Seguin N, Ibbotson SH, Emtestam L, et al. Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial. Eur J Dermatol. 2008;18(5):547–53.
Smucler R, Vlk M. Combination of Er:YAG laser and photodynamic therapy in the treatment of nodular basal cell carcinoma. Lasers Surg Med. 2008;40(2):153–8.
de Vijlder HC, Sterenborg HJ, Neumann HA, Robinson DJ, de Haas ER. Light fractionation significantly improves the response of superficial basal cell carcinoma to aminolaevulinic acid photodynamic therapy: five-year follow-up of a randomized, prospective trial. Acta Derm Venereol. 2012;92(6):641–7.
de Haas ER, Kruijt B, Sterenborg HJ, Martino Neumann HA, Robinson DJ. Fractionated illumination significantly improves the response of superficial basal cell carcinoma to aminolevulinic acid photodynamic therapy. J Invest Dermatol. 2006;126(12):2679–86.
Arits AH, Mosterd K, Essers BA, et al. Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial. Lancet Oncol. 2013;14(7):647–54.
Geisse J, Caro I, Lindholm J, Golitz L, Stampone P, Owens M. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol. 2004;50(5):722–33.
Schulze HJ, Cribier B, Requena L, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe. Br J Dermatol. 2005;152(5):939–47.
Ezughah FI, Dawe RS, Ibbotson SH, Fleming CJ. A randomized parallel study to assess the safety and efficacy of two different dosing regimens of 5 % imiquimod in the treatment of superficial basal cell carcinoma. J Dermatol Treat. 2008;19(2):111–7.
Garcia-Martin E, Gil-Arribas LM, Idoipe M, et al. Comparison of imiquimod 5 % cream versus radiotherapy as treatment for eyelid basal cell carcinoma. Br J Ophthalmol. 2011;95(10):1393–6.
Quirk C, Gebauer K, De’Ambrosis B, Slade HB, Meng TC. Sustained clearance of superficial basal cell carcinomas treated with imiquimod cream 5 %: results of a prospective 5-year study. Cutis. 2010;85(6):318–24.
Gollnick H, Barona CG, Frank RG, et al. Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term follow-up study in Europe. Eur J Dermatol. 2008;18(6):677–82.
Quirk C, Gebauer K, Owens M, Stampone P. Two-year interim results from a 5-year study evaluating clinical recurrence of superficial basal cell carcinoma after treatment with imiquimod 5% cream daily for 6 weeks. Australas J Dermatol. 2006;47(4):258–65.
Gollnick H, Barona CG, Frank RG, et al. Recurrence rate of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream: interim 2-year results from an ongoing 5-year follow-up study in Europe. Eur J Dermatol. 2005;15(5):374–81.
Romagosa R, Saap L, Givens M, et al. A pilot study to evaluate the treatment of basal cell carcinoma with 5-fluorouracil using phosphatidyl choline as a transepidermal carrier. Dermatol Surg. 2000;26(4):338–40.
Punjabi S, Cook LJ, Kersey P, Marks R, Cerio R. Solasodine glycoalkaloids: a novel topical therapy for basal cell carcinoma. A double-blind, randomized, placebo-controlled, parallel group, multicenter study. Int J Dermatol. 2008;47(1):78–82.
Siller G, Rosen R, Freeman M, Welburn P, Katsamas J, Ogbourne SM. PEP005 (ingenol mebutate) gel for the topical treatment of superficial basal cell carcinoma: results of a randomized phase IIa trial. Australas J Dermatol. 2010;51(2):99–105.
Cornell RC, Greenway HT, Tucker SB, et al. Intralesional interferon therapy for basal cell carcinoma. J Am Acad Dermatol. 1990;23(4 Pt 1):694–700.
Edwards L, Tucker SB, Perednia D, et al. The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas. Arch Dermatol. 1990;126(8):1029–32.
Miller BH, Shavin JS, Cognetta A, et al. Nonsurgical treatment of basal cell carcinomas with intralesional 5-fluorouracil/epinephrine injectable gel. J Am Acad Dermatol. 1997;36(1):72–7.
Orenberg EK, Miller BH, Greenway HT, et al. The effect of intralesional 5-fluorouracil therapeutic implant (MPI 5003) for treatment of basal cell carcinoma. J Am Acad Dermatol. 1992;27(5 Pt 1):723–8.
Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012;366(23):2180–8.
Patel RV, Frankel A, Goldenberg G. An update on nonmelanoma skin cancer. J Clin Aesthet Dermatol. 2011;4(2):20–7.
Ad Hoc Task F, Connolly SM, Baker DR, et al. AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery. J Am Acad Dermatol. 2012;67(4):531–50.
Love WE, Bernhard JD, Bordeaux JS. Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review. Arch Dermatol. 2009;145(12):1431–8.
Bath-Hextall FJ, Perkins W, Bong J, Williams HC. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev. 2007;(1):CD003412.
Ormerod A, Rajpara S, Craig F. Basal cell carcinoma. Clin Evid (Online). 2010 Apr 6.
Foley P, Freeman M, Menter A, et al. Photodynamic therapy with methyl aminolevulinate for primary nodular basal cell carcinoma: results of two randomized studies. Int J Dermatol. 2009;48(11):1236–45.
Thissen MR, Neumann MH, Schouten LJ. A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol. 1999;135(10):1177–83.
Mosterd K, Arits AH, Thissen MR, Kelleners-Smeets NW. Histology-based treatment of basal cell carcinoma. Acta Derm Venereol. 2009;89(5):454–8.
Kwasniak LA, Garcia-Zuazaga J. Basal cell carcinoma: evidence-based medicine and review of treatment modalities. Int J Dermatol. 2011;50(6):645–58.
Disclosures
J.M. Mackay-Wiggan served as an investigator for Genentech, and her department receives compensation for pharmaceutical-sponsored research that does not benefit her directly.
C.M. Clark and M. Furniss have no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to prepare this review.
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Clark, C.M., Furniss, M. & Mackay-Wiggan, J.M. Basal Cell Carcinoma: An Evidence-Based Treatment Update. Am J Clin Dermatol 15, 197–216 (2014). https://doi.org/10.1007/s40257-014-0070-z
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DOI: https://doi.org/10.1007/s40257-014-0070-z