A BRIEF REVIEW OF TREATMENT MODALITIES FOR NON-MELANOMA SKIN CANCER
Keywords:Non-melanoma skin cancer, Mohs micrographic surgery, Photodynamic therapy, Chemotherapy, Immunotherapy
NMSC (Non-melanoma skin cancer) is the most commonly occurring malignancy in Caucasians. Out of all diagnosed NMSC cases, 95% of the cases are of basal cell carcinoma and squamous cell carcinoma. The therapeutic approaches to cure or ultimately rescue the skin area affected by NMSC include surgical methods, photodynamic therapy, radiation therapy, immunotherapy, and chemotherapy. This article aims to provide a brief overview of the preliminary mechanism of action, clinical studies, advantages, and disadvantages of currently available treatment modalities.
Linares MA, Zakaria A, Nizran P. Skin cancer. Prim Care 2015;42:645-59.
Albert A, Knoll MA, Conti JA, Zbar RI. Non-melanoma skin cancers in the older patient. Curr Oncol Rep 2019;21:79.
Zink A. Trends in the treatment and prevention of keratinocyte carcinoma (non-melanoma skin cancer). Curr Opin Pharmacol 2019;46:19-23.
Lomas A, Leonardi-Bee J, Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol 2012;166:1069-80.
Leiter U, Eigentler T, Garbe C. Epidemiology of skin cancer. Adv Exp Med Biol 2014;810:120-40.
Fahradyan A, Howell AC, Wolfswinkel EM, Tsuha M, Sheth P, Wong AK. Updates on the management of non-melanoma skin cancer (NMSC). Healthcare (Basel, Switzerland) 2017;5:82.
Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the U.S. population, 2012. JAMA Dermatol 2015;151:1081-6.
Wollina U, Koch A, Schonlebe J, Tchernev G. Carcinosarcoma of skin a rae non-melanoma skin cancer (case review). Georgian Med News 2017;263:7-10.
Losquadro WD. Anatomy of the skin and the pathogenesis of nonmelanoma skin cancer. Facial Plast Surg Clin North Am 2017;25:283-9.
Kauvar AN, Cronin TJ, Roenigk R, Hruza G, Bennett R. Consensus for nonmelanoma skin cancer treatment: Basal cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg 2015;41:550-71.
Jennings L, Schmults CD. Management of high-risk cutaneous squamous cell carcinoma. J Clin Aesthet Dermatol 2010;3:39-48.
Lv R, Sun Q. A network meta-analysis of non-melanoma skin cancer (NMSC) treatments: Efficacy and safety assessment. J Cell Biochem 2017;118:3686-95.
Hamdan IM, Donnelly RF. Microneedle-assisted photodynamic therapy: Delivery of a NIR photosensitiser for the treatment of skin cancers. Photodiagn Photodyn Ther 2017;17:A63.
Griffin LL, Lear JT. Photodynamic therapy and non-melanoma skin cancer. Cancers (Basel) 2016;8:98.
Cohen DK, Lee PK. Photodynamic therapy for non-melanoma skin cancers. Cancers (Basel) 2016;8:90.
Cheraghi N, Cognetta A, Goldberg D. Radiation therapy in dermatology: Non-melanoma skin cancer. J Drugs Dermatol 2017;16:464-9.
Dlugosz A, Agrawal S, Kirkpatrick P. Vismodegib. Nat Rev Drug Discov 2012;11:437-8.
Wong E, Axibal E, Brown M. Mohs micrographic surgery. Facial Plast Surg Clin North Am 2019;27:15-34.
Mohs FE. Chemosurgery in cancer, gangrene and infections. AMA Arch Derm 1957;76:155-6.
Stegman SJ, Tromovitch TA. Fresh tissue chemosurgery for tumors of the nose. Eye Ear Nose Throat Mon 1976;55:26-30.
Mohs FE. Chemosurgery for skin cancer: Fixed tissue and fresh tissue techniques. Arch Dermatol 1976;112:211-5.
Brodland DG, Amonette R, Hanke CW, Robins P. The history and evolution of Mohs micrographic surgery. Dermatol Surg 2000;26:303-7.
Nemeth SA, Lawrence N. Site identification challenges in dermatologic surgery: A physician survey. J Am Acad Dermatol 2012;67:262-8.
Kouba DJ, LoPiccolo MC, Alam M, Bordeaux JS, Cohen B, Hanke CW, et al. Guidelines for the use of local anesthesia in office-based dermatologic surgery. J Am Acad Dermatol 2016;74:1201-19.
Greenway T, Greenway T. Mohs micrographic surgery for skin cancer. Aust Dermatol 1991;32:159-64.
Rowe DE, Carroll RJ, Day CL. Long-term recurrence rates in previously untreated (primary) basal cell carcinoma: Implications for patient follow-up. J Dermatol Surg Oncol 1989;15:315-28.
Rowe DE, Carroll RJ, Day CL. Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 1989;15:424-31.
Guy GP, Machlin SR, Ekwueme DU, Yabroff KR. Prevalence and costs of skin cancer treatment in the U.S., 2002-2006 and 2007-2011. Am J Prev Med 2015;48:183-7.
Lawrence CM. Mohs’ micrographic surgery for basal cell carcinoma. Clin Exp Dermatol 1999;24:130-3.
Bernstein PE. Mohs ’98: Single-procedure mohs surgery with immediate reconstruction. Otolaryngol Neck Surg 1999;120:184-9.
Shriner DL, McCoy DK, Goldberg DJ, Wagner RF. Mohs micrographic surgery. J Am Acad Dermatol 1998;39:79-97.
Abide JM, Nahai F, Bennett RG. The meaning of surgical margins. Plast Reconstr Surg 1984;73:492-7.
Tolkachjov SN, Brodland DG, Coldiron BM, Fazio MJ, Hruza GJ, Roenigk RK, et al. Understanding mohs micrographic surgery: A review and practical guide for the nondermatologist. Mayo Clin Proc 2017;92:1261-71.
Marzuka AG, Book SE. Basal cell carcinoma: Pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management. Yale J Biol Med 2015;88:167-79.
Rowe DE, Carroll RJ, Day CL. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol 1992;26:976-90.
Telfer NR, Colver GB, Morton CA. Guidelines for the management of basal cell carcinoma. Br J Dermatol 2008;159:35-48.
Clark WL. Oscillatory desiccation in the treatment of accessible malignant growths and minor surgical conditions. J Adv Ther 1910;29:169-83.
Goldman GT. The current status of curettage and electrodesiccation. Dermatol Clin 2002;20:569-78.
Wigglesworth E. The curette in dermal therapeutics. Bost Med Surg J 1876;94:143-6.
Williamson GS, Jackson R. Treatment of squamous cell carcinoma of the skin by electrodesiccation and curettage. Can Med Assoc J 1964;90:408-13.
McDaniel WE. Therapy for basal cell epitheliomas by curettage only. Further study. Arch Dermatol 1983;119:901-3.
Reymann F. 15 years’ experience with treatment of basal cell carcinomas of the skin with curettage. Acta Derm Venereol Suppl (Stockh) 1985;120:56-9.
Kauvar AN, Arpey CJ, Hruza G, Olbricht SM, Bennett R, Mahmoud BH. Consensus for nonmelanoma skin cancer treatment, Part II: Squamous cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg 2015;41:1214-40.
Blixt E, Nelsen D, Stratman E. Recurrence rates of aggressive histologic types of basal cell carcinoma after treatment with electrodesiccation and curettage alone. Dermatol Surg 2013;39:719-25.
Barlow JO, Zalla MJ, Kyle A, DiCaudo DJ, Lim KK, Yiannias JA. Treatment of basal cell carcinoma with curettage alone. J Am Acad Dermatol 2006;54:1039-45.
Rodriguez-Vigil T, Vazquez-Lapez F, Perez-Oliva N. Recurrence rates of primary basal cell carcinoma in facial risk areas treated with curettage and electrodesiccation. J Am Acad Dermatol 2007;56:91-5.
Spiller WF, Spiller RF. Treatment of basal cell epithelioma by curettage and electrodesiccation. J Am Acad Dermatol 1984;11:808-14.
Kaur S, Thami GP, Kanwar AJ. Basal cell carcinoma--treatment with cryosurgery. Indian J Dermatol Venereol Leprol 2003;69:188-90.
Lewin JM, Carucci JA. Advances in the management of basal cell carcinoma. F1000Prime Rep 2015;8:53.
Thissen MR, Neumann MH, Schouten LJ. A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol 1999;135:1177-83.
Lucena SR, Salazar N, Gracia-Cazana T, Zamarron A, Gonzalez S, Juarranz A, et al. Combined treatments with photodynamic therapy for non-melanoma skin cancer. Int J Mol Sci 2015;16:25912-33.
Choudhary S, Nouri K, Elsaie ML. Photodynamic therapy in dermatology: A review. Lasers Med Sci 2009;24:971-80.
Mfouo-Tynga I, Abrahamse H. Cell death pathways and phthalocyanine as an efficient agent for photodynamic cancer therapy. Int J Mol Sci 2015;16:10228-41.
Henderson BW, Dougherty TJ. How does photodynamic therapy work? Photochem Photobiol 1992;55:145-57.
Christensen E, Warloe T, Kroon S, Funk J, Helsing P, Soler AM, et al. Mork, guidelines for practical use of MAL-PDT in non-melanoma skin cancer. J Eur Acad Dermatol Venereol 2010;24:505-12.
Suarez-Valladares MJ, Rodriguez-Prieto MA, Serra-Llusa R. Penetration of 630nm laser and 5-aminolevulinic acid in tissue with intralesional photodynamic therapy. Photodiagn Photodyn Ther 2016;16:166-8.
Sotiriou E, Apalla Z, Vrani F, Lazaridou E, Vakirlis E, Lallas A, et al. Daylight photodynamic therapy vs. Conventional photodynamic therapy as skin cancer preventive treatment in patients with face and scalp cancerization: An intra-individual comparison study. J Eur Acad Dermatol Venereol 2017;31:1303-7.
Soleymani T, Abrouk M, Kelly KM. An analysis of laser therapy for the treatment of nonmelanoma skin cancer. Dermatol Surg 2017;43:615-24.
Jerjes W, Upile T, Betz CS, El Maaytah M, Abbas S, Wright A, Hopper C. The application of photodynamic therapy in the head and neck. Dent Update 2007;34:478-86.
Apalla Z, Sotiriou E, Chovarda E, Lefaki I, Devliotou-Panagiotidou D, Ioannides D. Skin cancer: Preventive photodynamic therapy in patients with face and scalp cancerization. A randomized placebo-controlled study. Br J Dermatol 2010;162:171-5.
Anderson RR, Parrish JA. Selective photothermolysis: Precise microsurgery by selective absorption of pulsed radiation. Science 1983;220:524-7.
Anderson RR. Lasers for dermatology and skin biology. J Invest Dermatol 2013;133:E21-3.
Christensen E, Skogvoll E, Viset T, Warloe T, Sundstrom S. Photodynamic therapy with 5-aminolaevulinic acid, dimethylsulfoxide and curettage in basal cell carcinoma: A 6-year clinical and histological follow-up. J Eur Acad Dermatol Venereol 2009;23:58-66.
Wang I, Bendsoe N, Klinteberg CA, Enejder AM, Andersson-Engels S, Svanberg S, et al. Photodynamic therapy vs. cryosurgery of basal cell carcinomas: Results of a phase III clinical trial. Br J Dermatol 2001;144:832-40.
Matei C, Tampa M, Poteca T, Panea-Paunica G, Georgescu SR, Ion RM, et al. photodynamic therapy in the treatment of basal cell carcinoma. 2013;6:50-4.
Itkin A, Gilchrest BA. Delta-Aminolevulinic acid and blue light photodynamic therapy for treatment of multiple basal cell carcinomas in two patients with nevoid basal cell carcinoma syndrome. Dermatol Surg 2004;30:1054-61.
Soler AM, Warloe T, Berner A, Giercksky K. A follow-up study of recurrence and cosmesis in completely responding superficial and nodular basal cell carcinomas treated with methyl 5-aminolaevulinate-based photodynamic therapy alone and with prior curettage. Br J Dermatol 2001;145:467-71.
Horn M, Wolf P, Wulf HC, Warloe T, Fritsch C, Rhodes LE, Kaufmann R, et al. Topical methyl aminolaevulinate photodynamic therapy in patients with basal cell carcinoma prone to complications and poor cosmetic outcome with conventional treatment. Br J Dermatol 2003;149:1242-9.
Pauwels C, Mazereeuw-Hautier J, Basset-Seguin N, Livideanu C, Viraben R, Paul C, et al. Topical methyl aminolevulinate photodynamic therapy for management of basal cell carcinomas in patients with basal cell nevus syndrome improves patient’s satisfaction and reduces the need for surgical procedures. J Eur Acad Dermatol Venereol 2011;25:861-4.
David CV. Electronic brachytherapy and superficial radiation therapy: Will you be adding it to your practice? Cutis 2013;92:E16-8.
McGregor S, Minni J, Herold D. Superficial radiation therapy for the treatment of nonmelanoma skin cancers. J Clin Aesthet Dermatol 2015;8:12-14.
Bath-Hextall FJ, Perkins W, Bong J, Williams HC. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev 2007;1:CD003412.
Schulte KW, Lippold A, Auras C, Bramkamp G, Breitkopf C, Elsmann HJ, et al. Soft x-ray therapy for cutaneous basal cell and squamous cell carcinomas. J Am Acad Dermatol 2005;53:993-1001.
Skowronek J. Brachytherapy in the treatment of skin cancer: An overview. Postep Dermatol Alergol 2015;32:362-7.
Morrison WH, Garden AS, Ang KK. Radiation therapy for nonmelanoma skin carcinomas. Clin Plast Surg 1997;24:719-29.
Mendenhall WM, Amdur RJ, Hinerman RW, Werning JW, Villaret DB, Mendenhall NP. Head and neck mucosal melanoma. Am J Clin Oncol 2005;28:626-30.
Han A, Ratner D. What is the role of adjuvant radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion? Cancer 2007;109:1053-9.
Garcia-Serra A, Hinerman RW, Mendenhall WM, Amdur RJ, Morris CG, Williams LS, et al. Carcinoma of the skin with perineural invasion. Head Neck 2003;25:1027-33.
Micali G, Lacarrubba F, Bhatt K, Nasca MR. Medical approaches to non-melanoma skin cancer. Expert Rev Anticancer Ther 2013;13:1409-21.
Krähn G, Leiter U, Kaskel P, Udart M, Utikal J, Bezold G, et al. Coexpression patterns of EGFR, HER2, HER3 and HER4 in non-melanoma skin cancer. Eur J Cancer 2001;37:251-9.
Amaral T, Garbe C. Non-melanoma skin cancer: New and future synthetic drug treatments. Expert Opin Pharmacother 2017;18:689-99.
Falchook GS, Leidner R, Stankevich E, Piening B, Bifulco C, Lowy I, et al. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer 2016;4:70.
Askew DA, Mickan SM, Soyer HP, Wilkinson D. Effectiveness of 5-fluorouracil treatment for actinic keratosis--a systematic review of randomized controlled trials. Int J Dermatol 2009;48:453-63.
Klein E, Milgrom H, Helm F, Ambrus J, Traenkel HL, Stoll HS. Tumors of the skin: Effects of local use of cytostatic agents. Skin (Los Angeles) 1962;1:81-7.
Micali G, Lacarrubba F, Dinotta F, Massimino D, Nasca MR. Treating skin cancer with topical cream. Expert Opin Pharmacother 2010;11:1515-27.
McGillis ST, Fein H. Topical treatment strategies for non-melanoma skin cancer and precursor lesions. Semin Cutan Med Surg 2004;23:174-83.
Weinberg JM. Topical therapy for actinic keratoses: Current and evolving therapies. Rev Recent Clin Trials 2006;1:53-60.
Gross K, Kircik L, Kricorian G. 5% 5-Fluorouracil cream for the treatment of small superficial Basal cell carcinoma: Efficacy, tolerability, cosmetic outcome, and patient satisfaction. Dermatol Surg 2007;33:433-9; discussion 440.
Romagosa R, Saap L, Givens M, Salvarrey A, He JL, Hsia SL, 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;26:338-340.
Klein E, Stoll HL, Milgrom H, Case RW, Traenkle HL, Graham S, et al. tumors of the skin. IV. double-blind study on effects of local administration of anti-tumor agents in basal cell carcinoma. J Invest Dermatol 1965;44:351-3.
Shelley WB, Wood MG. Nodular superficial pigmented basal cell epitheliomas. Arch Dermatol 1982;118:928-30.
Ceovic R, Smolkovic N, Pasic A, Kostovic K, Hrsan D. Multiple basal cell carcinomas of lower legs with stasis dermatitis: A therapeutic challenge. Acta Dermatovenerol Croat 2012;20:191-6.
Bargman HB, Hochman J. Topical treatment of Bowen’s disease with 5-fluorouracil. J Cutan Med Surg 2003;7:101-5.
Stockfleth E, Kerl H, Zwingers T, Willers C. Low-dose 5-fluorouracil in combination with salicylic acid as a new lesion-directed option to treat topically actinic keratoses: Histological and clinical study results. Br J Dermatol 2011;165:1101-8.
Johnson MR, Hageboutros A, Wang K, High L, Smith JB, Diasio RB. Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. Clin Cancer Res 1999;5:2006-11.
Lacarrubba F, Nasca MR, Micali G. Advances in the use of topical imiquimod to treat dermatologic disorders. Ther Clin Risk Manag 2008;4:87-97.
Patel GK, Goodwin R, Chawla M, Laidler P, Price PE, Finlay AY, et al. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen’s disease): A randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol 2006;54:1025-32.
Schon M, Schon MP. The antitumoral mode of action of imiquimod and other imidazoquinolines. Curr Med Chem 2007;14:681-7.
Li VW, Li WW, Talcott KE, Zhai AW. Imiquimod as an antiangiogenic agent. J Drugs Dermatol 2005;4:708-17.
Hadley G, Derry S, Moore RA. Imiquimod for actinic keratosis: Systematic review and meta-analysis. J Invest Dermatol 2006;126:1251-5.
Geisse JK, Rich P, Pandya A, Gross K, Andres K, Ginkel A, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: A double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol 2002;47:390-8.
Arits AH, Mosterd K, Essers BA, Spoorenberg E, Sommer A, De Rooij MJ, et al. Kelleners-smeets, 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;14:647-54.
Rosen RH, Gupta AK, Tyring SK. Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: Rapid lesion necrosis followed by lesion-specific immune response. J Am Acad Dermatol 2012;66:486-93.
Fallen RS, Gooderham M. Ingenol mebutate: An introduction. Skin Ther Lett 2012;17:1-3.
Patel RV, Frankel A, Goldenberg G. An update on nonmelanoma skin cancer. J Clin Aesthet Dermatol 2011;4:20-7.
Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B. Ingenol mebutate gel for actinic keratosis. N Engl J Med 2012;366:1010-9.
Amini S, Viera MH, Valins W, Berman B. Nonsurgical innovations in the treatment of nonmelanoma skin cancer. J Clin Aesthet Dermatol 2010;3:20-34.
Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Retinoids in the treatment of skin aging: An overview of clinical efficacy and safety. Clin Interv Aging 2006;1:327-48.
Cuevas P, Angulo J, Bourdier AC, Salgüero I. Treatment of infiltrative basal cell carcinomas by inhibiting the fibroblast growth factor (FGF)- signal transducer and activator of transcription (STAT)-3 signalling pathways. J Cancer Sci Ther 2012;1:S3.
Peris K, Fargnoli MC, Chimenti S. Preliminary observations on the use of topical tazarotene to treat basal-cell carcinoma. N Engl J Med 1999;341:1767-8.
Kim DJ, Kim J, Spaunhurst K, Montoya J, Khodosh R, Chandra K, et al. Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma. J Clin Oncol 2014;32:745-51.
Odom D, Mladsi D, Purser M, Kaye JA, Palaka E, Charter A, et al. A matching-adjusted indirect comparison of sonidegib and vismodegib in advanced basal cell carcinoma. J Skin Cancer 2017;2017:6121760.
Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012;366:2171-9.
Dubas LE, Ingraffea A. Nonmelanoma skin cancer. Facial Plast Surg Clin North Am 2013;21:43-53.
Maubec E, Petrow P, Scheer-Senyarich I, Duvillard P, Lacroix L, Gelly J, et al. Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol 2011;29:3419-26.
Preneau S, Rio E, Brocard A, Peuvrel L, Nguyen JM, Quereux G, et al. Efficacy of cetuximab in the treatment of squamous cell carcinoma.J Dermatolog Treat 2014;25:424-7.
O’Bryan K, Sherman W, Niedt GW, Taback B, Manolidis S, Wang A, et al. An evolving paradigm for the workup and management of high-risk cutaneous squamous cell carcinoma. J Am Acad Dermatol 2013;69:595-602.e1.
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