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Advanced basal cell carcinoma

Das fortgeschrittene Basalzellkarzinom

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Summary

Basal cell carcinoma (BCC) is the most common skin malignancy worldwide. Ultraviolet light exposure is the best known exogenous factor in BCC development. This is also the target for primary prevention. Advanced BCC include locally advanced tumors and metastatic tumors. Prognosis is worse compared to stage I and II BCCs. Mohs or micrographically controlled surgery is the gold standard of treatment. In patients with tumors that cannot be completely removed radiotherapy was the only alternative in the past. More recently new drugs for targeted therapy of signaling pathways like sonic hedgehog or epidermal growth factor receptor became available. More small molecules are under investigation. Since the complete response rates are limited, future research has to evaluate their combination with surgery.

Zusammenfassung

Das Basalzellkarzinom (BCC) ist weltweit der häufigste maligne Tumor. Die Exposition gegenüber ultravioletter Strahlung gilt als bekanntester exogener Faktor in der BCC-Entwicklung. Hierauf zielen auch alle primären Präventionsmaßnahmen. Unter dem Begriff der fortgeschrittenen BCC werden lokal ausgedehnte Tumore und metastasierende Tumore zusammengefaßt. Ihre Prognose ist deutlich schlechter als bei den Stadien I und II. Mohs- oder mikrographisch-kontrollierte Chirurgie gilt als Goldstandard in der Behandlung. Bei Patienten, wo eine komplette Exzision des Tumors unmöglich war, blieb in der Vergangenheit nur die Strahlentherapie als Alternative. In jüngerer Zeit gibt es Medikamente für eine zielgerichtete Behandlung mit Beeinflussung von Signalkaskaden wie Sonic hedgehog oder epidermalem Wachstumsfaktor-Rezeptor. Weitere kleine Moleküle werden geprüft. Da bislang die kompletten Remissionsraten unter dieser Therapie limitiert sind, gilt es ihre bestmögliche Kombination mit der Chirurgie zu bestimmen.

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References

  1. 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.

    Article  PubMed  CAS  Google Scholar 

  2. Fartasch M, Diepgen TL, Schmitt J, Drexsler H. The relationship between occupational sun exposure and nonmelanoma skin cancer. Dtsch Ärztebl Int. 2012;109:715–20.

    PubMed  Google Scholar 

  3. Wollina U. Nonmelanoma skin cancer on the rise. J Cutan Aesthet Surg. 2012;5:11.

    PubMed  Google Scholar 

  4. Chinem VP, Mior HA. Epidemiology of basal cell carcinoma. An Bras Dermatol. 2011;86:292–305.

    Article  PubMed  Google Scholar 

  5. Adinarayan M, Krishnamurthy SP. Clinicopathological evaluation of nonmelanoma skin cancer. Indian J Dermatol. 2011;56:670–2.

    Article  PubMed  Google Scholar 

  6. Chang JM, Gao XM. Clinical and histopathological characteristics of basal cell carcinoma in Chinese patients. Chin Med J (Engl). 2013;126:211–4.

    PubMed  Google Scholar 

  7. Moser S, Borm J, Michic-Probst D, Jacobsen C, Kruse-Gujer AL. Metastatic basal cell carcinoma: report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013. doi:pii:S2212-4403(12)00398-7.

  8. Greinert R, Boniol M. Skin cancer—primary and secondary prevention (information campaigns and screening)—with a focus on children & sunbeds. Progr Biophys Mol Biol. 2011;107:473–6.

    Article  Google Scholar 

  9. Wollina U. Addiction to tanning—a new cause of early onset of nonmelanoma skin cancer. Open Dermatol J. 2009;3:144–9.

    Article  Google Scholar 

  10. Göppner D, Leverkus M. Basal cell carcinoma: from the molecular understanding of the pathogenesis to targeted therapy of progressive disease. J Skin Cancer. 2011;2011:650258.

    PubMed  Google Scholar 

  11. Parren LJ, Frank J. Hereditary tumour syndromes featuring basal cell carcinomas. Br J Dermatol 2011;165:30–4.

    Article  PubMed  CAS  Google Scholar 

  12. de Vries E, Arnold M, Altsitsiadis E, Trakatelli M, Hinrichs B, Stockfleth E, et al. Potential impact of interventions resulting in reduced exposure to ultraviolet (UV) radiation (UVA and UVB) on skin cancer incidence in four European countries, 2010–2050. Br J Dermatol. 2012;167(Suppl 2):53–62.

    Article  PubMed  Google Scholar 

  13. Burnett ME, Wang SQ. Current sunscreen controversies: a critical review. Photodermatol Photoimmunol Photomed. 2011;27:58–67.

    Article  PubMed  CAS  Google Scholar 

  14. Weinstock MA, Bingham SF, Digiovanna JJ, Rizzo AE, Marcolivio K, Hall R, et al. Tretinoin and the prevention of keratinocyte carcinoma (basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial. J Invest Dermatol. 2012;132:1583–90.

    Article  PubMed  CAS  Google Scholar 

  15. Lien MH, Fenske NA, Glass LF. Advances in the chemoprevention of nonmelanoma skin cancer in high-risk organ transplant recipients. Semin Oncol. 2012;39:134–8.

    Article  PubMed  CAS  Google Scholar 

  16. Elmets CA, Viner JL, Pentland AP, Cantrell W, Lin HY, Bailey H, et al. Chemoprevention of nonmelanoma skin cancer with celecoxib: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2010;102:1835–44.

    Article  PubMed  CAS  Google Scholar 

  17. Kasper M, Jaks V, Hohl D, Toftgård R. Basal cell carcinoma—molecular biology and potential new therapies. J Clin Invest. 2012;122:455–63.

    Article  PubMed  CAS  Google Scholar 

  18. Mancuso M, Leonardi S, Tanori M, Pasquali E, Pierdomenico M, Rebessi S, et al. Hair cycle dependent basal cell carcinoma tumorigenesis in Ptc1neo67/+mice exposed to radiation. Cancer Res. 2006;66:6606–14.

    Article  PubMed  CAS  Google Scholar 

  19. Raasch BA, Buettner PG, Garbe C. Basal cell carcinoma: histological classification and body-site distribution. Br J Dermatol. 2006;155:401–7.

    Article  PubMed  CAS  Google Scholar 

  20. Ad Hoc Task Force, Connolly SM, Baker DR, Coldiron BM, Fazio MJ, Storrs PA, 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;67:531–50.

    Article  PubMed  Google Scholar 

  21. Narayanan K, Hadid OH, Barnes EA. Mohs micrographic surgery versus surgical excision for periocular basal cell carcinoma. Cochrane Database Syst Rev. 2012;2:CD007041.

    PubMed  Google Scholar 

  22. Mendenhall WM, Amdur RJ, Hinerman RW, Cognetta AB, Mendenhall NP. Radiotherapy for cutaneous squamous and basal cell carcinomas of the head and neck. Laryngoscope. 2009;119:1994–9.

    Article  PubMed  Google Scholar 

  23. Skiveren J, Mikkelsen MR, Daugberg H, Wulf HC. Skin reactions and quality of life after X-ray therapy of basal cell carcinoma. J Skin Cancer. 2012:825095.

  24. Wollina U, Schreiber A, Merla K, Haroske G. Combined cetuximab and volumetric arc-radiotherapy in advanced recurrent squamous cell carcinoma of the scalp. Dermatol Rep. 2011;3:e 57.

    Article  Google Scholar 

  25. Bianchi L, Orlandi A, Campione E, Angeloni C, Costanzo A, Spagnoli LG, Chimenti S. Topical treatment of basal cell carcinoma with tazarotene: a clinicopathological study on a large series of cases. Br J Dermatol. 2004;151:148–56.

    Article  PubMed  CAS  Google Scholar 

  26. Gaitanis G, Alexopoulos EC, Bassukas ID. Cryosurgery is more effective in the treatment of primary, nonsuperficial 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;21:952–8.

    PubMed  Google Scholar 

  27. Konnikov N, Avram M, Jarell A, Tannous Z. Pulsed dye laser as a novel nonsurgical treatment for basal cell carcinomas: response and follow up 12–21 months after treatment. Lasers Surg Med. 2011;43:72–8.

    Article  PubMed  Google Scholar 

  28. Lawrence CM, Haniffa M, Dahl MG. Formalin-fixed tissue Mohs surgery (slow Mohs) for basal cell carcinoma: five-year follow-up data. Br J Dermatol. 2009;160:573–80.

    Article  PubMed  CAS  Google Scholar 

  29. Mosterd K, Krekels GA, Nieman FH, Ostertag JU, Essers BA, Dirksen CD, et al. Surgical excision versus Mohs ‘micrographic surgery for primary and recurrent basal cell carcinoma of the face: a prospective randomized controlled trial with five-years’ follow-up. Lancet Oncol. 2008;9:1149–56.

    Article  PubMed  Google Scholar 

  30. Smeets NW, Krekels GA, Ostertag JU, Essers BA, Dirksen CD, Nieman FH, et al. Surgical excision vs Mohs’ micrographic surgery for basal cell carcinoma of the face: randomized controlled trial. Lancet. 2004;364:1766–72.

    Article  PubMed  Google Scholar 

  31. Daudén E; BASALE Study Group. Effectiveness and satisfaction with imiquimod for the treatment of superficial basal cell carcinoma in daily dermatological practice. J Eur Acad Dermatol Venereol. 2011;25:1304–10.

    Article  PubMed  Google Scholar 

  32. Schulze HJ, Cribier B, Requena L, Reifenberger J, Ferrándiz C, Garcia Diez A, 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;152:939–47.

    Article  PubMed  CAS  Google Scholar 

  33. 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;50:722–33.

    Article  PubMed  Google Scholar 

  34. Love WE, Bernhard JD, Bordeaux JS. Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review. Arch Dermatol. 2009;145:1431–8.

    Article  PubMed  CAS  Google Scholar 

  35. 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;47:78–82.

    Article  PubMed  CAS  Google Scholar 

  36. Kowalzick L, Rogozinski T, Wimheuer R, Pilz J, Manske U, Scholz A, et al. Intralesional recombinant interferon beta-1a in the treatment of basal cell carcinoma: results of an open-label multicentre study. Eur J Dermatol. 2002;12:558–61.

    PubMed  Google Scholar 

  37. Smucler R, Vlk M. Combination of Er:YAG laser and photodynamic therapy in the treatment of nodular basal cell carcinoma. Lasers Surg Med. 2008;40:153–8.

    Article  PubMed  Google Scholar 

  38. Souza CS, Felicio LB, Ferreira J, Kurachi C, Bentley MV, Tedesco AC, et al. Long-term follow-up of topical 5-aminolaevulinic acid photodynamic therapy diode laser single session for nonmelanoma skin cancer. Photodiagnosis Photodyn Ther. 2009;6:207–13.

    Article  PubMed  CAS  Google Scholar 

  39. Osiecka B, Jurczyszyn K, Ziółkowski P. The application of Levulan-based photodynamic therapy with imiquimod in the treatment of recurrent basal cell carcinoma. Med Sci Monit. 2012;18:I5–9.

    Article  Google Scholar 

  40. Varga E, Korom I, Raskó E, Kis E, Varga J, Oláh J, et al. Neglected basal cell carcinomas in the twenty first century. J Skin Cancer. 2011;2011:392151.

    PubMed  Google Scholar 

  41. Wollina U, Pabst F, Krönert C, Schorcht J, Haroske G, Klemm E, et al. High-risk basal cell carcinoma: an update. Expert Rev Dermatol. 2010;5:357–68.

    Article  Google Scholar 

  42. Wollina U, Helm C, Schreiber A, Brandl H-G. Extensive cranial infiltration by basal cell carcinoma. J Cutan Med Surg. 2006;10:257–8.

    PubMed  Google Scholar 

  43. Archontaki M, Stavrianos SD, Korkolis DP, Arnogiannaki N, Vassiliadis V, Liapakis IE, et al. Giant Basal cell carcinoma: clinicopathological analysis of 51 cases and review of the literature. Anticancer Res. 2009;29:2655–63.

    PubMed  Google Scholar 

  44. Wollina U, Bayyoud Y, Krönert C, Nowak A. Giant epithelial malignancies (Basal cell carcinoma, squamous cell carcinoma): a series of 20 tumors from a single center. J Cutan Aesthet Surg. 2012;5:12–9.

    Article  PubMed  Google Scholar 

  45. Lackey PL, Sargent LA, Wong L, Brzezienski M, Kennedy JW. Giant basal cell carcinoma surgical management and reconstructive challenges. Ann Plast Surg. 2007;58:250–4.

    Article  PubMed  CAS  Google Scholar 

  46. Leibovitch I, McNab A, Sullivan T, Davis G, Selva D. Orbital invasion by periocular basal cell carcinoma. Ophthalmology. 2005;112:717–23.

    Article  PubMed  Google Scholar 

  47. Kleydman Y, Manolidis S, Ratner D. Basal cell carcinoma with intracranial invasion. J Am Acad Dermatol. 2009;60:1045–9.

    Article  PubMed  Google Scholar 

  48. Guthrie TH Jr, Porubsky ES, Luxenberg MN, Shah KJ, Wurtz KL, Watson PR. Cisplatin based chemotherapy in advanced basal and squamous cell carcinomas of the skin: results in 28 patients including 13 patients receiving multimodality therapy. J Clin Oncol. 1990;8:342–6.

    PubMed  Google Scholar 

  49. Anasagasti-Angulo L, Garcia-Vega Y, Barcelona-Perez S, Lopez-Saura P, Bello-Rivero I. Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study. BMC Cancer. 2009;9:262.

    Article  PubMed  Google Scholar 

  50. Mevio N, Bertino G, Occhini A, Scelsi D, Tagliabue M, Mura F, Benazzo M. Electrochemotherapy for the treatment of recurrent head and neck cancers: preliminary results. Tumori. 2012;98:308–13.

    PubMed  Google Scholar 

  51. Wollina U, Hansel G, Koch A, Köstler E. Oral capecitabine plus subcutaneous interferon alpha in advanced squamous cell carcinoma of the skin. J Cancer Res Clin Oncol. 2005;131:300–4.

    Article  PubMed  CAS  Google Scholar 

  52. Wollina U. Cetuximab in nonmelanoma skin cancer. Expert Opin Biol Ther. 2012;12:949–56.

    Article  PubMed  CAS  Google Scholar 

  53. Kalapurakal SJ, Malone J, Robbins KT, Buescher L, Godwin J, Rao K. Cetuximab in refractory skin cancer treatment. J Cancer. 2012;3:257–61.

    Article  PubMed  CAS  Google Scholar 

  54. Caron J, Dereure O, Kerob D, Lebbe C, Guillot B. Metastatic basal cell carcinoma: report of two cases treated with cetuximab. Br J Dermatol. 2009;161:702–3.

    Article  PubMed  CAS  Google Scholar 

  55. Müller H, Eisendle K, Gastl G, Höpfl R, Zelger B. Palliative therapy of giant basal cell carcinoma with the monoclonal antiepidermal growth factor receptor antibody cetuximab. Br J Dermatol. 2008;158:1386–8.

    Article  PubMed  Google Scholar 

  56. Von Hoff DD, LoRusso PM, Rudin CM, Reddy JC, Yauch RL, Tibes R, et al. Inhibition of the hedgehog pathway in advanced basal cell carcinoma. N Engl J Med. 2009;361:1164–72.

    Article  PubMed  CAS  Google Scholar 

  57. LoRusso PM, Rudin CM, Reddy JC, Tibes R, Weiss GJ, Borad MJ, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res. 2011;17:2502–11.

    Article  PubMed  CAS  Google Scholar 

  58. Tang JY, Mackay-Wiggan JM, Aszterbaum M, Yauch RL, Lindgren J, Chang K, et al. Inhibiting the hedgehog pathway in patients with the basal cell nevus syndrome. N Engl J Med. 2012;366:2180–8.

    Article  PubMed  CAS  Google Scholar 

  59. 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;366:2717–9.

    Article  Google Scholar 

  60. Fellner C. Vismodegib (Erivedge) for advanced basal cell carcinoma. PT. 2012;37(12):670–82.

    Google Scholar 

  61. Stanton BZ, Peng LF. Small molecule modulators of the sonic hedgehog signaling pathway. Mol Biosyst. 2010;6:44–54.

    Article  PubMed  CAS  Google Scholar 

  62. Tang JY, Marghoob AA. Emerging treatments and signaling pathway inhibitors. Semin Cutan Med Surg. 2011;30(Suppl 4):14–8.

    Article  Google Scholar 

  63. Kim J, Aftab BT, Tang JY, Kim D, Lee AH, Rezaee M, et al. Itraconazole and arsenic trioxide inhibit hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists. Cancer Cell. 2013;23:23–34.

    Article  PubMed  CAS  Google Scholar 

  64. Fu J, Rodova M, Roy SK, Sharma J, Singh KP, Srivastava RK, et al. GANT-61 inhibits pancreatic cancer stem cell growth in vitro and in NOD/SCID/IL2R gamma null mice xenograft. Cancer Lett. 2013;330:22–32.

    Article  PubMed  CAS  Google Scholar 

  65. Lauth M, Bergström A, Shimokawa T, Toftgård R. Inhibition of GLI mediated transcription and tumor cell growth by small molecule antagonists. Proc Natl Acad Sci U S A. 2007;104:8455–60.

    Article  PubMed  CAS  Google Scholar 

  66. Chenna V, Hu C, Pramanik D, Aftab BT, Karikari C, Campbell NR, et al. A polymeric nanoparticle encapsulated small molecule inhibitor of hedgehog signaling (NanoHHI) bypasses secondary mutational resistance to smoothened antagonists. Mol Cancer Ther. 2012;11:165–73.

    Article  PubMed  CAS  Google Scholar 

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The authors declare that there are no actual or potential conflicts of interest in relation to this article.

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  1. Department of Dermatology and Allergology, Academic Teaching Hospital Dresden-Friedrichstadt, Friedrichstrasse 41, 01067, Dresden, Germany

    Uwe Wollina MD

  2. Policlinic for Dermatology and Venereology, University Hospital Lozenetz, Academic Educational Hospital of the Saint Kliment Ohridski University, Koiak street 1, 1407, Sofia, Bulgaria

    Georgi Tchernev MD, PhD

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Correspondence to Uwe Wollina MD.

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Wollina, U., Tchernev, G. Advanced basal cell carcinoma. Wien Med Wochenschr 163, 347–353 (2013). https://doi.org/10.1007/s10354-013-0193-5

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