Aktuelles Management des Basalzellkarzinoms

Zusammenfassung

Ziel der Studie Der aktuelle Standard von Diagnostik und Therapie des Basalzellkarzinoms soll dargestellt werden. Hieraus sollen sinnvolle Vorgehensweisen für das klinische Management abgeleitet werden.

Methodik Es erfolgte eine systematische Literaturrecherche in der Online-Datenbank PubMed. Die gesammelten Informationen wurden analysiert und bewertet. Aus den gewonnenen Erkenntnissen wurde ein Gesamtkonzept erstellt.

Ergebnisse Das Basalzellkarzinom ist der häufigste Tumor des Menschen und die Inzidenz wird voraussichtlich künftig weiter zunehmen. Beim Management der Erkrankung wird eine eindimensionale Orientierung am klinischen bzw. histologischen Basalzellkarzinom-Subtyp der Heterogenität des Tumors nicht gerecht. Zunehmende Bedeutung gewinnt die primäre Durchführung einer Risikostratifizierung, die für die weiteren diagnostischen und therapeutischen Schritte maßgeblich ist. Goldstandard in der Behandlung bleibt weiterhin das operative Vorgehen, welches möglichst mittels mikrografisch kontrollierter Chirurgie erfolgen sollte. Daneben existieren weitere Therapieverfahren wie die Radiotherapie oder eine Reihe an topischen Therapieoptionen (photodynamische Therapie, Kryotherapie oder Applikation von 5-Fluoruracil bzw. Imiquimod), die in bestimmten Fällen zur Anwendung kommen können. Auch für fortgeschrittene oder metastasierte Basalzellkarzinome stehen mit den Hedgehog-Inhibitoren wirksame Medikamente zur Verfügung, für die inzwischen eine mehrjährige Anwendungserfahrung hinsichtlich Wirksamkeit und Umgang mit unerwünschten Ereignissen vorliegt. Mit den PD-1-Inhibitoren steht eine weitere systemische Therapieoption in Aussicht, deren Nutzen aktuell noch in klinischen Studien überprüft wird.

Schlussfolgerung Das Basalzellkarzinom wird in den kommenden Jahren weiter an Relevanz in der täglichen dermatologischen Praxis gewinnen. Eine strukturierte Herangehensweise zur Einschätzung der vorliegenden Risikokategorie des Tumors und die anschließende Festlegung des optimalen Therapieregimes sind von zentraler Bedeutung. Fortgeschrittene oder metastasierte Tumoren stellen keine aussichtslose Situation für den Patienten mehr dar. Durch adaptierte Dosierschemata kann ein nebenwirkungsbedingter Therapieabbruch unter langfristiger Hedgehog-Therapie vermieden werden. Das therapeutische Potenzial von PD-1-Inhibitoren könnte bald auch beim Basalzellkarzinom genutzt werden.

Abstract

Aim of study We present the current standard in diagnosis and treatment of basal cell carcinoma. Useful procedures for clinical management should be derived from this.

Methods A systematic literature search was carried out in the PubMed online database. The collected information was analyzed and evaluated. An overall concept was created from the gained knowledge.

Results Basal cell carcinoma is the most common tumor in humans and its incidence is expected to increase in the future. When managing the disease, a one-dimensional orientation towards the clinical or histological subtype is not sufficient because of the heterogeneity of the tumor. The primary implementation of risk stratification, which is decisive for the further diagnostic and therapeutic steps, is becoming increasingly important. The gold standard in treatment continues to be the surgical procedure, which should be carried out using micrographically controlled surgery if possible. In addition, there are other therapeutic methods such as radiotherapy or a number of topical therapy options (photodynamic therapy, cryotherapy, application of 5-fluorouracil or imiquimod), which can be used in certain cases. Hedgehog inhibitors are also effective drugs for advanced or metastatic basal cell carcinoma. Practitioners have gained several years of experience with regard to effectiveness and handling of adverse events. With the PD-1 inhibitors, another systemic therapy option is on the horizon, but the benefit is currently still being tested in clinical studies.

Conclusion Basal cell carcinoma will continue to gain in relevance in daily dermatological practice in the coming years. A structured approach to the assessment of the existing risk category of the tumor and the subsequent determination of the optimal therapy regimen are of central importance. Advanced or metastatic tumors no longer represent a hopeless situation for the patient. With long-term hedgehog therapy, an adapted dosage scheme can avoid discontinuation of therapy due to side effects. The therapeutic potential of PD-1 inhibitors could soon also be used in treating basal cell carcinoma.

Publication History

Article published online:
22 December 2021

• Literatur

• 1 Peterson SC, Eberl M, Vagnozzi AN. et al. Basal cell carcinoma preferentially arises from stem cells within hair follicle and mechanosensory niches. Cell Stem Cell 2015; 16: 400-412 DOI: 10.1016/j.stem.2015.02.006.
• 2 Youssef KK, Van Keymeulen A, Lapouge G. et al. Identification of the cell lineage at the origin of basal cell carcinoma. Nat Cell Biol 2010; 12: 299-305 DOI: 10.1038/ncb2031.
• 3 Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma. N Engl J Med 2005; 353: 2262-2269 DOI: 10.1056/NEJMra044151.
• 4 Lomas A, Leonardi-Bee J, Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol 2012; 166: 1069-1080 DOI: 10.1111/j.1365-2133.2012.10830.x.
• 5 Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. und Zentrum für Krebsregisterdaten (edss). Krebs in Deutschland für 2015/2016. 12. Ausgabe. Berlin: Robert-Koch-Institut; 2019: 68-69
• 6 Eisemann N, Jansen L, Castro FA. et al., GEKID Cancer Survival Working Group. Survival with nonmelanoma skin cancer in Germany. Br J Dermatol 2016; 174: 778-785 DOI: 10.1111/bjd.14352.
• 7 Kricker A, Armstrong BK, English DR. et al. Does intermittent sun exposure cause basal cell carcinoma? A case-control study in Western Australia. . Int J Cancer 1995; 60: 489-494 DOI: 10.1002/ijc.2910600411.
• 8 Kricker A, Weber M, Sitas F. et al. Early Life UV and Risk of Basal and Squamous Cell Carcinoma in New South Wales, Australia. Photochem Photobiol 2017; 93: 1483-1491 DOI: 10.1111/php.12807.
• 9 Lang BM, Balermpas P, Bauer A. et al. S2k-Leitlinie Basalzellkarzinom der Haut – Teil 1: Epidemiologie, Genetik und Diagnostik. J Dtsch Dermatol Ges 2019; 17: 94-104 DOI: 10.1111/ddg.13733_g.
• 10 Krynitz B, Olsson H, Lundh Rozell B. et al. Risk of basal cell carcinoma in Swedish organ transplant recipients: a population-based study. Br J Dermatol 2016; 174: 95-103 DOI: 10.1111/bjd.14153.
• 11 Bonilla X, Parmentier L, King B. et al. Genomic analysis identifies new drivers and progression pathways in skin basal cell carcinoma. Nat Genet 2016; 48: 398-406 DOI: 10.1038/ng.3525.
• 12 Al Sabbagh MM, Baqi MA. Bazex-Dupré-Christol syndrome: review of clinical and molecular aspects. Int J Dermatol 2018; 57: 1102-1106 DOI: 10.1111/ijd.14065.
• 13 Bal E, Park HS, Belaid-Choucair Z. et al. Mutations in ACTRT1 and its enhancer RNA elements lead to aberrant activation of Hedgehog signaling in inherited and sporadic basal cell carcinomas. Nat Med 2017; 23: 1226-1233 DOI: 10.1038/nm.4368.
• 14 Michaelsson G, Olsson E, Westermark P. The Rombo syndrome: a familial disorder with vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, basal cell carcinomas and peripheral vasodilation with cyanosis. Acta Derm Venereol 1981; 61: 497-503
• 15 Kossard S, Epstein EH, Cerio J. et al. Basal cell carcinoma. In: LeBoit PE, Burg G, Weedon D, Sarasin A. Skin Tumours: Pathology and Genetics. World Health Organization Classification of Tumours. Lyon, Frankreich: IARC Press; 2006: 13-20
• 16 Bichakjian CK, Olencki T, Aasi SZ. et al. Basal Cell Skin Cancer, Version 1. 2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2016; 14: 574-597 DOI: 10.6004/jnccn.2016.0065.
• 17 Peris K, Fargnoli MC, Garbe C. et al. Diagnosis and treatment of basal cell carcinoma: European consensus-based interdisciplinary guidelines. Eur J Cancer 2019; 118: 10-34 DOI: 10.1016/j.ejca.2019.06.003.
• 18 Ahnlide I, Zalaudek I, Nilsson F. et al. Preoperative prediction of histopathological outcome in basal cell carcinoma: flat surface and multiple small erosions predict superficial basal cell carcinoma in lighter skin types. Br J Dermatol 2016; 175: 751-761 DOI: 10.1111/bjd.14499.
• 19 Kittler H, Marghoob AA, Argenziano G. et al. Standardization of terminology in dermoscopy/dermatoscopy: results of the third consensus conference of the International Society of Dermoscopy. J Am Acad Dermatol 2016; 74: 1093-1106 DOI: 10.1016/j.jaad.2015.12.038.
• 20 Ulrich M, von Braunmuehl T, Kurzen H. et al. The sensitivity and specificity of optical coherence tomography for the assisted diagnosis of nonpigmented basal cell carcnoma: an observational study. Br J Dermatol 2015; 173: 428-435 DOI: 10.1111/bjd.13853.
• 21 Ferrante di Ruffano L, Dinnes J, Deeks JJ. et al., Cochrane skin cancer diagnostic test accuracy group. Optical coherence tomography for diagnosing skin cancer in adults. Cochrane Database Syst Rev 2018; 12: CD013189 DOI: 10.1002/14651858.CD013189.
• 22 Edwards SJ, Osei-Assibey G, Patalay R. et al. Diagnostic accuracy of reflectance confocal microscopy using VivaScope for detecting and monitoring skin lesions: a systematic review. Clin Exp Dermatol 2017; 42: 266-275 DOI: 10.1111/ced.13055.
• 23 Seidenari S, Arginelli F, Bassoli S. et al. Diagnosis of BCC by multiphoton laser tomography. Skin Res Technol 2013; 19: 297-304 DOI: 10.1111/j.1600-0846.2012.00643.x.
• 24 Abramson AK, Krasny MJ, Goldman GD. Tangential shave removal of basal cell carcinoma. Dermatol Surg 2013; 3: 387-392 DOI: 10.1111/dsu.12106.
• 25 Kauvar AN, Cronin T, Roenigk R. et al. Consensus for nonmelanoma skin cancer treatment: basal cell carcinoma, including a cost analysis of treatment methods. Dermatol Surg 2015; 41: 550-571 DOI: 10.1097/DSS.0000000000000296.
• 26 Jansen MHE, Mosterd K, Arits AHMM. et al. Five-Year Results of a Randomized Controlled Trial Comparing Effectiveness of Photodynamic Therapy, Topical Imiquimod, and Topical 5-Fluorouracil in Patients with Superficial Basal Cell Carcinoma. J Invest Dermatol 2018; 138: 527-533 DOI: 10.1016/j.jid.2017.09.033.
• 27 Geisse J, Caro I, Lindholm J. et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehiclecontrolled studies. J Am Acad Dermatol 2004; 50: 722-733 DOI: 10.1016/j.jaad.2003.11.066.
• 28 Wiegell SR, Skodt V, Wulf HC. Daylight-mediated photodynamic therapy of basal cell carcinomas-an explorative study. J Eur Acad Dermatol Venereol 2014; 28: 169-175 DOI: 10.1111/jdv.12076.
• 29 Ferrara F, Lacava R, Barisani A. et al. Combined CO2 laser and photodynamic therapy enhances the efficacy of treatment of basal cell carcinomas. J Dtsch Dermatol Ges 2019; 17: 1251-1256 DOI: 10.1111/ddg.14004.
• 30 Har-Shai Y, Sommer A, Gil T. et al. Intralesional cryosurgery for the treatment of basal cell carcinoma of the lower extremities in elderly subjects: a feasibility study. Int J Dermatol 2016; 55: 342-350 DOI: 10.1111/ijd.13168.
• 31 Cho M, Gordon L, Rembielak A. et al. Utility of radiotherapy for treatment of basal cell carcinoma: a review. Br J Dermatol 2014; 171: 968-973 DOI: 10.1111/bjd.13253.
• 32 Sekulic A, Migden MR, Oro AE. et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012; 366: 2171-2179 DOI: 10.1056/NEJMoa1113713.
• 33 Sekulic A, Migden MR, Basset-Seguin N. et al. ERIVANCE BCC Investigators. Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study. BMS Cancer 2017; 17: 332 DOI: 10.1186/s12885-017-3286-5.
• 34 Basset-Séguin N, Hauschild A, Kunstfeld R. et al. Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, openlabel trial. Eur J Cancer 2017; 86: 334-348 DOI: 10.1016/j.ejca.2017.08.022.
• 35 Migden MR, Guminski A, Gutzmer R. et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol 2015; 16: 716-728 DOI: 10.1016/S1470-2045(15)70100-2.
• 36 Dummer R, Guminksi A, Gutzmer R. et al. Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II randomized, double-blind BOLT study. Br J Dermatol 2020; 182: 1369-1378 DOI: 10.1111/bjd.18552.
• 37 Lacouture ME, Dréno B, Ascierto PA. et al. Characterization and management of hedgehog pathway inhibitor-related adverse events in patients with advanced basal cell carcinoma. Oncologist 2016; 21: 1218-1229 DOI: 10.1634/theoncologist.2016-0186.
• 38 Dréno B, Kunstfeld R, Hauschild A. et al. Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimencontrolled, double-blind, phase 2 trial. Lancet Oncol 2017; 18: 404-412 DOI: 10.1016/S1470-2045(17)30072-4.
• 39 Woltsche N, Pichler N, Wolf I. et al. Managing adverse effects by dose reduction during routine treatment of locally advanced basal cell carcinoma with the hedgehog inhibitor vismodegib: a single centre experience. J Eur Acad Dermatol Venereol 2019; 33: 144-145 DOI: 10.1111/jdv.15367.
• 40 Mortier L, Bertrand N, Basset-Seguin N. et al. Vismodegib in neoadjuvant treatment of locally advanced basal cell carcinoma: First results of a multicenter, open-label, phase 2 trial (VISMONEO study). Journal of Clinical Oncolog 2018; 36: 9509-9509 DOI: 10.1200/JCO.2018.36.15_suppl.9509.
• 41 Borradori L, Sutton B, Shayesteh P. et al. Rescue therapy with anti-programmed cell death protein 1 inhibitors of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in five cases. Br J Dermatol 2016; 175: 1382-1386 DOI: 10.1111/bjd.14642.
• 42 Falchook GS, Leidner R, Stankevich E. et al. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer 2016; 4: 70 DOI: 10.1186/s40425-016-0176-3.
• 43 Peris K, Tambone S, Kostaki D. et al. Treatments of advanced basal cell carcinoma: a review of the literature. G Ital Dermatol Venereol 2016; 151: 77-86
• 44 Chen AC, Martin AJ, Choy B. et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med 2015; 373: 1618-1261 DOI: 10.1056/NEJMoa1506197.
• 45 Muranushi C, Olsen CM, Green AC. et al. Can oral nonsteroidal antiinflammatory drugs play a role in the prevention of basal cell carcinoma? A systematic review and metaanalysis. . J Am Acad Dermatol 2016; 74: 108-119 DOI: 10.1016/j.jaad.2015.08.034.
• 46 Flohil SC, van der Leest RJ, Arends LR. et al. Risk of subsequent cutaneous malignancy in patients with prior keratinocyte carcinoma: a systematic review and meta-analysis. Eur J Cancer 2013; 49: 2365-2375 DOI: 10.1016/j.ejca.2013.03.010.
• 47 Lang BM, Balermpas P, Bauer A. et al. S2k-Leitlinie Basalzellkarzinom der Haut - Teil 2: Therapie, Prävention und Nachsorge. J Dtsch Dermatol Ges 2019; 17: 214-231 DOI: 10.1111/ddg.13755_g. PMID: 30762951