Elsevier

European Journal of Cancer

Volume 118, September 2019, Pages 10-34
European Journal of Cancer

Original Research
Diagnosis and treatment of basal cell carcinoma: European consensus–based interdisciplinary guidelines

https://doi.org/10.1016/j.ejca.2019.06.003Get rights and content

Highlights

  • Basal cell carcinoma (BCC) is the most common epithelial malignant tumour in white populations.

  • A new classification into “easy-to-treat” (common) BCC and “difficult-to-treat” BCC is proposed.

  • Surgery is the first-line therapy in all types of BCCs.

  • Treatment choice for advanced BCC should be discussed by a multidisciplinary tumour board.

  • Hedgehog inhibitors are used in "difficult-to-treat" BCC, and immunotherapy is a promising treatment under investigation.

Abstract

Basal cell carcinoma (BCC) is the most common malignant tumour in white populations. Multidisciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer collaborated to develop recommendations on diagnosis and treatment of BCC. A new classification into ‘easy-to-treat (common) BCC and ‘difficult-to-treat’ BCC is proposed. Diagnosis is based on clinicodermatoscopic features for ‘easy-to-treat’ BCCs. Histopathological confirmation is mandatory in ambiguous lesions and in BCCs located in high-risk areas. The first-line treatment of ‘easy-to-treat’ BCC is complete surgery. Microscopically controlled surgery shall be offered for high-risk BCC, recurrent BCC and BCC in critical anatomical sites. Topical therapies (5% imiquimod, 5% fluorouracil) and destructive approaches (curettage, electrocautery, cryotherapy, laser ablation) should be considered in patients with low-risk superficial BCC. Photodynamic therapy is an effective treatment for superficial BCC and thin nodular BCC. The therapy for a ‘difficult-to-treat’ BCC should preferentially be discussed by a multidisciplinary tumour board. Hedgehog inhibitors, vismodegib or sonidegib, should be offered to patients with locally advanced and metastatic BCCs. Immunotherapy with anti–programmed cell death 1 (PD-1) antibodies is a promising therapeutic option, currently being investigated in clinical trials. Radiotherapy represents a valid alternative to surgery for BCC on the face, especially in elderly patients. In patients with naevoid basal cell carcinoma syndrome (NBCCS), close surveillance and regular skin examinations are required to diagnose and treat BCCs at early stage. Long-term follow-up is recommended in patients with high-risk BCC subtypes, high-risk sites, multiple BCCs and NBCCS.

Section snippets

Societies in charge

These guidelines were developed on behalf of the European Dermatology Forum (EDF), as decided at the EDF meeting in January 2017. The European Association of Dermato-Oncology (EADO) coordinated the authors’ contributions within its Guideline Program in Oncology (GPO). The responsible editor is Jean Jacques Grob (senior author), and the coordinator of the guideline is Ketty Peris (first author). To guarantee the interdisciplinary character of these guidelines, they were developed in cooperation

Primary therapy

Most primary BCCs can be easily treated by surgery or by non-surgical methods for certain subtypes. BCCs with high risk of recurrence need to be treated more aggressively. Risk of recurrences increases with tumour size, poorly defined margins, aggressive histological subtype or previous recurrences. Certain tumours can be locally advanced with destruction of adjacent tissues or difficult to treat for other reasons which might need discussion regarding appropriate therapy in a multidisciplinary

When should we still consider surgery for difficult-to-treat BCC?

Surgery can be considered as a primary therapeutic option, as a palliative option and also following a neoadjuvant approach attempting to reduce the extent of the surgical procedure. The appropriate management should be carefully planned in a skin cancer multidisciplinary board wherein the potential strategies on surgical excision, reconstruction, tissue preservation, indications for prosthesis and radiotherapy are discussed. Appropriate imaging to determine the extent of the tumour is

Radiotherapy of BCC

During recent decades, radiotherapy has been reported as a valid alternative to surgery. The risk of developing a radiotherapy-induced secondary skin cancer is negligible using required radiation doses to treat cutaneous carcinomas. In contrast, a high risk exists in patients treated with lower doses for benign cutaneous conditions [121], [122].

Follow-up

Follow-up should be performed in patients with BCC because of risk of local recurrence (treatment failure), subsequent BCC development (metachronous BCCs) and increased risk of development of other skin cancers (SCC and melanoma) [1], [29], [48].

Diagnosis and management of patients with naevoid basal cell carcinoma syndrome

NBCCS is a rare, autosomal dominant familial cancer syndrome with a high degree of penetrance and variable expression. Its prevalence is estimated at 1 per 40.000–60.000 persons. NBCCS is caused by mutations in the PTCH1 gene, with de novo mutations occurring in about 20%–30% of patients, and more rarely by mutations in SMO, SUFU and PTCH2 [135].

Information for patients

When diagnosing BCC, it is important to explain to patients that these tumours are only locally invasive and will not have any detrimental effects on survival unless in rare high-risk or advanced cases. Even though most tumours are growing slowly, the potential consequences of foregoing treatment should be explained. There may be a need to discuss surgery-associated morbidity as the psychological impact of disfiguring surgery cannot be underestimated. The patient should always be offered

Funding

None.

Conflict of interest statement

K.P. reports grants and personal fees from Almirall and AbbVie, during the conduct of the study, and personal fees from Biogen, Lilly, Celgene, Galderma, Leo Pharma, Novartis, Pierre Fabre, Sanofi, Sandoz, Sun Pharma and Janssen, outside the submitted work. M.C.F. reports personal fees from Roche and Mylan; grants and personal fees from Galderma, during the conduct of the study; grants and personal fees from AbbVie, Almirall, Leo Pharma, Novartis, Sanofi and Union Chimique Belge (UCB); and

References (144)

  • A. Lallas et al.

    Accuracy of dermatoscopic criteria for discriminating superficial from other subtypes of basal cell carcinoma

    J Am Acad Dermatol

    (2014)
  • H. Kittler 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)
  • D. Altamura et al.

    Dermoscopy of basal cell carcinoma: morphologic variability of global and local features and accuracy of diagnosis

    J Am Acad Dermatol

    (2010)
  • S.K.T. Que

    Research techniques made simple: noninvasive imaging Technologies for the Delineation of basal cell carcinomas

    J Invest Dermatol

    (2016)
  • E. van Loo et al.

    Surgical excision versus Mohs' micrographic surgery for basal cell carcinoma of the face: a randomised clinical trial with 10 year follow-up

    Eur J Cancer

    (2014)
  • R.A. Wain et al.

    Reconstructive outcomes of Mohs surgery compared with conventional excision: a 13-month prospective study

    J Plast Reconstr Aesthet Surg

    (2015)
  • S.M. Connolly et al.

    AAD/ACMS/ASDSA/ASMS 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)
  • D. Masud et al.

    Basal cell carcinomata: risk factors for incomplete excision and results of re-excision

    J Plast Reconstr Aesthet Surg

    (2016)
  • J. Angulo et al.

    Mohs micrographic surgery for repeat excision of basal cell carcinomas on the head with positive margins

    Actas Dermosifiliogr

    (2011)
  • A.H. Arits 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)
  • M.H. Roozeboom et al.

    Three-year follow-up results of photodynamic therapy vs. Imiquimod vs. Fluorouracil for treatment of superficial basal cell carcinoma: a single-blind, noninferiority, randomized controlled trial

    J Invest Dermatol

    (2016)
  • M.H.E. Jansen 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)
  • M.H. Roozeboom et al.

    Tumor thickness and adnexal extension of superficial basal cell carcinoma (sBCC) as determinants of treatment failure for methylaminolevulinate (MAL)-photodynamic therapy (PDT), imiquimod, and 5-fluorouracil (FU)

    J Am Acad Dermatol

    (2015)
  • F. Bath-Hextall et al.

    Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial

    Lancet Oncol

    (2014)
  • H.C. Williams et al.

    Surgery versus imiquimod for nodular and superficial basal cell carcinoma (SINS) study group. Surgery versus 5% imiquimod for nodular and superficial basal cell carcinoma: 5-year results of the SINS randomized controlled trial

    J Invest Dermatol

    (2017)
  • T. Rodriguez-Vigil et al.

    Recurrence rates of primary basal cell carcinoma in facial risk areas treated with curettage and electrodesiccation

    J Am Acad Dermatol

    (2007)
  • M. Haedersdal et al.

    Translational medicine in the field of ablative fractional laser (AFXL)-assisted drug delivery: a critical review from basics to current clinical status

    J Am Acad Dermatol

    (2016)
  • M.H. Roozeboom et al.

    Fractionated 5-aminolevulinic acid photodynamic therapy after partial debulking versus surgical excision for nodular basal cell carcinoma: a randomized controlled trial with at least 5-year follow-up

    J Am Acad Dermatol

    (2013)
  • J. Loncaster et al.

    Efficacy of photodynamic therapy as a treatment for Gorlin Syndrome-related basal cell carcinomas

    Clin Oncol

    (2009)
  • M. Trakatelli et al.

    Update of the European guidelines for basal cell carcinoma management

    Eur J Dermatol

    (2014)
  • A. Hauschild et al.

    Brief S2k guidelines--Basal cell carcinoma of the skin

    J Dtsch Dermatol Ges

    (2013)
  • M. Dandurand et al.

    Management of basal cell carcinoma in adults Clinical practice guidelines

    Eur J Dermatol

    (2006)
  • N.R. Telfer et al.

    Guidelines for the management of basal cell carcinoma

    Br J Dermatol

    (2008)
  • K.K. Youssef et al.

    Identification of the cell lineage at the origin of basal cell carcinoma

    Nat Cell Biol

    (2010)
  • C. Pellegrini et al.

    Understanding the molecular genetics of basal cell carcinoma

    Int J Mol Sci

    (2017)
  • R.L. Yauch et al.

    Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma

    Science

    (2009)
  • J. Lehmann et al.

    Xeroderma pigmentosum - facts and perspectives

    Anticancer Res

    (2018)
  • E. Bal et al.

    Mutations in ACTRT1 and its enhancer RNA elements lead to aberrant activation of Hedgehog signaling in inherited and sporadic basal cell carcinomas

    Nature Med

    (2017)
  • C. Dessinioti et al.

    Basal cell carcinoma: what's new under the sun

    Photochem Photobiol

    (2010)
  • M.P. Staples et al.

    Non-melanoma skin cancer in Australia: the 2002 national survey and trends since 1985

    Med J Aust

    (2006)
  • A.S. Holm et al.

    Basal cell carcinoma is as common as the sum of all other cancers: implications for treatment capacity

    Acta Derm Venereol

    (2016)
  • A. Lomas et al.

    A systematic review of worldwide incidence of nonmelanoma skin cancer

    Br J Dermatol

    (2012)
  • T.W. Lucke et al.

    An audit of the completeness of non-melanoma skin cancer registration in Greater Glasgow

    Br J Dermatol

    (1997)
  • D.H. Brewster et al.

    Recent trends in incidence of nonmelanoma skin cancers in the East of Scotland, 1992-2003

    Br J Dermatol

    (2007)
  • S. Boi et al.

    Epidemiology of skin tumors: data from the cutaneous cancer registry in Trentino, Italy

    J Cutan Med Surg

    (2003)
  • C. Rudolph et al.

    Incidence trends of nonmelanoma skin cancer in Germany from 1998 to 2010

    J Dtsch Dermatol Ges

    (2015)
  • N. Eisemann et al.

    Survival with nonmelanoma skin cancer in Germany

    Br J Dermatol

    (2016)
  • G. Goldenberg et al.

    Incidence and prevalence of basal cell carcinoma (BCC) and locally advanced BCC (LABCC) in a large commercially insured population in the United States: a retrospective cohort study

    J Am Acad Dermatol

    (2016)
  • S. Dacosta Byfield et al.

    Age distribution of patients with advanced non-melanoma skin cancer in the United States

    Arch Dermatol Res

    (2013)
  • J.Y.S. Kim et al.

    Guidelines of care for the management of basal cell carcinoma

    J Am Acad Dermatol

    (2018)
  • Cited by (348)

    • Extensive head and neck skin cancers: Carcinologic surgery as a cornerstone of treatment

      2024, Journal of Stomatology, Oral and Maxillofacial Surgery
    View all citing articles on Scopus
    1

    Contributed equally.

    View full text