Basal cell carcinoma
Basal cell carcinoma is the most commonly
diagnosed malignancy worldwide
• The annual global incidence of non-melanoma skin cancer
(NMSC) is 2–3 million cases1
• Basal cell carcinoma (BCC) constitutes ~80% of all NMSCs,
accounting for ~2 million cases worldwide each year2,3
• Basal cell carcinoma (BCC) develops in the basal layer of
the epidermis and is the most commonly diagnosed
malignancy worldwide2,4-6
• BCC is mainly a Caucasian disease. The average lifetime
risk for Caucasians to develop BCC is approximately 30%2,4
1. World Health Organization: http://www.who.int/uv/faq/skincancer/en/index1.html
2. Rubin AI et al. N Engl J Med 2005;353:2262–9
3. Diepgen TL, Mahler V. Br J Dermatol 2002;146(suppl):1–6
4. Wong CSM et al. Br Med J 2003;327:794–8
5. Roewert-Huber J et al. Br J Dermatol 2007;157:47–51
6. Lear JT et al. J R Soc Med 1998;91:585–8
2
A major cause of BCC is exposure to UV
radiation
• A major cause of BCC is exposure
to UV radiation, leading to
cumulative DNA damage and gene
mutations1–5
• Epidemiological data suggest the
overall incidence of BCC is
increasing significantly and show
marked geographical variation1,6–8
• Australia has the highest
incidence rate of BCC in the world,
reporting a rate of 1–2% per
year1,6
1. Rubin AI et al. N Engl J Med 2005;353:2262–9
2. Wong CSM et al. Br Med J 2003;327:794–8
3. Roewert-Huber J et al. Br J Dermatol 2007;157:47–51
4. Lear JT et al. J R Soc Med 1998;91:585–8
Most sporadic cases of BCC arise
from chronic sun-exposure1,2
80% occur on the head and neck
15% occur on the trunk
5% occur on the arms, legs or other sites
5. Caro I, Low JA. Clin Cancer Res 2010;16:3335–9
6. Diepgen TL, Mahler V. Br J Dermatol 2002;146(suppl):1–6
7. Ting PT et al. J Cutan Med Surg 2005;9:10–15
8. Rogers HW et al. Arch Dermatol 2010;146:283–7
3
The closer Caucasians live to the equator, the
greater the risk of developing BCC
Age-standardised rates of BCC
Country
Australia
Nambour1
Townsville1
US
New Hampshire1
Rochester, MN1
US (other)1
Europe
Finland1
The Netherlands1
Scotland (UK)1
Wales (UK)1
UK2
EASR2
WASR2
Year of report
Male
Female
1996
1998
2074
2055
1579
1195
1991
1997
1994
159
175
407
87
124
212
1999
1991
1998
2000
2003
1996–2003
1996–2003
49
46
50
128
177
104
69
45
32
37
105
148
78
53
Per 100,000 population
EASR: European age-standardised rate; WASR: World age-standardised rate
1. Diepgen TL, Mahler V. Br J Dermatol 2002;146(suppl):1–6
2. Bath-Hextall F et al. Int J Cancer 2007;121:2105–8
4
There are different clinical subtypes of BCC
• Clinical subtypes of BCCs:1–3
Nodular (60%)
•
•
Occur frequently on
sun-exposed areas of
the head
Often present as a
papule or nodule
Superficial (30%)
Other (10%)
•
Occur most frequently on
the trunk
•
Characterised by small
buds of basaloid tumour
cells extending from the
epidermis
NB: if you wish to present, reproduce or adapt the images on this slide, please seek
permission from the relevant publication house.
•
Includes pigmented BCC and
morpheaform BCC (also
called sclerosing or fibrosing
BCC)
•
Morpheaform BCCs are
aggressive infiltrating
subtypes with ill-defined
borders, making complete
excision a challenge
1. Images reproduced with permission from BMJ Publishing Group
Wong CSM et al. Br Med J 2003;327:794–8
2. Roewert-Huber J et al. Br J Dermatol 2007;157:47–51
3. Walling HW et al. Cancer Metastasis Rev 2004;23:389–402
5
Certain BCCs are associated with poorer
prognosis and a more aggressive phenotype
Prognostic factor
Tumour size
Tumour site
Definition of clinical margins
Histological subtype
Histological features of
aggression
Failure of previous treatment
Immunosuppression
Comment
Tumour size (diameter greater than 2 cm) correlates with
higher risk of recurrence and metastases1,2
Lesions on the central face, especially around the eyes,
nose, lips and ears are at higher risk of recurrence1
Poorly defined lesions are at higher risk of recurrence1
Certain subtypes confer higher risk of recurrence and
metastases1
Perineural and/or perivascular involvement confers higher
risk of recurrence1
Patients who had BCC have 10 times higher risk of
developing subsequent BCC compared to general
population2
Recurrent lesions are at a higher risk of further recurrence
and metastases1
Confers increased risk of recurrence and metastases (e.g.
recipients of solid-organ transplants)2
1. Telfer NR et al. Br J Dermatol 2008;159:35–48
2. Rubin AI et al. N Engl J Med 2005;353:2262–9
6
In some cases BCC can progress to an advanced
form
• Progression of BCC is generally characterised by slow
growth and minimal soft tissue invasiveness and
surgery cures most cases of BCC1,2
• However, BCC can develop“ into advanced BCC where
surgery is inappropriate3,4
• Advanced BCC can be disfiguring or debilitating, lead
to significant morbidity or even be fatal1,5
• Advanced BCC comprises locally advanced BCC
(laBCC) and metastatic BCC (mBCC)3
1. Walling HW et al. Cancer Metastasis Rev 2004;23:389–402
2. Lear JT et al. J R Soc Med 1998;91:585–8
3. Joshi AD, et al. J Clin Oncol 2011; 29 (Suppl: abstract e19001)
4. Tang JY, Epstein EH. AccessMedicine 2010
5. Ting PT, et al. J Cutan Med Surg 2005;9(1):10–15
7
Advanced BCC is less common but more serious
than other BCCs
Advanced BCC
• Occurs in a small proportion of patients
• Advanced BCC patients have lesions that are not appropriate for surgery, or for whom surgery would
result in substantial deformity, e.g. because of the location of the lesion

Locally advanced BCC (laBCC)

Metastatic BCC (mBCC)
Advanced BCC
mBCC
Locally advanced BCC
• Patients whose lesions are not
appropriate for surgery, or who have
medical contraindications to surgery
• Patients for whom surgery would
result in substantial morbidity and/or
deformity (e.g. invasion into skull,
limb amputation, or enucleation)
laBCC
Metastatic BCC
• Rare but serious form of BCC (0.0028–
0.55% of BCCs progress to mBCC)1
• Includes distant metastases (e.g.
bone, lung and liver) or lymph node
involvement1
• Poor prognosis (median survival: 8–14
months1-3; 5-year survival rate:
10%3,4)
BCC
1. Ting PT et al. J Cutan Med Surg 2005;9:10–15
2. von Domarus H, Stevens PJ. J Am Acad Dermatol 1984;10:1043–60
3. Lo JS et al. J Am Acad Dermatol 1991;24:715–19
4. Wong CSM et al. Br Med J 2003;327:794–8
8
Surgery is the most common treatment for
BCC, but is not always appropriate
• Surgical techniques are the most
common treatment for BCC and
have a high success rate, particularly
in uncomplicated BCC cases1,2
Surgical technique2
Surgical excision
Curettage and cautery
Cryosurgery
Mohs micrographic surgery
5-year cure rate*2
≥95%
≥95%
≥95%
~99%
NB: if you wish to present, reproduce or adapt the images on this
slide, please seek permission from the relevant publication house.
*5-year cure rate for primary BCC
• However, surgery can be debilitating and disfiguring, and is sometimes
inappropriate
Operable
Inoperable
2.
1. Walling HW et al. Cancer Metastasis Rev 2004;23:389–402
2. Image reproduced with permission from BMJ
Publishing Group. Wong CSM et al. Br Med J 2003;327:794–8
3.
4.
3. Goldberg LH et al. Arch Dermatol 2010;146:17–9 Copyright ©
2010 American Medical Association. All rights reserved
4. Von Hoff DD et al. New Engl J Med 2009;361:1164–72 Copyright
© 2009 Massachusetts Medical Society. All rights reserved
9
Current treatment options are limited for patients
with advanced BCC for whom surgery is inappropriate
• Tumours that are not appropriate for surgery, or for which surgery would
result in substantial deformity (i.e. in difficult-to-treat locations) may
require treatment with non-surgical approaches, such as:
 Radiotherapy,1 photodynamic therapy,2 chemotherapy,3 topical
therapy4,5
 Most have significant drawbacks and for many patients may not be
appropriate6,7
• For example, radiotherapy is:
 Contraindicated: in genetic syndromes predisposing to skin cancer,8,9 or
for BCC that has recurred after prior radiotherapy10
 Restricted: in tumours located near eyes or on eyelids, which are
difficult to treat,10 or in people who are nearing their maximum safe
lifetime dose of radiation11
 Generally reserved for patients ≥ 60 years, given that new skin cancers
can arise from radiotherapy scars9
1. Wong CSM et al. Br Med J 2003;327:794–8
2. Szeimies RM et al. Acta Derm Venereol 2005;85:483–90
3. Tucker SB et al. J Am Acad Dermatol 2006;54:1033–8
4. Alessi SS et al. Clinics (Sao Paulo) 2009;64:961–6
5. Gross K et al. Dermatol Surg 2007;33:433–9
6. Goppner D, Leverkus M. J Skin Cancer 2011;doi:10.1155/2011/650258
7. Von Hoff DD et al. N Engl J Med 2009;361:1164-1172
8. Loncaster J et al. Clin Oncol (R Coll Radiol) 2009;21:502–8
9. Samarasinghe V. J Skin Cancer. 2011;2011:328615
10. Telfer NR et al. Br J Dermatol 2008;159:35–48
11. Mills WA. Health Phys 1985;48:701–4
10
There is a current unmet medical need in
advanced BCC
• For patients with advanced BCC, current treatment
options are suboptimal1,2 and may add further
morbidity3,4
• At present, patients with inoperable advanced BCC or in
whom surgical resection would result in substantial
deformity have very few therapeutic options
 There is no standard therapy for advanced BCC5
• Once BCC has metastasised, it is highly malignant and has
a poor prognosis6
• Therefore, new treatment options are needed for
advanced BCC
1. Goppner D, Leverkus M. J Skin Cancer 2011; doi:10.1155/2011/650258.
2. Ting PT, et al. J Cutan Med Surg 2005;9(1):10-15
3. Wong CSM et al. Br Med J 2003;327:794–8
4. Walling HW et al. Cancer Metastasis Rev 2004;23:389–402
5. Von Hoff DD et al. New Engl J Med 2009;361:1164–72
6. Ozbek N et al. N Z Med J 2004;117:U874
11
Summary
• BCC is the most commonly diagnosed cancer and is a
mainly Caucasian disease caused by UV exposure
• Progression of BCC is generally characterised by slow
growth and minimal soft tissue invasiveness, and surgery
cures most cases of BCC
• BCC can develop into advanced BCC where surgery is
inappropriate. It can be disfiguring or debilitating, lead to
significant morbidity (locally advanced BCC) or even be
fatal (metastatic BCC)
• For patients with advanced BCC current treatment
options are suboptimal and may add further morbidity
• New treatment options are needed for advanced BCC
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References
Basal cell carcinoma
Alessi SS, et al. Treatment of cutaneous tumors with topical 5%
imiquimod cream. Clinics (Sao Paulo) 2009;64:961–966.
Bath-Hextall F, et al. Trends in incidence of skin basal cell carcinoma.
Additional evidence from a UK primary care database study. Int J
Cancer 2007;121:2105–2108.
Caro I, Low JA. The role of the hedgehog signaling pathway in the
development of basal cell carcinoma and opportunities for treatment.
Clin Cancer Res 2010;16:3335–3339.
Diepgen TL, Mahler V. The epidemiology of skin cancer. Br J Dermatol
2002;146(suppl):1–6.
Goldberg LH, et al. Basal cell nevus syndrome: a brave new world. Arch
Dermatol 2010;146:17–19.
Goppner 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.
Gross K, et al. 5% 5-Fluorouracil cream for the treatment of small
superficial Basal cell carcinoma: efficacy, tolerability, cosmetic
outcome, and patient satisfaction. Dermatol Surg 2007;33:433–439.
Joshi AD, et al. J Clin Oncol 2011; 29 (Suppl: abstract e19001).
Lear JT, et al. Basal cell carcinoma. J R Soc Med 1998;91:585–588.
Lo JS, et al. Metastatic basal cell carcinoma: report of twelve cases with
a review of the literature. J Am Acad Dermatol 1991;24:715–719.
Loncaster J, et al. Efficacy of photodynamic therapy as a treatment for
Gorlin syndrome-related basal cell carcinomas. Clin Oncol (R Coll
Radiol) 2009;21:502–508.
Mills WA. Regulatory consideration in radiation protection. Health Phys
1985;48:701–704.
Ozbek N, et al. Metastatic basal cell carcinoma. N Z Med J
2004;117:U874
Roewert-Huber J, et al. Epidemiology and aetiology of basal cell
carcinoma. Br J Dermatol 2007;157:47–51.
Rogers HW, et al. Incidence estimate of nonmelanoma skin cancer in the
United States, 2006. Arch Dermatol 2010;146:283–287.
Rubin AI, et al. Basal-cell carcinoma. N Engl J Med 2005;353:2262–2269.
Samarasinghe V. Beyond the scalpel: targeting hedgehog in skin cancer
prevention. J Skin Cancer. 2011;2011:328615.
Szeimies RM, et al. Photodynamic therapy for non-melanoma skin cancer.
Acta Derm Venereol 2005;85:483–490.
Telfer NR, et al. Guidelines for the management of basal cell carcinoma.
Br J Dermatol 2008;159:35–48.
Tang JY, Epstein EH. AccessMedicine 2010. Available from
http://www.medscape.com/viewarticle/720380 Last accessed February
2012.
Ting PT, et al. Metastatic basal cell carcinoma: report of two cases and
literature review. J Cutan Med Surg 2005;9:10–15.
Tucker SB, et al. Long-term follow-up of basal cell carcinomas treated with
perilesional interferon alfa 2b as monotherapy. J Am Acad Dermatol
2006;54:1033–1038.
von Domarus H, Stevens PJ. Metastatic basal cell carcinoma. Report of
five cases and review of 170 cases in the literature. J Am Acad Dermatol
1984;10:1043–1060.
Von Hoff DD, et al. Inhibition of the hedgehog pathway in advanced basalcell carcinoma. New Engl J Med 2009;361:1164–1172.
Walling HW, et al. Aggressive basal cell carcinoma: presentation,
pathogenesis, and management. Cancer Metastasis Rev 2004;23:389–
402.
Wong CSM, et al. Basal cell carcinoma. Br Med J 2003;327:794–798.
World Health Organization:
http://www.who.int/uv/faq/skincancer/en/index1.html Accessed
February 2012.
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