Goda Klapatauskaitė1
1Faculty of Medicine, Vilnius University, Vilnius, Lithuania
Abstract
Background. As our population ages, the increasing incidence of non-melanoma skin cancer presents significant financial and logistical challenges. Around 90% of all cases are initiated by UV light exposure. Non-melanoma skin cancer includes squamous cell carcinoma and basal cell carcinoma, in addition to many uncommon tumors.
Aim. The aim of this article is to review and analyze scientific publications, including indications and different treatment options for non-melanoma skin cancer.
Materials and methods. A search of scientific articles was performed in PubMed, UpToDate, and Google Scholar databases using the terms “non-melanoma skin cancer”, “white skin cancer” and “management” or “treatment”. Articles were included if they were in English and no more than 10 years. Finally, 21 articles in all were analyzed.
Results. One of the most common types of cancer in the world is skin cancer, with non-melanoma skin cancer being the most common form. Management options are operative treatment, chemical destruction, physical destruction, and immunomodulatory therapy. Photodynamic treatment and several topical medications offers promise for superficial basal cell carcinoma. Nowadays photodynamic treatment provides better cosmetic results compared to surgery.
Conclusions. Non-melanoma skin cancers are generally considered treatable, but their increasing incidence has led to a growing global health problem. More and more advanced non-melanoma skin cancers are being treated with immunotherapy. Despite the development of innovative non-surgical therapies, surgical excision remains the most commonly used treatment option for non-melanoma skin cancers.
Keywords: basal cell carcinoma, squamous cell carcinoma, operative treatment, radiotherapy, cryotherapy, curettage, photodynamic treatment.
https://doi.org/10.53453/ms.2024.5.5
Non-melanoma skin cancer management - a literature review
Goda Klapatauskaitė
1
1
Faculty of Medicine, Vilnius University, Vilnius, Lithuania
Abstract
Background. As our population ages, the increasing incidence of non-melanoma skin cancer presents
significant financial and logistical challenges. Around 90% of all casesare initiated by UV light exposure. Non-
melanoma skin cancerincludes squamous cell carcinoma and basal cell carcinoma, in addition to many
uncommon tumors.
Aim. The aim of this article is to review and analyze scientific publications, including indications and different
treatment options for non-melanoma skin cancer.
Materials and methods. A search of scientific articles was performed in PubMed, UpToDate, and Google
Scholar databases using the terms “non-melanoma skin cancer”, “white skin cancer” and “management” or
“treatment”. Articles were included if they were in English and no more than 10 years. Finally, 21 articles in all
were analyzed.
Results. One of the most common types of cancer in the world is skin cancer, with non-melanoma skin cancer
being the most common form. Management options are operative treatment, chemical destruction, physical
destruction, and immunomodulatory therapy. Photodynamic treatment and several topical medications offers
promise for superficial basal cell carcinoma. Nowadays photodynamic treatment provides better cosmetic
results compared to surgery.
Conclusions. Non-melanoma skin cancers are generally considered treatable, but their increasing incidence has
led to a growing global health problem. More and more advanced non-melanoma skin cancers are being treated
with immunotherapy. Despite the development of innovative non-surgical therapies, surgical excision remains
the most commonly used treatment option for non-melanoma skin cancers.
Keywords: basal cell carcinoma, squamous cell carcinoma, operative treatment, radiotherapy, cryotherapy,
curettage, photodynamic treatment.
Journal of Medical Sciences. 5 May, 2024 - Volume 12 | Issue 3. Electronic - ISSN: 2345-0592
Medical Sciences 2024 Vol. 12 (3), p. 37-42, https://doi.org/10.53453/ms.2024.5.5
37
1. Introduction
The aging population and increased UV radiation
exposure from trips abroad and sunbed use are the
main causes of the rising prevalence. Non-
melanoma skin cancer (NMSC) encompasses a
variety of uncommon skin tumors in addition to its
primary constituents, squamous cell carcinoma
(SCC) and basal cell carcinoma (BCC). Three-
quarters of NMSC cases that are registered are
caused by BCC. In white populations, BCC is the
most prevalent type of malignant tumor .
Despite the low death rates, there is a considerable
amount of morbidity since sun-exposed areas like
the face are frequently the site of lesions . The
following are risk factors for non-melanoma skin
cancer: pale skin, genetic predisposition, residing in
high UV radiation areas, age, male sex, and prior
incidence .
2. Materials and methods
The UpToDate clinical database, Google Scholar,
and PubMed databases were searched. The search
was conducted using the phrases “non-melanoma
skin cancer” or “white skin cancer” in combination
with “management” or “treatment”. A total of 285
English-language publications were found. After an
initial title screening, 170 articles were classified as
unsuitable. Duplicate publications were also exclu-
ded. After a comprehensive review of the selected
publications, 94 more were excluded due to
inconsistencies in the subject matter, leaving a final
selection and in-depth analysis of 21 scientific
references published between 2013 and 2023. The
following sources were used: systematic literature
reviews, meta-analyses, full-text articles, and
literature reviews.
3. Results
3.1. Presentation
3.1.2 Presentation of basal cell carcinoma
The majority of BCC cases-80% on the head and
neck and 15% on the trunk occur in sun-exposed
areas . Although metastases are uncommon and
lesions grow slowly, if they are left untreated, they
may invade other structures locally and cause them
to collapse. BCC has multiple histopathological
subtypes. The pink, pearly papule with rolling
edges, telangiectasia overlaying, and sometimes
core ulceration is a typical nodular subtype.
Typically found on the trunk, superficial BCCs are
developing slowly erythematous plaques that may
appear like discoid eczema, psoriasis, or Bowen's
disease. Because morphemic BCCs appear as pale,
poorly delineated plaques, they are more invasive
and manifest later in life .
3.1.2 Presentationsquamous cell carcinoma
On sun-exposed areas, SCC can manifest as
indurated keratinising lesions or ulcers. Bowen's
disease, also known as SCC in situ, actinic
keratoses (AKs), and pre-malignant lesions can all
lead to SCC development. A sign of UV-damaged
skin, AKs develop into invasive SCC in about 1-
10% of cases . Usually, nodule, keratinising
lesions, and keratoacanthomas evolve over several
months before spontaneously inverting. Because
they are histologically identical to well-
differentiated SCCs, removal is necessary in every
instance.
3.2 Management
3.2.1 Surgery
Historically, surgery has always been the mainstay
("gold standard") of treatment. The whole tumor is
removed during surgery with the best possible
cosmetic outcome. The original tumor should be
removed in 95% of cases when well-defined, low-
risk SCCs with a diameter of less than 2 cm are
excised, maintaining a 4 mm margin. Excision with
a 4 mm margin is another successful treatment for
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primary BCC, resulting in a 5-year recurrence rate
of less than 2% . For larger and poorly
differentiated lesions, wider margins or alternative
methods of therapy are needed .
The best method for fully examining surgical
margins is micrographically controlled surgery. It is
a safe and effective way to ensure the complete
removal of invading tumors while protecting
surrounding tissue, particularly at troublesome
locations. Compared to non-surgical methods, this
provides aesthetic results that are either superior or
equivalent .
3.2.2 Physical destruction
For SCC, radiotherapy has been shown to have
cure rates as high as 90%. For primaryBCC, it has
5-year cure rates of 91.3%, while for recurrent
BCC, it has 90.2%. Radiotherapy is frequently the
chosen method of treatment for patients for whom
surgery is contraindicated, for bony or cartilaginous
sites, and when tissue preservation is crucial (lip,
lower eyelid, and inner canthus of the eye) .
Although current techniques have improved,
radiation was once a less appealing alternative for
younger people due to inferior cosmetic results.
Cryotherapy and curettage are also physically
invasive treatments that can be used to treat some
low-grade BCC and SCC. However, these methods
may not provide good cosmetic results and do not
allow for histological examination of the margins
.
3.2.3 Chemical destruction
Methyl aminolevulinate (MAL) or 5-
aminolevulinic acid is a photosensitising substance
used in topical photodynamic treatment (PDT),
which is activated by light. When malignant
keratinocytes are exposed to light, the
photosensitiser causes the production of
photoactive porphyrins, which in turn causes the
release of reactive oxygen species and the
generation of free radicals . In randomized
studies, MAL-PDT has demonstrated better clinical
and cosmetic results than cryotherapy. It is not
advised, therefore, for high-risk tumors unless the
patient refuses or is unable to get more appropriate
treatment. PDT is useful in the treatment of
premalignant lesions but is not authorized for SCC
because of the risk of metastasis and recurrence
.
Another thoroughly researched treatment for pre-
malignant lesions, AKs, Bowen's disease, and small
superficial BCCs is 5-fluorouracil (5-FU) . It is
allowed to treat sBCC with two daily applications
of the 5% formulation of the antimetabolite 5-FU
for a duration of three to six weeks . Other
topical medications that are chemically damaging
for AKs are gel diclofenac and gel ingenol
mebutate .
3.2.4 Immunomodulatory therapy
Imiquimod stimulates dendritic cells and
monocytes to produce cytokines and chemokines
by binding to toll-like receptors. Immune response
modifier imiquimod is prescribed once daily, five
times a week for six weeks to treat sBCC in
immuno-competent people . The combination
of different forms of therapy is an innovative
approach to the treatment of cancer. It is more
beneficial to use ALA-PDT with imiquimod twice a
week for 16 weeks than PDT alone . However,
the majority of studies conducted include only a
limited number of patients, the results are assessed
only clinically and without histological
confirmation. Knowledge of the molecular
mechanisms underlying PDT for the different
NMSC will improve and allow us to identify the
most promising treatment combinations .
Anti-PD1 drugs such as cemiplimab and
pembrolizumab have shown remarkable results in
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39
terms of response rate in patients with locally
advanced or metastatic SCC who are not eligible
for surgery or radiotherapy . Pembrolizumab,
an anti-PD-1 medication, was approved in 2020 for
the treatment of patients with metastatic or
recurrent SCCwho do not respond to
radiatiotherapy or curative surgery . Many
advanced-stage NMSC patients now have a better
chance of survival rates due to anti-PD-1 drugs.
Treatment of advanced disease is increasingly
dependent on immunotherapy. In order to maximize
the number of patients and achieve continuous
improvements, it is important to constantly review
the status of clinical trials .
4. Conclusions
The standard treatment for non-melanoma skin
canceris surgical excision. Other alternatives
include non-surgical techniques such as topical
chemotherapeutic agents, cryotherapy and
immunomodulatory treatment. A successful
treatment for superficial BCCis photodynamic
therapy. Response rates for nodular BCC and
Bowen's disease are satisfactor, but recurrence rates
are higher for these two NMSC subtypes. For
nodular BCC, MAL-PDT is a more effective
treatment than ALA-PDT. Numerous studies have
shown that PDT leads to better cosmetic results
than surgery. The treatment and survival of
advanced skin cancers have been transformed by
immunotherapy and targeted therapy. The selection
of patients who will benefit from these treatments
will pose new challenges in the future, regardless
of the efficacy of these new drugs.
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