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Recent advances in treatment of non melanoma skin cancer

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Joseph L Pace MD FRCP(Edin) FRCP(Lond) F Coll Phys (Phila) FAAD

 

NON MELANOMA SKIN CANCER (NMSC)

  1. Actinic (Solar) Keratoses now considered by many authorities to represent a superficial squamous cell carcinoma
  2. Bowen’s disease
  3. Basal cell carcinoma
  4. Squamous cell carcinoma

A world wide epidemic of tsunami proportions of NMSC continues, in part due to the:

  • aging of the world’s population;
  • increased frequency of early childhood sunburns;
  • increased exposure to UV light;
  • fashion trends (arsenic has made something of a comeback being found repeatedly in some alternative medicine preparations from 3rd world countries but now also available in the West);
  • increased leisure, sun-holidays;
  • depletion of ozone layer;
  • and, more recently, immunosuppression (eg. medication following organ transplant and AIDS).

Squamous cell carcinoma has increased 30%, whilst Basal cell carcinoma have increased 75% over 10 years in South Wales. It is also likely that similar increases have occurred in other parts throughout the Western world 1

NMSC is important because of its almost exponential increase, its morbidity, and not least on account of the economic factor. Skin cancer in fact accounts for a significant portion of cost of cancer treatment.2

BREAST                                  2, 056

MELANOMA                             107

NMSC                                    529

Cost of cancer treatments in the US (1992-1995) in $ millions.

Clinical appearance

Actinic keratoses

Multiple scaly pigmented or erythematous patches on exposed areas in middle aged or elderly subjects especially those with an outdoor occupation, where the condition may occur even earlier. Actinic keratosis  may develop into invasive squamous cell carcinomas.

Bowen’s disease  

Essentially a squamous cell carcinoma in situ, often limited to a single patch of ‘eczema’ that fails to resolve with treatment.

Squamous cell carcinoma   

May follow Actinic keratosis  or Bowen’s Disease or present itself anywhere on skin/mucous membranes `with squamous epithelium. An ulcer with an indurated border may occur and causative factors also include scarring from burns, lupus erythematosus and lupus vulgaris. Certain genodermatoses such as xeroderma pigmentosum predispose to squamous cell carcinoma as also organ recipients, who have an eighteen fold risk of developing squamous cell carcinoma. Metastases from squamous cell carcinoma are rare on sun damaged skin but are an important consideration in squamous cell carcinoma on scars, mucous membranes, the lip and in organ recipients.

Basal Cell carcinoma  

Presents as a pearly nodule or ulcer on hairy skin. It does not occur on  mucus membranes or palms and soles except in the rare Gorlin syndrome.

Management

Prevention: sun avoidance from 12pm - 3pm period and protection with sun blocks and sun protective clothing.

Surgical treatment

  • Excision which is the classical procedure.
  • Moh’s surgery which is a highly effective very time consuming method of removing layer after layer and submitting to pathology immediately, with layers of skin being removed until borders are completely clear. Time factor makes it probative for most centers outside the US.

Non –surgical treatment

  • Radiotherapy
  • Cryotherapy - liquid nitrogen (-196ºC) is useful especially for smaller lesions. Can be painful and requires repeated applications.
  • Topical

5-Fluourouracil cream-works well for small superficial lesions but can cause intense inflammatory reaction for weeks and may be disliked by patients.

 

Topical nonsteroidal applications 

Published clinical trials have shown that a  topical gel containing 3% diclofenac with 2.5% hyaluronic acid may be used for treating actinic keratoses. The 2.5% hyaluronic acid (excipient) delays the transcutaneous uptake of diclofenac, leading to higher concentrations in the epidermis. Nonsteroidal anti-inflammatory drugs have activity against squamous cell carcinomas in vitro and in animal models, as well as in precursor lesions of squamous cell carcinomas.3

Imiquimod

This drug has been recently approved for the treatment of actinic keratoses and superficial basal cell carcinoma. In superficial Basal Cell carcinoma, it should be used once daily 5 days each week for 6 weeks. In nodular Basal Cell carcinoma,  good but curette lesion first ???? It also works well on all superficial lesions  but can cause  marked inflammatory reaction. 4

  • Photo dynamic therapy

Photodynamic therapy is a two step procedure involving the application, systemic or local, of a photosensitizer or its precursor and subsequent activation using illumination with visible light. Light source is an Aktilite lamp LED 16/28 Red light WL 631nm and the Photosensitiser is a Methylester of ALA (16% methyl aminolevulinate).

Following selective accumulation of photoactive porphyrins in neoplastic tissue, red light in presence of oxygen generates reactive oxygen species, which damage cellular membranes, particularly in mitochondria, and lead to cell death. Healthy surrounding tissue that has not accumulated photoactive porphyrins remains undamaged.

Photo dynamic therapy offers may advantages including its non-invasiveness and its ability to treat multiple lesions simultaneously and is, therefore, an interesting alternative for treating certain skin malignancies.

Photo dynamic therapy

Treats both Actinic Keratoses and Basal Cell Carcinomas;

Targets only diseased cells;

Non invasive, minimal scarring;

Fast healing;

Side effects minimal and transient;

High patient preference.

Photo dynamic therapy is simple to perform, is well tolerated, shows excellent clinical results and superior cosmetic outcome, and is therefore preferred by the patients. It has been available in Malta for the past 2 years. Its current use includes:  

Actinic Keratoses resistant to cryotherapy/5 FU/Imiquimod

Superficial Basal Cell Carcinomas and nodular Basal Cell Carcinomas which are difficult to treat surgically or where surgery is undesirable.

Current practice s to follow Photo dynamic therapy with Imiquimod as  a ’mopping up operation’.

-----------------------------------------------------------------------------------------

  • Oral retinoids

Useful in patients with recurrent or multiple lesions but lipid levels must be checked regularly. Not suitable for use in summer months.

 

Conclusion:

Surgery remains the gold standard of treatment but ... the possible reliable and effective non-surgical alternatives are growing fast and will become increasingly relevant and sought after in view of increasing age of patients and consequent poor anaesthetic risk, desire to avoid surgery and wish to achieve best cosmetic results.

 

References

 

  1. Holme SA, Malinovszky K, Roberts DL Changing trends in non-melanoma skin cancer in South Wales, 1988–98. British Journal of Dermatology 2000; 143:1224-9.

 

  1. Housman TS, Feldman SR, Williford PM et al. Skin cancer is among the most costly of all cancers to treat for the Medicare population. JAAD 2003; 48(3):425-9.

 

  1. Asgari M, White E, Chren MM. Nonsteroidal anti-inflammatory drug use in the prevention and treatment of squamous cell carcinoma. Dermatol Surg 2004; 30(10):1335-42.

 

  1. Gupta AK, Cherman AM, Tyring SK. Viral and Nonviral Uses of Imiquimod: A Review. J Cutan Med Surg 2004; 8(5):338-52.

 

 

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