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Photodynamic Therapy

Another New Light on the Horizon?

Expanding Therapeutic Options for Non Melanoma Skin Cancer

The management of damage to the skin resulting from over exposure to UV radiation and skin cancer occupies a significant proportion of our times in a Dermatology Practice . An ever increasing incidence of skin concer and it's precursor lesions, such as Keratosis combined with am increased awareness of the problem by the public results in a rising demand for more effective therapies. As lesions often affect the face, patients expert a practical treatment which offers good clearance, but wish for the possible cosmetic outcome. Topical Photodynamic Therapy (PDT) promises to be an effetive alternative to surgery and other destructive therapies in certain non-melanoma skin cancers.

Why Should Actinic Keratoses be Treated?

Actinic Keratoses (AK) is a common condition particularly in the elderly and in patients who live in geographically sunny locations. Up to 40% of Squamous cell carcinomas arise from AK and current data suggests that 1 and 1000 cases AK will progress to SCC. Therefore successful treatment of AK may reduce the incidence of SCC in particular of one takes into account that our average patient has not got one but multiple if not hundreds of AK's. Futhermore is has been shown that as much as 50% of hyperkeratotic AK's on the hands may progress to a SCC. However, one should not forget that most lesions occur on cosmetically sensitive sites such as the face and current treatments may leave scars or hypo pigmentation.

What About the Non Melanoma Skin Cancers (NMSC)

Melanoma and Non Melanoma skin cancer (Basal and squamous cell carcinoma) are now the most common type of skin cancer in the Caucasion population and the incidence of skin cancer has reached epidermic proportions. Although it is difficult to determine exact incidence data because cancer registers exclude NMSC's it is estimated that there is an increase in incidence of 3 to 8% per year for NMSC (and 3 to 7% for melanomas!). The rising incidence rate of NMSC is probably due to a combination of increased outdoor activities, changes in clothing style, increases longevity and ozone depletion. Early diagnosis and treatment are needed to decrease the number of deaths due to skin cancer since prognosis improves when lesions are detected early for both melanoma and NMSC.

So What Can We Do?

Various options exists for managing AK's and NMSC's and clinicians may consider several factors to determine the most appropriate management strategy including size, location, growth pattern as well as patient preference and medical history. Common treatments include cry therapy with liquid nitrogen, curettage, excision, topical treatment (i.e 5FU, imiquimod) chemical peels, laser therapy (CO2 - laser) and now: photodynamic therapy.

How Does PDT Works?

Photodynamic therapy is a two step process involving the application of a topical light sensitive substance followed by activation of this substance through illumination with a proprietary light source. Commercial agent used at present are 5-Aminolevulanic Acid (ALA) and Methyl-Aminolevulanic. ALA and it's esters accumulate photo active porphyrins (PAP) in neoplastic tissue. Exposure to red light in the presence of oxygen reactive oxygen which damages cellular membrane, particularly in the mitochondria leading to selective cell death.

Healthy surrounding tissue which has not accumulated porphyrins is left undamaged. After 2 to 3 weeks the lesion is replaced by new and healthy tissue. Repeat treatments are possible if required to optimise success.

How Does PDT Compared to Conventional Therapy?

Therapy Advantages Disadvantages
ALA 
or 
PDT
  • High response rate
  • Simultaneous treatment of multiple AK's
  • Standardised treatment
  • Rapid healing
  • Two stage process
  • Subjective pain
  • Light source necessary for PDT
Cryotherapy
  • High response rate
  • Painful blistering
  • Pigmentation effects
  • No standardisation concerning length and depth of freezing
  • Risk of scarring
  • Limited number of AK's to be treated
Electrodeiccation
  • High response rate
  • Local anesthesia required
  • Superficial scarring
  • Only suitable for single lesions
Topical 5-Flurouracil
  • High response rate (but High recurrence rate)
  • Treatment of large areas of skin possible
  • Time-consuming (approx 4 weeks)
  • Low patient
  • Risk of systemic 5-fluorouracil exposition when occluded

The Procedure

Firstly scales and crusts are removed and the ALA or ALA ester is applied to all lesions plus a small surrounding area and then covered by an occlusive dressing for 3 to 4 hours. The dressing is removed, excess cream is wiped off and the area is immediately exposed to red light of 635nm with a total light dose of 80J/cm.

Multiple lesions can be treated during the same treatment session. Extend of the lesions can be clearly demonstrated by the use of a wool light which shows bright red florescence where the pophrins have accumulated. The duration of the illumination is between 8 to 16 minutes depending on the light source used. The procedure is relatively painful in particular during the light exposure and depending on the number of lesions. Usually pain control is achieved by administrations 2 Stopayne capsules half an hour before treatment and analgesics might be necessary for the first 24 hours. The treatment area is left open and Bactroban is applied only if the area is oozing. Directly after the illumination there will be some erythematic and edema, oozing, crusting and scabbing might occur during the follwoing 24 hours the area should be kept moist either with frequent application of aqueous cream or Vaseline. It is best compared to the afercare of a rather severe sunburn. Complete healing usually takes place within a week or two. The cosmetic result is excellent, and although patients complain about the pain and the sometimes rather drastic looks of the tissue destruction during the first week there is a very high patient satisfaction concerning the final outcome.

So in summary; PDT is quite a noval treatment for non melanoma skin cancer. It is effective and has several benefits conventional treatment approaches.

  • It is a effective as surgery but superior to cryotherapy
  • It is selective for cancerous tissue
  • It is non invasive and non scarring
  • It can be used repeatedly if necessary
  • Cosmetic results are superior to all comparable treatments

And patients often prefer it to surgery, cryosurgery of 5FU. Whether it will be used widely will depend largely on the costs of the treatment. One has to take the cost of the light source as well as the cost for the cream into account and it is expensive if used for AK's and costs being compared to cryotherapy. However if used for superficial BCC's and the costs will be compared to surgery it could become a cost effective treatment. What it certainly does is offering an additional choice for treating a condition which is of ever increaseing importance in the daily Dermatology practice.