Photodynamic therapy (PDT) involves the use of light to activate a photosensitiser that is localised in diseased tissues, resulting in the formation of cytotoxic reactive oxygen species. Light sources include high-intensity lamps, lasers and, more recently, daylight.
Topical PDT is a non-invasive treatment option for some patients with actinic keratoses (AKs), Bowen’s diseasecSCC in situ (also known as intra-epidermal SCC), and superficial and thin basal cell carcinomas (BCCs).
Each treatment session involves gentle debridement or removal of scales for AK, Bowen's disease and superficial BCC, or debulking of nodular BCC, typically without the requirement for local anaesthesia.
In conventional PDT, the photosensitising cream is then applied 1mm thick to the treatment field for AK or the lesion (plus a 5mm margin), then covered with an occlusive dressing. This preparation takes approximately 15 minutes. The cream is left in place for 3 hours, the area is then wiped clean with saline and illumination is applied for 7–9 minutes.
More recently 'daylight PDT' with the photosensitiser methyl aminolevulinate (MAL; Lumexia) was approved by the Australian Therapeutic Goods Administration (TGA) for the treatment of AK. It is used as per the current product information with daylight exposure beginning within 30 minutes of the application of the photosensitiser MAL and continuing for 2 hours.
The alternative photosensitiser, 5-aminolevulinic acid (ALA), has also been investigated in PDT (ALA-PDT).
Good cosmetic results have been reported for PDT, with minimal scarring seen after most PDT treatments.
For AK, the recommended regimen is a single session of PDT, with the effects assessed at 3 months. Any residual lesions can, if required, then receive a second session of treatment.
For Bowen's disease and BCC, the recommended regimen is two sessions of treatment, 1 week apart, although in practice the interval between the two sessions may be up to a month.
Photodynamic therapy can be delivered in a single treatment session over large surface areas, and is therefore suitable for the treatment of patients with multiple AK.
Specialised equipment and training is required for PDT (except for daylight MAL-PDT). It is therefore primarily restricted to specialist use or use within centres specialising in skin cancer management.
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Overview of evidence (non-systematic literature review)
There is now a large body of evidence to support the use of PDT for the treatment of AK, including four phase III randomised controlled trials (RCTs) evaluating MAL-PDT and two evaluating ALA-PDT.
Photodynamic therapy is generally well tolerated by patients. Pain at the time of the illumination can be problematic and may require interventions such as the temporary suspension of illumination and/or the injection of local anaesthetic.
The introduction of daylight MAL-PDT has enabled longer, lower intensity light delivery. This advance has largely addressed the pain issue without compromising efficacy permitting the successful field treatment for large areas of AKs, provided that supervised preparation and application protocol is followed.
Bowen’s diseasecSCC in situ (also known as intra-epidermal SCC)
The efficacy of PDT in Bowen’s diseasecSCC in situ (also known as intra-epidermal SCC) has been shown to be at least equal to that of cryotherapy and 5-fluorouracil, with fewer complications and superior cosmetic outcomes.
A 64-month recurrence rate of 17% has been reported in Bowen’s diseasecSCC in situ (also known as intra-epidermal SCC).
Cutaneous squamous cell carcinoma
While some studies have demonstrated efficacy for the use of PDT in superficial cSCC, there have been relatively high recurrence rates.Thus, PDT cannot be recommended for the treatment of cSCC.
Basal cell carcinomaLonger-term (5-year) follow-up data demonstrate efficacy and good cosmetic results for PDT in the treatment of superficial BCC or nodular BCC.
Superficial basal cell carcinoma
An RCT comparing PDT with cryotherapy in the treatment of superficial BCC outcomes reported no difference in 5-year recurrence rates between the two treatments (20% with cryotherapy versus 22% for MAL-PDT p=0.86). The investigators noted that the cosmetic result was excellent with MAL-PDT (60% versus 16% with cryotherapy p=0.00078). A recent meta-analysis concluded PDT is an effective treatment for low-risk BCC, with excellent cosmesis and safety.
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Nodular cell basal cell carcinoma
With topical PDT for nodular BCC, delivery of sufficient photosensitiser and light to the full depth of the lesion is critical to achieve cure. Therefore, with the use of PDT for nodular BCCs greater than 2mm in depth, the response may be optimised by debulking the tumour prior to treatment with a curette or shave excision. Re-treatments may well be necessary in these circumstances.
An RCT comparing PDT with surgical excision in the treatment of nodular BCC reported 5-year clearance rates of 76% (95% confidence interval [CI] 59–87%) and 96% (95% CI 84–99%), respectively. The investigators noted that PDT was associated with a more favourable cosmetic outcome than surgery. A single-centre study reported that there were significantly higher estimated recurrence rates for nodular BCCs compared with superficial BCCs.
Photodynamic therapy does not complicate future surgery if it is required.
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