10.2 Photodynamic therapy
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 disease, 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)[edit source]
Actinic keratosis[edit source]
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 disease[edit source]
A 64-month recurrence rate of 17% has been reported in Bowen’s disease.
Topical PDT is well suited for treatment of Bowen’s disease in slow healing sites such as the lower limb. Healing is quicker in these sites and there is less risk of the development of a non-healing ulcer or an infection compared with more destructive or surgical therapies.
Cutaneous squamous cell carcinoma[edit source]
While some studies have demonstrated efficacy for the use of PDT in superficial cSCC, there have been relatively high recurrence rates.
Basal cell carcinoma[edit source]
Superficial basal cell carcinoma[edit source]
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[edit source]
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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- Galderma Australia Pty Ltd. PI - Lumexia (methyl aminolevulinate). [homepage on the internet] Therapeutic Goods Administration; 2015 Available from: www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2015-PI-01846-1.
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- Leman JA, Mackie RM, Morton CA. Recurrence rates following aminolaevulinic acid-photodynamic therapy for intraepidermal squamous cell carcinoma compare favourably with outcome following conventional modalities. Br J Dermatol 2002;147(Suppl 62):35.
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- Basset-Seguin N, Ibbotson SH, Emtestam L, Tarstedt M, Morton C, Maroti M, et al. Topical methyl aminolaevulinate photodynamic therapy versus cryotherapy for superficial basal cell carcinoma: a 5 year randomized trial. Eur J Dermatol 2008 Sep;18(5):547-53 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18693158.
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- Foley P, Freeman M, Menter A, Siller G, El-Azhary RA, Gebauer K, et al. Photodynamic therapy with methyl aminolevulinate for primary nodular basal cell carcinoma: results of two randomized studies. Int J Dermatol 2009 Nov;48(11):1236-45 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20064185.
- Collier NJ, Haylett AK, Wong TH, Morton CA, Ibbotson SH, McKenna KE, et al. Conventional and combination topical photodynamic therapy for basal cell carcinoma: systematic review and meta-analysis. Br J Dermatol 2018 Dec;179(6):1277-1296 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29889302.
- Vinciullo C, Elliott T, Francis D, Gebauer K, Spelman L, Nguyen R, et al. Photodynamic therapy with topical methyl aminolaevulinate for 'difficult-to-treat' basal cell carcinoma. Br J Dermatol 2005 Apr;152(4):765-72 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15840111.
- Rhodes LE, de Rie M, Enström Y, Groves R, Morken T, Goulden V, et al. Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial. Arch Dermatol 2004 Jan;140(1):17-23 Available from: http://www.ncbi.nlm.nih.gov/pubmed/14732655.
- Tope WD, Menter A, El-Azhary.R.A., Lowe NJ, Jarratt MT, Pariser DM et al. Comparison of topical methyl aminolevulinate photodynamic therapy versus placebo photodynamic therapy in nodular BCC. J Eur Acad Dermatol Venereol 2004 [cited 2018 Oct 12];18(Suppl 2):413-414 Available from: https://doi.org/10.1016/j.jaad.2003.10.419.
- Lindberg-Larsen R, Sølvsten H, Kragballe K. Evaluation of recurrence after photodynamic therapy with topical methylaminolaevulinate for 157 basal cell carcinomas in 90 patients. Acta Derm Venereol 2012 Mar;92(2):144-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21918794.