Pain perception during photodynamic therapy: why is daylight PDT with methyl aminolevulinate almost pain-free? A review on the underlying mechanisms, clinical reflections and resulting opportunities.

Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is an established and efficacious method for the treatment of non-melanoma skin cancer. However, treatment of especially larger areas often leads to pain, stinging and burning sensation during illumination. The use of daylight (DL) during MAL incubation was investigated in clinical trials and compared to conventional illumination with red LEDs. All clinical trials on MAL DL-PDT show it to be considerably and statistically significantly less associated with pain than conventional PDT while being as efficacious. Fluence rate and light dose seem to be the strongest indicators for pain during PDT. The article summarizes the current knowledge base and shows that the model is able to explain why activation by DL produces less to no pain. Recent clinical trials performed in other latitudes than Northern Europe or Australia confirm that MAL DL PDT is applicable also in regions closer to the equator. MAL DL-PDT carries the potential of MAL self-application by the patient. In several clinical trials, MAL DL-PDT has been compared to topical preparations being administered by the patients themselves. The results show that MAL DL-PDT is superior or at least non-inferior to the tested topical preparations and that its tolerability is better.