Factors influencing pain and efficacy of topical photodynamic therapy: a retrospective study

This is the authors' abstract. We don't add key points for this paper.

Dear Editor, Photodynamic therapy (PDT) is widely used in dermatology, although it may be painful.1 2 Retrospective studies indicate that large treatment areas, head–neck sites, actinic keratosis (AK) and strong photosensitizer fluorescence may be predictive of PDT‐induced pain, but data are inconclusive.3 4 It is important to identify predictors of PDT‐induced pain to inform patients and practitioners. We investigated factors that may be associated with PDT‐induced pain and efficacy, in patients with superficial basal cell carcinoma (sBCC) and Bowen disease (BD). The study was undertaken in the Scottish PDT Centre, with Caldicott Guardian approval. Data relating to patient, lesion and treatment parameters and outcomes were retrieved from the in‐house PDT database and case notes. Patients included were those who commenced topical methyl aminolaevulinate (MAL) PDT between 1 January 2011 and 31 December 2013 for sBCC and/or BD. A 3‐h MAL application was followed by red light‐emitting diode irradiation (85 mW cm−2, 75 J cm−2; Aktilite; Galderma, Lausanne, Switzerland). Treatment was repeated at 1 week (first cycle) and clinical assessment was undertaken at 3 months, with a repeat treatment cycle performed if not clear, with follow‐up to 1 year. End points were assessed as in routine practice. Pain was assessed using a visual analogue scale (0–10 cm) immediately after PDT. Fluorescence using Wood's lamp (0–3 respectively for none, weak, moderate, strong) and erythema (0–3 for none, mild, moderate, severe) were graded visually, and clinical outcome (no response, partial or complete clearance) was assessed at > 10 months after treatment completion (1‐year outcome). Data from the first treatment for pain, fluorescence and erythema were used and assessed by linear regression models for the continuous outcome of pain, and logistic regression for the binary outcome of clear or not clear at 1 year. In these models, ‘clustering’ by patient was accounted for, recognizing that lesions within an individual are not independent. Exploratory multivariate analyses were conducted: the final models for pain included factors significant at P < 0·1 on univariate analyses. Assumptions for the models were checked, and Stata was used (StataCorp, College Station, TX, U.S.A.). Data for 173 lesions in 74 patients were included. The median age was 75 years (range 40–100), and 63% of lesions were in women. Of the lesions, 46% were sBCC, with a median diameter of 1·4 cm (range 0·3–10) and 95% 1‐year clearance. The remaining 54% were BD (median diameter 1·3 cm, range 0·2–10), with 93% 1‐year clearance. Most lesions in women were on the lower limbs, with 61% more (95% confidence interval 50–72%) in women than in men. The overall median pain score was 4·6. Women recorded higher pain scores than men (P = 0·009; Fig. 1a). Although highly significant, the difference in pain by sex was moderate, with women reporting a median of 1 cm (95% confidence interval 0·2–1·9) more pain than men (P = 0·021) on univariate analysis. Multivariate data analysis showing. (a) Pain scores on VAS scale against gender (64 lesions in 23 men, 109 lesions in 51 women), showing significantly higher pain scores for women than men (95% confidence interval for median difference 1·9 to 0·2; P = 0·02). (b) Pain scores on VAS scale against degree of fluorescence (0 = none; 1 = weak; 2 = moderate; 3 = strong) based on visual assessment and grading using a Wood's lamp examination (Equation for linear regression line: Pain = (0·68 × fluorescence) + 2·36; R2 = 0.036; p < 0·0001). (c) Pain on VAS against degree of erythema (0 = none; 1 = mild; 2 = moderate; 3 = strong) based on visual semi‐quantitative assessment (Equation for linear regression line: Pain = (0·76 × erythema) + 3·34; R2 = 0·033; P = 0·017). (d) Size of lesion (cm) against clinical outcome (clear or not clear) at one year (>10 months) after last PDT treatment, based on visual clinical assessment (P = 0·002). Pain increased as fluorescence increased (P < 0·001; Fig. 1b). However, fluorescence was not a good predictor, explaining only 3·6% of pain (R2 = 0·036). Pain also increased as erythema increased (P = 0·017; Fig. 1c). Although it was significantly associated with pain, erythema accounted for only 3·3% of pain (R2 = 0·033). Age, skin phototype, diagnosis, lesion site and size were not significantly associated with reported PDT‐induced pain. Most lesions cleared with PDT. However, smaller lesions were more likely to clear (P = 0·002; Fig. 1d). No association was found between any of the other variables examined and 1‐year clearance. Thus, female sex, strong fluorescence and erythema were associated with higher levels of reported PDT‐induced pain. However, these did not explain most of the pain experienced, highlighting the heterogeneous nature of PDT‐induced pain, the diversity of factors involved and the subjectivity of pain reporting. High clearance rates were achieved, particularly for smaller lesions. Study limitations include the retrospective design and that the data analysed were for first treatments. Assessments of fluorescence and erythema were semiquantitative rather than objective; which may have been more discriminating but are not undertaken routinely. As clearance rates were so high, it was difficult to analyse predictors of clearance. However, multivariate analysis, used to minimize confounding variables’ impact, helped to differentiate which variables were most associated with pain and outcome. This analysis differentiates this study from others, which used only univariate analyses.3 5 One report of PDT‐induced pain in 60 patients (69 lesions) reported pain to be higher in men, on the head, on larger treatment sites and with AK. However, there were confounding influences as it tends to be men with large areas of AK on the head and neck who are treated by PDT.3 Furthermore, a study of PDT‐induced pain in 121 patients showed higher pain scores at head–neck sites and for AK, but did not show an overall impact of sex.5 Thus, we have attempted to minimize the impact of confounding factors through the use of multivariate analysis and to provide information for PDT practitioners and patients regarding predictors of PDT‐induced pain and efficacy that may inform optimization of treatment. Funding sources: none. Conflicts of interest: S.H.I. has previously received honoraria and travel expenses from Galderma for presentations at meetings. E.L. received travel expenses from the Photobiology Unit in Dundee for her attendance at the European Society for Photodermatology Symposium at the European Academy of Dermatology and Venereology in Vienna.