Methyl Aminolevulinate Photodynamic Therapy Research Articles

Photodynamic Therapy for the Treatment of Basal Cell Carcinoma: A Comprehensive Review of Randomized Controlled Trials.

Basal cell carcinoma (BCC) is the most common skin cancer worldwide and has been reported to have a rising incidence in the last years. Multiple therapeutic modalities are approved for the treatment of BCC, making it difficult for physicians to choose the most suitable option for every patient. Photodynamic therapy (PDT) using either 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) as photosensitizing agents is an established treatment option for low-risk BCC. This review aims to summarize the available evidence from randomized clinical trials (RCTs) that utilize either ALA or MAL PDT and compare it with other treatment modalities. The main outcomes related to the effectiveness, adverse events, cosmetic outcomes and pain sensation, along with data from long-term follow-ups will be presented and discussed. Thorough literature searches were conducted through the electronic databases ClinicalTrials. gov and Pubmed/MEDLINE from inception up to 28 March 2023. Only studies in English were included. All relevant data were extracted accordingly from the eligible studies. Eight RCTs included superficial BCC (sBCC) alone, 7 included nodular BCC (nBCC), 2 included both sBCC and nBCC and 1 included BCC of unspecified subtype. Follow-up duration ranged from 3 months to 5 years. Both ALA-PDT and MAL-PDT demonstrated acceptable efficacy, adverse events, cosmetic outcomes and pain sensation while no major differences were observed between them. PDT was less effective than surgery but with better reported cosmetic outcomes. PDT is a safe and efficacious treatment option for sBCC and to a lesser extent nBCC.

Simultaneous Skin Rejuvenation in Patients Undergoing Medical Treatment for Actinic Keratosis and Non-Melanoma Skin Cancer: A Case Series Analysis

This original article presents the findings of a comprehensive case series, shedding light on the efficacy of diverse treatment modalities for managing precancerous and cancerous skin lesions and their remarkable rejuvenation effects on the skin. A particular focus is placed on the promising outcomes achieved through the application of a combination treatment involving 5-Fluorouracil (5-FU) and salicylic acid, which demonstrates enduring and noteworthy results. Furthermore, alternative therapeutic approaches, including 5-FU monotherapy, Methyl aminolevulinate–photodynamic therapy (MAL-PDT), and the combination of Imiquimod therapy with MAL-PDT, exhibit substantial potential for patients seeking non-surgical solutions. These treatments manifest as valuable tools in improving skin texture and mitigating the effects of photodamage. Nevertheless, the intricate interplay between the chosen treatment, the extent of photodamage, and individual patient characteristics, with a particular emphasis on age, necessitates long-term follow-up to gauge treatment outcomes and the likelihood of lesion recurrence. Notably, these treatments are associated with a significant degree of inflammation, igniting curiosity regarding enhanced skin cellular turnover and the potential for a more youthful skin appearance. Our findings accentuate the promise of topical fluorouracil (5-FU) and photodynamic therapy (PDT) in combating photoaging among patients with actinic keratoses. However, a need for further in-depth research is evident to unravel the nuanced relationships between these treatments, the severity of photodamage, and the influence of patient-specific factors. Such comprehensive investigations are instrumental in optimizing patient care and outcomes, offering a holistic approach to managing photodamage within the context of actinic keratoses. This work, when combined with existing literature, provides valuable insights and serves as a catalyst for future research to fully unlock the potential of these treatments, ultimately enhancing the quality of patient care.

Surgical excision versus topical 5% 5-fluorouracil and photodynamic therapy in treatment of Bowen's disease: A multicenter randomized controlled trial

Randomized controlled trials comparing the effectiveness of 5-fluorouracil cream, methylaminolevulinate photodynamic therapy (MAL-PDT) and surgical excision in patients with Bowen's disease are lacking. background METHODS: In this multicenter non-inferiority trial, patients with a histologically proven Bowen's disease of 4-40mm were randomly assigned to excision with 5mm margin, 5% 5-fluorouracil cream twice daily for four weeks, or two sessions of MAL-PDT with one week interval. The primary outcome was the proportion of patients with sustained clearance at 12 months after treatment. A non-inferiority margin of 22% was used. Between May 2019 and January 2021, 250 patients were randomized. The proportion of patients with sustained clearance was 97.4% (75/77) after excision, 85.7% (66/77) after 5-fluorouracil and 82.1% (64/78) after MAL-PDT. Absolute differences were -11.7% (95% CI -18.9 to -4.5; P=0.0049) for 5-fluorouracil versus excision and -15.4% (95% CI -23.1 to -7.6; P=0.00078) for MAL-PDT versus excision. Both non-invasive treatments significantly more often led to good or excellent cosmetic outcome. results CONCLUSIONS: Based on our predefined non-inferiority margin of 22%, 5-fluorourcail is non-inferior to excision and associated with better cosmetic outcome. For MAL-PDT non-inferiority to excision cannot be concluded. Therefore, 5-fluorouracil should be preferred over excision and MAL-PDT in treatment of Bowen's disease.

Non-Invasive Treatment of Basal Cell Carcinoma: Photodynamic Therapy Following Curettage.

To investigate the effectiveness, safety, patient satisfaction, and cosmetic outcome of Methyl Aminolevulinate-Photodynamic Therapy (MAL-PDT) following curettage in order to make recommendations for its use in dermatology practices. A retrospective chart review of patients who received MAL-PDT following curettage for the indication of basal cell carcinoma (BCC) between 2009 and 2016 at a single private clinic in Ontario, Canada. Two hundred and seventy-eight patients with 352 BCC lesions were included, consisting of 44.2% males (n=123) and 55.8% females (n=155) with a mean age of 57.24 years. The primary outcome measurement consisted of the cure rate. Secondary outcome measurements included side effects, patient satisfaction, and cosmetic outcome, as reported in the medical charts. The overall cure rate was 90.3% (n=318). After controlling for age, sex, and lesion type, nasal lesions were approximately 2.82 (95% CI: 1.24-6.40, P=0.01) times more likely to experience a recurrence. 18.3% of patients (n=51) reported side effects, the most common being burning (n=19). Of those who expressed satisfaction, 100% (n=25) reported being happy. Of lesions with cosmetic data, 90.3% displayed a good response (n=149). MAL-PDT following curettage is an effective and safe treatment option for BCC lesions with a good cosmetic outcome and suggested high patient satisfaction. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7133.

How does imiquimod cream compare with methyl-aminolevulinate photodynamic therapy (MAL-PDT) for adults with basal cell carcinoma (BCC)?

How does imiquimod cream compare with methyl-aminolevulinate photodynamic therapy (MAL-PDT) for adults with basal cell carcinoma (BCC)?

The Role and Effectiveness of Photodynamic Therapy on Patients With Actinic Keratosis: A Systematic Review and Meta-Analysis.

Actinic keratoses (AKs) are the most common neoplastic lesions and are recognized as a precursor to squamous cell skin cancer. Photodynamic therapy (PDT) is a therapeutic option for multiple AKs in line with field cancerization. The aim of this study was to assess the effectiveness of PDT on patients with AKs using a meta-analysis, in order to evaluate the possible superiority of one treatment over the others. For this purpose, the PubMed, MEDLINE, Scopus, OVID, Science Direct, British Journal of Dermatology, Research Gate, and Embase databases were searched in March 2022. The search terms used were 'photodynamic therapy' and 'actinic keratosis'. We utilized the random-effects meta-analysis model to compare methyl aminolevulinate PDT (MAL-PDT) and the combination of a nanoscale-lipid vesicle formulation with the prodrug 5-aminolevulinic acid (BF-200 ALA) on a complete response (CR) of the lesions. Our meta-analysis indicated that the comparison of BF-200 ALA versus MAL-PDT showed marginally higher CRs than MAL-PDT.

Risk of Invasive Cutaneous Squamous Cell Carcinoma After Different Treatments for Actinic Keratosis

Treatment of actinic keratosis (AK) aims to prevent cutaneous squamous cell carcinoma (cSCC). However, whether AK can progress into invasive cSCC is a matter of debate, and little is known about the effect of treatment on preventing cSCC. To evaluate the risk of invasive cSCC and factors that may contribute to increased risk in patients with multiple AKs. In this secondary analysis of a multicenter randomized clinical trial, 624 patients with a minimum of 5 AKs within an area of 25 to 100 cm2 on the head were recruited from the Department of Dermatology of 4 hospitals in the Netherlands. Long-term follow-up was performed from July 1, 2019, to December 31, 2020. Patients were randomized to treatment with 5% fluorouracil, 5% imiquimod cream, methylaminolevulinate photodynamic therapy, or 0.015% ingenol mebutate gel. The primary outcome was the proportion of patients with invasive cSCC in the target area during follow-up. Secondary outcomes were the associations between risk of invasive cSCC and a priori defined potential prognostic factors, including type of treatment, severity of AK (Olsen grade), history of nonmelanoma skin cancer, and additional treatment. Of the 624 patients (558 [89.4%] male; median age, 73 years [range, 48-94 years]) in the study, 26 were diagnosed with a histologically proven invasive cSCC in the target area during follow-up. The total 4-year risk of developing cSCC in a previously treated area of AK was 3.7% (95% CI, 2.4%-5.7%), varying from 2.2% (95% CI, 0.7%-6.6%) in patients treated with fluorouracil to 5.8% (95% CI, 2.9%-11.3%) in patients treated with imiquimod. In patients with severe AK (Olsen grade III), the risk was 20.9% (95% CI, 10.8%-38.1%), and the risk was especially high (33.5%; 95% CI, 18.2%-56.3%) in patients with severe AK who needed additional treatment. In this secondary analysis of a randomized clinical trial, risk of invasive cSCC was highest in patients with Olsen grade III AK and was substantially increased in patients who received additional treatment. These patients should be closely followed up after treatment. ClinicalTrials.gov Identifier: NCT02281682.

Successful treatment of cutaneous pseudolymphoma with topical methylaminolevulinate photodynamic therapy.

article: Successful treatment of cutaneous pseudolymphoma with topical methylaminolevulinate photodynamic therapy - Italian Journal of Dermatology and Venereology 2021 December;156(Suppl. 1 to No. 6):50-1 - Minerva Medica - Journals

Optimizing treatment of acne with photodynamic therapy (PDT) to achieve long-term remission and reduce side effects. A prospective randomized controlled trial.

Photodynamic therapy with methyl aminolevulinate (MAL-PDT) is an effective treatment of acne vulgaris, but is associated with side effects. We performed a prospective randomized split-face study aimed at optimizing MAL-PDT treatment. Patients (n=33) were randomized to two or four treatments of PDT with MAL on one cheek and placebo vehicle on the other cheek, 1-2weeks apart. A 1.5-h pre-treatment with the MAL cream was followed by illumination with red light (20J/cm2). Assessments were performed before treatment and 4, 10, and 20weeks after the last treatment. In comparison to baseline, the number of inflammatory lesions at 20weeks on cheeks treated with MAL-PDT showed a relative decrease of 74% in the group with two treatments and 85% in the group with four treatments. This new treatment regimen for both MAL-PDT and red-light-only PDT, with shortened pre-treatment and reduced light dose, could be an effective modality.

How Much Protoporphyrin IX Must Be Activated to Obtain Full Efficacy of Methyl Aminolevulinate Photodynamic Therapy? Implication for Treatment Modifications.

Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is a popular treatment for actinic keratoses (AK), and several PDT treatment modalities with similar cure rates are in use. The effect relies on the activation of protoporphyrin IX (PpIX) in premalignant cells. This study aimed to measure PpIX during each treatment modality to determine the minimal PpIX activation and shortest exposure time for optimal cure rate. In four different treatment modalities, we established the PpIX formation up to three hours after MAL application without illumination and measured the speed of PpIX photoactivation during 9 min of red light (37 J/cm2). The level of PpIX three hours after MAL application was set to 100 PpIX units. In comparison, 85 PpIX units were formed during daylight PDT, 57 PpIX units during pulse PDT, and 52 PpIX units without any curettage prior to MAL. The activation of 50 PpIX units should, therefore, be enough to obtain a full effect on AK. Further, red light illumination may be shortened from 9 min to 1–2 min. The results indicate that PDT can be performed successfully with half the illumination time used in daylight PDT today and with one fourth of the illumination time used in classical PDT.

Treatment of cutaneous basal cell carcinoma with combined laser extirpation and methyl aminolevulinic acid: five-year success rates.

Basal cell carcinoma is the most common cancer. Excisional surgery is associated with a high clearance rate, at the expense of significant functional and aesthetic morbidity, especially within the T-zone or for extensive lesions. We report five-year follow-up outcomes for carbon dioxide laser extirpation of cutaneous basal cell carcinoma, assisted by immediate methyl aminolevulinate photodynamic therapy and cost-benefit considerations. Retrospective cohort database analysis of adult patients with biopsy-proven primary cutaneous basal cell carcinoma, completing five years of follow-up. Direct per-lesion cost was compared with conventional wide local excision. Patients with morphoeic basal cell carcinoma were excluded. Treated lesions were up to 1% total body surface area and up to 3.8mm (1.38 ± 0.695cm, mean ± standard deviation) in biopsy-proven depth. At the five-year follow-up mark, 93.6% of treated areas remained free of recurrence. Nodular basal cell carcinoma was the most common subtype (41.5%). A mean tumour depth greater than 2 ± 0.872mm was significantly associated with recurrence (Mann-Whitney, p = 0.0487). For a service delivered through the NHS at 2015 prices, we report a 43% saving, equating to a saving of £235 per basal cell carcinoma or a national annualised saving of £70 million by 2025 for the NHS. Our results suggest that CO2-assisted photodynamic therapy is non-inferior to excision but may offer better functional and cosmetic preservation at a fraction of the direct like for like cost of operative surgery. Investigation of this method by randomised controlled methodology is warranted.

The Effect of Four Approaches to Treat Actinic Keratosis on the Health-Related QOL, as Assessed by the Skindex-29 and Actinic Keratosis QOL

To evaluate the impact of actinic keratosis (AK) and the effect of four AK treatments on the health-related QOL (HRQOL), the Skindex-29 and AK QOL (AKQOL) questionnaires were completed by 624 patients with AK participating in a randomized controlled trial comparing 5% fluorouracil cream (Efudix, Meda Pharma B.V., Amstelveen, the Netherlands), 5% imiquimod cream (Aldara, Meda Pharma B.V., Solna, Sweden), methyl aminolevulinate (Metvix, Galderma SA, Penn Pharmaceutical Services, Gwent, UK) photodynamic therapy (MAL-PDT), and 0.015% ingenol mebutate gel (Picato, LEO Pharma A/S, Bellerup, Denmark) (Jansen et al., 2019).

Methyl aminolevulinate photodynamic therapy after partial debulking in the treatment of superficial and nodular basal cell carcinoma: 3-years follow-up.

The increase in the number of basal cell carcinoma (BCC) lesions has prompted use of minimally invasive therapies, including Photodynamic therapy (PDT). . The objective of the present work was to analyze the efficacy of methyl aminolevulinate-mediated photodynamic therapy (MAL-PDT) in patients suffering from superficial or nodular BCCs. A total of 220 BCC lesions (76 superficial and 144 nodular), clinically diagnosed and confirmed by histopathology analysis, were treated in 174 patients (mean age 72.5). Debulking using curettage was performed before two or three MAL-PDT sessions (λ = 630 nm; 90 J/cm2; 23 min) at 4-week intervals. Analyses of clinical clearance and cosmetic outcome were carried out by direct examination, dermoscopy, photographs, as well as by fluorescence diagnosis using a Wood's lamp. Evaluations were carried out at the different PDT sessions and follow-ups over a 3-year period. MAL-PDT was safe and highly tolerated. After an average of 2.6 MAL-PDT sessions, the overall clearance rate at 3-year follow-up was 96.1 % (95 % confidence interval [CI] 100 %-92 %) for superficial BCCs and 95.2 % (95 % [CI] 99 %-92 %) for nodular BCCs after an average of 2.7 sessions. Minimal side effects such as crushing, erythema and edema were reported. All BCC lesions showed excellent or good cosmetic results. The protocol followed in the present study has shown that MAL-PDT is a safe and effective treatment for superficial and nodular types of BCC.

MAL-associated methyl nicotinate for topical PDT improvement

Photosensitization of all tissue in sufficient quantity to generate damage is one of the limiting factors for Photodynamic Therapy (PDT) efficiency. Methyl nicotinate (MN) is a thermogenic and vasodilating substance that facilitates the topical tissue penetration of some compounds. The topical MAL (methyl aminolevulinate) PDT is commonly used as a precursor of protoporphyrin IX (PpIX). This study investigates the safety of topical use in NM, as well as its ability to improve the efficiency of topical PDT. For this, we investigate the cytotoxicity of MN, as well as its actions in increasing cellular metabolism and vasodilation. Besides, its ability to optimize the formation of PpIX in the tissue when associated with MAL cream was investigated, besides assessing the severity of necrosis obtained by treatments. The cytotoxicity of MN was tested for concentrations of 0, 0.1, 0.25, 0.5, 0.75 and 1% in cell culture. For the concentration of 0.5%, the cellular metabolism was evaluated using confocal microscopy to calculate the redox rate. In the Chorioallantoic Membrane Model, vasodilation was evaluated for concentrations of 0.5 and 1% MN during 1 h of incubation. In the animal model, the healthy skin of Wistar rat was used to evaluate the production of PpIX in the tissue and the degree of necrosis obtained by Photodynamic therapy when using NM associated with methyl aminolevulinate. It was observed the non-cytotoxicity in vitro of MN in the concentration used (0.5%) and its ability to increase cellular metabolism. In a chorioallantoic model, the MN vasodilation power was demonstrated for different caliber of vessels. In vivo studies are showing that the incorporation of MN in the MAL cream increases the amount of PpIX produced in the tissue causing a higher effect on the epidermis after PDT. This improvement of the protocol may make the procedure more effective both in the destruction of tumor tissue and in the treatment of deeper cells decreasing possible recurrence, in addition to allowing improvements in the protocol, such as reducing the cream's incubation time.

Methylene blue vs methyl aminolevulinate photodynamic therapy in the treatment of mild-to-moderate toenail onychomycosis: Short- and medium-term effects.

Photodynamic therapy (PDT) has emerged as an interesting alternative option for onychomycosis treatment. The impact of a specific photosensitizer (PS) on the final result is an important factor to consider. We conducted a short- and medium-term controlled trial to compare the effectiveness of PDT in the treatment of mild-to-moderate onychomycosis when it is mediated by two different PSs. Twenty patients were randomized to receive nine sessions of PDT distributed over 16 weeks mediated either by methylene blue (MB/PDT group) or methyl aminolevulinate (MAL/PDT group). Onychomycosis severity index (OSI) and nail involvement were checked along the study. Complete cure, treatment success, and clinical improvement were tabulated at 16 and 40-week follow-ups. OSI scores decreased significantly along the study, from 12.1 ± 5.4 to 3.6 ± 3.2 (MB/PDT group) and from 14.8 ± 6.0 to 5.4 ± 4.4 (MAL/PDT group). At 16-week follow-up, only 20% of the patients in the MB/PDT group reached complete cure and none in the group of MAL/PDT. At 40-week follow-up, complete cure rates were 70% and 40% in the MB/PDT group and MAL/PDT group respectively. Both modalities showed good outcomes in treatment of moderate toenail onychomycosis. MB/PDT showed a faster action but with relapse rates slightly higher than MAL/PDT.

Italian expert consensus paper on the management of patients with actinic keratoses

Two round tables involving experts were organized in order to reach a consensus on the management of patients with actinic keratosis (AK). In the first, seven clinical questions were selected and analyzed by a systematic literature review, using a Population, Intervention, Control, and Outcomes framework; in the second, the experts discussed relevant evidences and a consensus statement for each question was developed. Consensus was reached among experts on how to best treat AK patients with respect to different clinical scenarios and special populations. Lesion-directed treatments are preferred in patients with few AKs. Patients with multiple AKs are challenging, with more than one treatment usually needed to achieve complete lesion clearance or a high lesion response rate, therapy should be personalized, based on previous treatments, patient, and lesion characteristics. Methyl aminolevulinate-PDT, DL (day light) PDT, and imiquimod cream were demonstrated to have the lowest percentage of new AKs after post treatment follow-up. For IMQ 5% and 3.75%, a higher intensity of skin reactions is associated with higher efficacy. Photodynamic therapy (PDT) is the most studied treatment for AKs on the arms. Regular sunscreen use helps preventing new AKs. Oral nicotinamide 500 mg twice daily, systemic retinoids and regular sunscreen use were demonstrated to reduce the number of new squamous cell carcinomas in patients with AKs. Limited evidence is available for the treatment of AKs in organ transplant recipients. There is no evidence in favor or against the use of any of the available treatments in patients suffering from hematological cancer.

Methylene blue vs methyl aminolevulinate photodynamic therapy in combination with oral terbinafine in the treatment of severe dermatophytic toenail onychomycosis: Short- and long-term effects.

Photodynamic therapy (PDT) kills target microorganisms via reactive oxygen species (ROS) production. PDT seems to be a good alternative treatment option for onychomycosis. To compare the efficacy of combined therapies based on oral terbinafine (TN) plus adjunctive PDT mediated by methylene blue (MB) (TN+MB/PDT) or methyl aminolevulinate (MAL) (TN+MAL/PDT) in the treatment of onychomycosis. Twenty patients affected by severe dermatophyte onychomycosis in the nails of the big toe (>60% disease involvement of target nail) received oral TN for 12weeks and concomitantly were randomly allocated to receive nine sessions, separated by 2-week intervals, of urea (40%) plus a PDT protocol mediated by MB (TN+MB/PDT: group I) or mediated by MAL (TN+MAL/PDT: group II). Clinical and mycological efficacy was evaluated at 16-, 40- and 52-week follow-up. Both protocols showed a significant decrease in Onychomycosis Severity Index (OSI) scores (P<.05), from 24.2±4.6 to 0.7±0.6 (group I)) and from 18.5±10.1 to 2.1±2.0 (group II). No side effects or complications were reported in any of the combinations used. Mycological cure rates were significantly higher during the last third of the evaluated period of time, reaching 100% and 90% in group I and group II, respectively, at the 52-week follow-up. In both modalities, complete cure was achieved in 70% of the patients at the 52-week follow-up. TN+MB/PDT and TN+MAL/PDT show similar outcomes in the treatment of toenails with severe onychomycosis. PDT is an effective method to accelerate the TN-mediated healing process.

Successful treatment of cutaneous pseudolymphoma with topical methylaminolevulinate photodynamic therapy

article: Successful treatment of cutaneous pseudolymphoma with topical methylaminolevulinate photodynamic therapy - Giornale Italiano di Dermatologia e Venereologia 2020 Feb 05 - Minerva Medica - Journals

Sequential Treatment of Superficial Basal Cell Carcinomas With Topical Methyl Aminolevulinate Photodynamic Therapy and Imiquimod 5% Cream: A Retrospective Study of Clinical and Cosmetic Outcomes.

Topical photodynamic therapy (PDT) and imiquimod 5% (IMQ) cream are established treatments for superficial basal cell carcinoma (sBCC). Both have high initial response rates and recurrence rates of up to 37%. Recent studies demonstrate that PDT and imiquimod may act on sBCCs via synergistic immunomodulatory pathways. To describe the sequential use of MAL-PDT and imiquimod 5% cream in the treatment of sBCCs and report treatment tolerability, cosmetic outcomes, and efficacy. This is a retrospective case series of patients presenting over a 2-year period with primary sBCC who underwent 2 cycles of topical MAL-PDT, followed by 6 weeks of imiquimod 5% cream. Outcome measures were resolution of the index lesion at 3 months, side effects, cosmetic outcome, and long-term recurrence (LTR). A total of 17 consecutive patients (n = 17) with a combined 21 sBCCs (n = 21) were included. The median length of follow-up was 72 months (range 24-95 months). Long-term recurrence occurred in 2/21 lesions (10%). Sequential use of PDT and imiquimod was well tolerated with good cosmetic outcomes. The 10% LTR rate is at the lower end of the range reported for single modality treatment; however, larger samples are required to evaluate efficacy differences.

Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy.

BackgroundMethyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality.ObjectiveThe aim of this study was to identify potential biomarkers of BCC response to MAL-PDT.Material and methodsClinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated.ResultsThe retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01).Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94–159.8)ConclusionOur finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapy.