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Photodynamic Therapy Followed by Mohs Micrographic Surgery Compared to Mohs Micrographic Surgery Alone for the Treatment of Basal Cell Carcinoma: Results of a Pilot Single-Blinded Randomised Controlled Trial

April 2015
Journal of Cutaneous and Aesthetic Surgery 8(2)

DOI:10.4103/0974-2077.158443

License
CC BY-NC-SA 4.0

Authors:

Firas Al-Niaimi

Aalborg University Hospital

Raj Mallipeddi

King's College London

Basal cell carcinoma is a common cutaneous malignant tumour. Surgical excision is the "gold standard" treatment for most subtypes, with Mohs micrographic surgery (MMS) offering the highest cure rate. Other treatment modalities used include photodynamic therapy (PDT). We aimed to study the efficacy of combining MMS with PDT to see whether this would reduce the number of stages and final defect size when compared with MMS alone. Our study was a single-centre, single-blinded, randomised and controlled pilot study involving a total of 19 patients. Nine patients were randomised to pre-treatment with PDT followed by MMS of whom two withdrew; the remaining 10 patients were randomised to the MMS alone. Follow-up visits were arranged at 3 and 6 months post-surgery. In the PDT arm, five out of the seven treated patients (71%) had their initial tumour size decreased following PDT treatment prior to MMS. The average number of stages in the PDT arm was 1.85, compared to 2.5 in the MMS arm. The average number of sections in the PDT arm was 4.2, in comparison to 5.2 in the MMS arm. Our pilot study showed a promising but limited role for PDT as an adjunct in MMS in the treatment of selected cases of basal cell carcinomas. Larger trials, preferably multi-centred are required to further examine the role of this combination therapy.

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Journal of Cutaneous and Aesthetic Surgery - Apr-Jun 2015, Volume 8, Issue 2

INTRODUCTION

Basal cell carcinoma (BCC) is a common malignant tumour

affecting predominantly the head and neck regions in fair

skin types. Although it has a very low mortality rate, it

can cause signicant morbidity by local tissue destruction

and invasion which can lead to disgurement.[1] Treatment

modalities used include Mohs micrographic surgery

(MMS) and photodynamic therapy (PDT).[2] We performed

a trial of the use of PDT prior to MMS in patients with

conrmed BCCs. The main objective of the study was to

assess whether the combination of PDT followed by MMS

is superior to MMS alone in the treatment of BCC in terms of

reducing both the post-MMS defect and the mean number

of stages required to achieve tumour clearance.

Study protocol and method

This was a single-centre, single-blinded, randomised

and controlled pilot study. The study was approved by

the St Thomas’ Hospital research ethics committee and

abided by the Helsinki protocol with an international

randomised controlled trial number of ISRCTN03814856.

The main inclusion criteria were male or female subjects

older than 18 years of age with the diagnosis of BCC

(except for the morphoeic, inltrative and subtypes)

greater than 1 × 1 cm2 in size and requiring treatment

with MMS. The exclusion of the aggressive subtypes in

our study is based on the lack of published evidence

of PDT in their management. The exclusion criteria

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DOI:

10.4103/0974-2077.158443

Photodynamic Therapy Followed by Mohs Micrographic Surgery

Compared to Mohs Micrographic Surgery Alone for the Treatment

of Basal Cell Carcinoma: Results of a Pilot Single-Blinded Randomised

Controlled Trial

Firas Al-Niaimi, Nisith Sheth, Habib A Kurwa1, Raj Mallipeddi

Dermatologic Surgery and Laser Unit, St John’s Institute of Dermatology, St Thomas’ Hospital, London, UK, 1Division of Dermatology, Department

of Medicine, University of Calgary, Calgary, Alberta, Canada

Address for correspondence: Dr. Firas Al-Niaimi, Department of Dermatology, Salford Royal Foundation Trust, Manchester, UK. E-mail: firas55@hotmail.com

Introduction: Basal cell carcinoma is a common cutaneous malignant tumour. Surgical excision is the “gold

standard” treatment for most subtypes, with Mohs micrographic surgery (MMS) offering the highest cure rate.

Other treatment modalities used include photodynamic therapy (PDT). Background: We aimed to study the

efficacy of combining MMS with PDT to see whether this would reduce the number of stages and final defect size

when compared with MMS alone. Materials and Methods: Our study was a single-centre, single-blinded,

randomised and controlled pilot study involving a total of 19 patients. Nine patients were randomised to pre-

treatment with PDT followed by MMS of whom two withdrew; the remaining 10 patients were randomised to

the MMS alone. Follow-up visits were arranged at 3 and 6 months post-surgery. Results: In the PDT arm, five

out of the seven treated patients (71%) had their initial tumour size decreased following PDT treatment prior to

MMS. The average number of stages in the PDT arm was 1.85, compared to 2.5 in the MMS arm. The average

number of sections in the PDT arm was 4.2, in comparison to 5.2 in the MMS arm. Conclusion: Our pilot

study showed a promising but limited role for PDT as an adjunct in MMS in the treatment of selected cases of

basal cell carcinomas. Larger trials, preferably multi-centred are required to further examine the role of this

combination therapy.

KEYWORDS: Basal cell carcinoma, Mohs micrographic surgery, Photodynamic therapy

ABSTRACT

original articlE

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Al-Niaimi: Photodynamic therapy in conjunction with Mohs micrographic surgery

Journal of Cutaneous and Aesthetic Surgery - Apr-Jun 2015, Volume 8, Issue 2 89

included; a photosensitive skin disorder, hypersensitivity

to methyl 5-aminolevulinate, participation in another

investigational drug or research study within 30 days of

study enrolment, and females of child-bearing potential.

All procedures were provided by the National Health

service and as such no cost analysis was performed.

All patients who entered the trial had an initial screening

visit. Once informed consent for participation in the

study was obtained, patients were randomised to

either MMS alone or PDT followed by MMS. In the arm

involving MMS alone, the procedure was performed

within 3 months of the baseline screening visit. The

treating physicians were blinded to whether the patients

underwent prior therapy with PDT or not and patients

were instructed from the outset not to disclose any

previous PDT participation. Subsequently, all patients

were followed up a week afterwards as part of the

wound care with regular follow-ups in 3 and 6 months

following treatment to assess the cosmetics outcome of

the procedure, any functional compromise; and to assess

the appearance and symptoms of the resultant scar tissue.

In the arm involving PDT followed by MMS, two

sessions of PDT treatment were applied 1 week apart

within 2 months of the initial baseline screening visit

with MMS being performed within 2-10 weeks following

PDT treatment (allowing for the inammation to settle).

PDT involved preparing the site with topical acetone

and light abrasion with curettage before application

of topical methyl aminolaevulinate cream (160 mg/g;

Metvix®, Photocure, Oslo, Norway) under an occlusive

dressing (Tegaderm, 3M Health Care, St Paul, MN, USA)

for 3 hours. This was performed by a single healthcare

professional for all the involved patients who was not

involved in the MMS procedures in order to ensure

consistency and to eliminate any bias. After 3 hours,

the dressing was removed and the cream wiped off.

Each lesion was then illuminated with non-coherent red

light (Aktilite CL128, Photocure, Oslo, Norway; average

wavelength 631 nm, light dose 37 J/cm2, light intensity

70-100 mW/cm2). The follow-up schedule was similar to

the MMS arm with visits after 3 and 6 months to ensure

there were no adverse events and to assess patients’

satisfaction with the scar.

RESULTS

A total of 19 patients were recruited into the study.

There were nine men and 10 women. The age range

was 41-89 (mean age of 62). Table 1 summarises all the

ndings of the trial. The majority of the BCC subtypes

were nodular (n = 15, 79%). The anatomical site for all

tumours was facial (cheeks, nose, and forehead). A total

of nine patients were randomised to the PDT followed

by MMS arm. Two patients withdrew from the study;

giving rise to a total of seven patients who completed

treatment with PDT and MMS. The remaining 10 patients

were randomised to undergo MMS only, all of whom

completed the treatment. This makes a total of 17 patients

who completed the treatment (89%).

Four out of the seven treated patients (71%) treated by

PDT showed a reduction in tumour size and surface area

prior to MMS. MMS in this group required an average

number of 1.85 stages to achieve tumour clearance,

compared to 2.5 in those patients who underwent MMS

alone. The average number of sections in the group

treated with PDT before MMS was 4.2, in comparison

to 5.2 in those patients who underwent MMS alone.

In the PDT arm, the mean surface area pre- and post-

MMS was 204 and 586 mm2, respectively In the MMS

arm the mean surface area was 201 mm2 prior to MMS

Table 1: Summary of results of the trial

Patient Age Sex Subtype Baseline size (mm)/Area (mm2) PDT Stages Sections Post-MMS size (mm)/Area (mm2)

1 84 F Nodular 12×16 (192) Ye s 1 2 14×19 (266)

2 57 F Nodular 12×10 (120) No 5 10 20×25 (500)

3 52 F Nodular 14×19 (266) Ye s xx xx xx

4 60 M Nodular 11×16 (176) No 2 5 15×27 (405)

5 89 M Nodular 11×13 (143) No 2 4 17×25 (425)

6 47 M Nodular 10×22 (220) No 1 4 28×8 (224)

7 72 F Nodular 13×8 (104) Ye s 2 6 19×48 (912)

8 44 F Nodular 12×10 (120) Ye s 2 4 17×17 (289)

9 46 F Adenoid 10×10 (100) Ye s xx xx xx

10 74 F Nodular 11×15 (165) No 2 3 17×23 (391)

11 81 F Nodular 13×16 (208) No 3 4 20×32 (640)

12 61 F Nodular 12×20 (240) Ye s 2 4 18×33 (594)

13 64 M Nodular 17×27 (459) Ye s 2 7 39×40 (1560)

14 54 F Nodular 11×22 (242) No 2 3 25×35 (875)

15 51 M Nodular 10×11 (110) Ye s 2 4 12×15 (180)

16 41 M Nodular 12×14 (168) No 2 3 14×18 (252)

17 79 M Nodular 11×19 (209) Ye s 2 4 16×19 (304)

18 51 M Nodular 12×13 (156) No 4 11 36×46 (1656)

19 73 M Nodular 17×24 (408) No 2 5 22×34 (748)

xx: Patient withdrew from study

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Al-Niaimi: Photodynamic therapy in conjunction with Mohs micrographic surgery

Journal of Cutaneous and Aesthetic Surgery - Apr-Jun 2015, Volume 8, Issue 2

and 612 mm2 afterwards. All PDT-related inammation

has settled at the time of MMS and measurements were

taken immediately prior to PDT or MMS treatment and

immediately post-MMS prior to surgical reconstruction.

A total of two patients withdrew from the study (11%),

one due to unexpected adverse reaction to the topical

Metvix® cream in the PDT arm in the form of irritant

dermatitis; the other patient withdrew from the study by

own choice but no specic reason was given. All patients

were satised with the resultant scar from the procedure,

with no differences between the two arms. Thirteen

patients (68%) completed the required follow-up at

6 months, none of whom had any clinical recurrence(s)

observed as would be expected in this time frame. An

image of post-PDT tumour shrinkage is provided from

a patient prior to our trial in our centre [Figures 1 and 2].

DISCUSSION

Several clinical and histological subtypes of BCC exist;

which include superficial, nodular, infiltrative, and

morphoeic.[2] MMS was originally described in the 1930s

as a way of excising difcult tumours.[3] The advantages

of MMS include both accurate removal of the tumour and

maximal tissue preservation. The cost effectiveness of the

procedure has also been proven.[4] The overall 5-year cure

rate is around 99% for primary BCCs and around 95%

for recurrent BCCs and therefore MMS is considered the

treatment of choice for high-risk BCCs including certain

sites such as the ears, lips, nose and eyes, aggressive

histological subtypes such as morphoeic, micronodular

and inltrative, size greater than 2 cm, recurrent BCCs,

and BCCs with perineural invasion.[2]

Other treatment modalities for BCCs include surgical

excision with predetermined margins, curettage and

cautery, cryotherapy, radiotherapy, and PDT.[1,2]

Combination therapy with MMS and other treatment

modalities has been shown to be of added benet in terms

of tumour clearance and post operative defect size. In one

study, MMS was combined with the immunomodulator

agent imiquimod 5% cream (Aldara®).[5] Data from that

trial demonstrated that pre-treatment with imiquimod

cream reduced the tumour size in primary nodular BCC

as well as reduction in the surgical defect size.

Topical PDT is a pharmacological treatment modality

predominantly for supercial and to a lesser extent

nodular BCCs[1,6] although BCCs often have a mixed

histology. Following absorption of the applied topical

photosensitizer, destruction of targeted cells and

apoptosis occurs once activated by a specific light

source that works through the formation of endogenous

photoactive porphyrins. It is an established treatment

for actinic keratoses and supercial BCCs and its main

advantages are the excellent cosmesis with little or no

scarring.[6,7]

In a relatively recent published work, PDT was used to

delineate tumour margins prior to MMS for supercial

and nodular BCCs and the results demonstrated a

possible role for this.[8]

Topical PDT as an adjunct to MMS has been used in

a series of four cases published by Kuijpers et al.[9]

In their cases, PDT was used after MMS in the event

of residual supercial BCC on the sections rather

than continuing with MMS. This allowed for smaller

wound defects and therefore better cosmesis. A

follow-up for a period of up to 27 months showed no

recurrences. Another study showed Metvix® PDT to

be an effective therapeutic modality in BCCs difcult

to treat by conventional means.[10] This included

large lesions (greater or equal to 15 mm on the face

or extremities and greater or equal to 20 mm on the

Figure 1: Large mixed component supercial and nodular

basal cell carcinoma right on the cheek

Figure 2: (a) Tumour shrinkage after two sessions of

photodynamic therapy which was excised by MMS (b)

Resultant scar at 3 months

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Al-Niaimi: Photodynamic therapy in conjunction with Mohs micrographic surgery

Journal of Cutaneous and Aesthetic Surgery - Apr-Jun 2015, Volume 8, Issue 2 91

trunk), ones in the H-zone of the face, on the ear or in

any patient with a high risk of surgical complications

due to bleeding abnormalities. Overall, there was a

complete lesion response rate of 90% at 3 months,

84% at 12 months, and 78% at 24 months with 84% of

patients considering the cosmetic outcome as good or

excellent at 24 months. In one patient, PDT was used

as an adjunct to MMS for a lesion measuring more

than 30 mm on the temple. Following PDT, the lesion

reduced in size substantially allowing for MMS to be

much more limited in extent.

Our study was a pilot trial involving a relatively small

number of patients and this could be a limitation. The

number of patients precluded any reliable statistical

analysis. Our ndings did not support a conclusive

benet for PDT prior to MMS.

Our target recruitment of 20 patients was not met owing

to difculties in recruitment into the study. This may

reect the difculties faced in recruiting patients when

a single centre is involved. Another limiting factor

was the number of visits required in the case of being

recruited to the PDT arm as most patients preferred less

hospital treatment visits. The dropout rate during the

trial was relatively low (10%), though only one patient

(5%) discontinued due to adverse events. More than

two-thirds of the initially recruited patients completed

the study with the designated periods of scheduled

follow-ups (68%). Though not expected due to the overall

high cure rates with MMS, no recurrences of clinically

evident tumours were observed in any of the patients

in both arms.

CONCLUSIONS

In conclusion, our pilot study suggests that PDT

has a limited role as a pre-treatment prior to MMS

in selected cases, particularly for larger supercial

tumours. Larger trials, preferably multi-centred are

required to provide a more detailed examination

on the role of PDT as an adjunctive treatment to

MMS. To our knowledge, this is the rst randomised

trial to assess for the efcacy and outcome of MMS

combination therapy with PDT.

REFERENCES

1. Wong CS, Strange RC, Lear JT. Basal cell carcinoma. BMJ 2003;327:794-8.

2. Telfer NR, Colver GB, Morton CA; British Association of Dermatologists.

Guidelines for the management of basal cell carcinoma. Br J Dermatol

2008;159:35-48.

3. Mohs FE. Chemosurgery: A microscopically controlled method of cancer

excision. Arch Surg 1941;42:279-95.

4. Tierney EP, Hanke CW. Cost effectiveness of Mohs micrographic surger y:

Review of the literature. J Drugs Dermatol 2009;8:914-22.

5. van der Geer S, Martens J, van Roij J, Brand E, Ostertag JU,

Verhaegh ME, et al. Imiquimod 5% cream as pretreatment of Mohs

micrographic surgery for nodular basal cell carcinoma in the

face: A prospective randomized controlled study. Br J Dermatol

2012;167:110-5.

6. Morton CA, Szeimies RM, Sidoroff A, Braathen LR. European guidelines

for topical photodynamic therapy part 1: Treatment delivery and

current indications - actinic keratoses, Bowen’s disease, basal cell

carcinoma. J Eur Acad Dermatol Venereol 2013;27:536-44.

7. Soler AM, Warloe T, Berner A, Giercksky KE. A follow-up study of

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nodular basal cell carcinomas treated with methyl 5-aminolaevulinate-

based photodynamic therapy alone and with prior curettage. Br J

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8. Tierney E, Petersen J, Hanke CW. Photodynamic diagnosis of tumor

margins using methyl aminolevulinate before Mohs micrographic

surgery. J Am Acad Dermatol 2011;64:911-8.

9. Kuijpers DI, Smeets NW, Krekels GA, Thissen MR. Photodynamic therapy

as adjuvant treatment of extensive basal cell carcinoma treated with

Mohs micrographic surgery. Dermatol Surg 2004;30:794-8.

10. 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;152:765-72.

How to cite this article: Al-Niaimi F, Sheth N, Kurwa HA, Mallipeddi R.

Photodynamic therapy followed by Mohs micrographic surgery compared

to Mohs micrographic surgery alone for the treatment of basal cell

carcinoma: Results of a pilot single-blinded randomised controlled trial.

J Cutan Aesthet Surg 2015;8:88-91.

Source of Support: Nil. Conict of Interest: None declared.

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The majority of studies were at low or unclear risk of bias for most domains. Twenty‐two studies were industry‐funded: commercial sponsors conducted most of the studies assessing imiquimod, and just under half of the photodynamic therapy (PDT) studies. Overall, surgical interventions have the lowest recurrence rates. For high‐risk facial BCC (high‐risk histological subtype or located in the facial 'H‐zone' or both), there may be slightly fewer recurrences with Mohs micrographic surgery (MMS) compared to surgical excision (SE) at three years (1.9% versus 2.9%, respectively) (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.16 to 2.64; 1 study, 331 participants; low‐certainty evidence) and at five years (3.2% versus 5.2%, respectively) (RR 0.61, 95% CI 0.18 to 2.04; 1 study, 259 participants; low‐certainty evidence). However, the 95% CI also includes the possibility of increased risk of recurrence and no difference between treatments. There may be little to no difference regarding improvement of cosmetic outcomes between MMS and SE, judged by participants and observers 18 months post‐operatively (one study; low‐certainty evidence); however, no raw data were available for this outcome. When comparing imiquimod and SE for nBCC or sBCC at low‐risk sites, imiquimod probably results in more recurrences than SE at three years (16.4% versus 1.6%, respectively) (RR 10.30, 95% CI 3.22 to 32.94; 1 study, 401 participants; moderate‐certainty evidence) and five years (17.5% versus 2.3%, respectively) (RR 7.73, 95% CI 2.81 to 21.3; 1 study, 383 participants; moderate‐certainty evidence). There may be little to no difference in the number of participant‐rated good/excellent cosmetic outcomes (RR 1.00, 95% CI 0.94 to 1.06; 1 study, 326 participants; low‐certainty evidence). However, imiquimod may result in greater numbers of good/excellent cosmetic outcomes compared to SE when observer‐rated (60.6% versus 35.6%, respectively) (RR 1.70, 95% CI 1.35 to 2.15; 1 study, 344 participants; low‐certainty evidence). Both cosmetic outcomes were measured at three years. Based on one study of 347 participants with high‐ and low‐risk primary BCC of the face, radiotherapy may result in more recurrences compared to SE under frozen section margin control at three years (5.2% versus 0%, respectively) (RR 19.11, 95% CI 1.12 to 325.78; low‐certainty evidence) and at four years (6.4% versus 0.6%, respectively) (RR 11.06, 95% CI 1.44 to 84.77; low‐certainty evidence). Radiotherapy probably results in a smaller number of good participant‐ (RR 0.76, 95% CI 0.63 to 0.91; 50.3% versus 66.1%, respectively) or observer‐rated (RR 0.48, 95% CI 0.37 to 0.62; 28.9% versus 60.3%, respectively) good/excellent cosmetic outcomes compared to SE, when measured at four years, where dyspigmentation and telangiectasia can occur (both moderate‐certainty evidence). Methyl‐aminolevulinate (MAL)‐PDT may result in more recurrences compared to SE at three years (36.4% versus 0%, respectively) (RR 26.47, 95% CI 1.63 to 429.92; 1 study; 68 participants with low‐risk nBCC in the head and neck area; low‐certainty evidence). There were no useable data for measurement at five years. MAL‐PDT probably results in greater numbers of participant‐ (RR 1.18, 95% CI 1.09 to 1.27; 97.3% versus 82.5%) or observer‐rated (RR 1.87, 95% CI 1.54 to 2.26; 87.1% versus 46.6%) good/excellent cosmetic outcomes at one year compared to SE (2 studies, 309 participants with low‐risk nBCC and sBCC; moderate‐certainty evidence). Based on moderate‐certainty evidence (single low‐risk sBCC), imiquimod probably results in fewer recurrences at three years compared to MAL‐PDT (22.8% versus 51.6%, respectively) (RR 0.44, 95% CI 0.32 to 0.62; 277 participants) and five years (28.6% versus 68.6%, respectively) (RR 0.42, 95% CI 0.31 to 0.57; 228 participants). There is probably little to no difference in numbers of observer‐rated good/excellent cosmetic outcomes at one year (RR 0.98, 95% CI 0.84 to 1.16; 370 participants). Participant‐rated cosmetic outcomes were not measured for this comparison. AEs with surgical interventions include wound infections, graft necrosis and post‐operative bleeding. Local AEs such as itching, weeping, pain and redness occur frequently with non‐surgical interventions. Treatment‐related AEs resulting in study modification or withdrawal occurred with imiquimod and MAL‐PDT. Authors' conclusions Surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with MMS over SE for high‐risk facial primary BCC (low‐certainty evidence). Non‐surgical treatments, when used for low‐risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. Of the non‐surgical treatments, imiquimod has the best evidence to support its efficacy. Overall, evidence certainty was low to moderate. Priorities for future research include core outcome measures and studies with longer‐term follow‐up.

Antibody Based Targeted Interventions for the Diagnosis and Treatment of Skin Cancers

Article

Full-text available

Jul 2020

Background Cutaneous malignancies most commonly arise from skin epidermal cells. These cancers may rapidly progress from benign to a metastatic phase. Surgical resection represents the gold standard therapeutic treatment of non-metastatic skin cancer while chemo- and/or radiotherapy are often used against metastatic tumors. However, these therapeutic treatments are limited by the development of resistance and toxic side effects, resulting from passive accumulation of cytotoxic drugs within healthy cells. Objective This review aims to elucidate how the use of monoclonal antibodies (mAbs) targeting specific tumor associated antigens (TAAs) are paving the way to improved treatment. These mAbs are used as therapeutic or diagnostic carriers that can specifically deliver cytotoxic molecules, fluorophores or radiolabels to cancer cells that overexpress specific target antigens. Results mAbs raised against TAAs are widely in use for e.g. differential diagnosis, prognosis and therapy of skin cancers. Antibody drug conjugates (ADCs) particularly show remarkable potential. The safest ADCs reported to date use non-toxic photo-activatable photosensitizers (PS), allowing targeted photodynamic therapy (PDT) resulting in targeted delivery of PS into cancer cells and selective killing after light activation without harming the normal cell population. The use of near infrared emitting photosensitizers enables both diagnostic and therapeutic applications upon light activation at the specific wavelengths. Conclusion Antibody based approaches are presenting an array of opportunities to complement and improve current methods employed for skin cancer diagnosis and treatment.

Non‐Prescription Acne Vulgaris Treatments: Their Role in our Treatment Armementarium: An International Panel Discussion

Article

Full-text available

May 2020

Background Acne vulgaris (Acne), a common inflammatory skin disorder, has its peak incidence between 14 – 19 years of age, with girls, frequently developing acne earlier than boys. Over recent years persistent acne is becoming more prevalent in adult women. Objectives This review and panel discussion addresses challenges in acne management, particularly in adult women. The role which non‐prescription acne treatment can play is explored when used as monotherapy or as an adjunctive treatment for acne of all severity. Methods The best available evidence on non‐prescription acne treatment was coupled with the opinion of an international expert panel of dermatologists to adopt statements and recommendations discussed in this review. Results All severity of acne has a significant burden on patients. Addressing environmental factors that are important for the individual with acne may help to educate, prevent, effectively manage, and maintain acne, per the panel. They agreed that the adult female acne population has unique needs because of their aging skin and social environment. Non‐prescription acne treatment products may help to balance the efficacy and tolerability of prescription acne treatment. Currently, there are no specific guidelines for how to use non‐prescription acne treatment products in these patients. Conclusion The panel agreed that guidelines including non‐prescription acne treatment either as monotherapy for mild acne or in combination with prescription treatments for more severe acne would address a significant unmet need.

Basal cell carcinoma

Article

Full-text available

Nov 2003
Br Med J

The authors of this review aim to provide a comprehensive overview of basal cell carcinoma, concentrating in particular on incidence, risk factors, molecular genetics, clinical features, and treatment

Photodynamic therapy with topical methyl aminolevulinate for “difficult-to-treat” basal cell carcinoma

Article

Full-text available

May 2005

Basal cell carcinoma (BCC) may be difficult to treat by conventional means, particularly if the lesions are large or located in the mid-face (H-zone). Photodynamic therapy (PDT) using topical methyl aminolaevulinate (MAL) may be a good noninvasive option for these patients. To investigate the efficacy and safety of PDT using MAL for BCCs defined as 'difficult to treat', i.e. large lesions, in the H-zone, or in patients at high risk of surgical complications. This was a prospective, multicentre, noncomparative study. Patients were assessed 3, 12 and 24 months after the last PDT treatment. One hundred and two patients with 'difficult-to-treat' BCC were treated with MAL PDT, using 160 mg g(-1) cream and 75 J cm(-2) red light (570-670 nm), after lesion preparation and 3 h of cream exposure. Results Ninety-five patients with 148 lesions were included in the per protocol analysis. The histologically confirmed lesion complete response rate at 3 months was 89% (131 of 148). At 12 months, 10 lesions had reappeared, and therefore the cumulative treatment failure rate was 18% (27 of 148). At 24 months, an additional nine lesions had reappeared, resulting in a cumulative treatment failure rate of 24% (36 of 148). The estimated sustained lesion complete response rate (assessed using a time-to-event approach) was 90% at 3 months, 84% at 12 months and 78% at 24 months. Overall cosmetic outcome was judged as excellent or good in 79% and 84% of the patients at 12 and 24 months, respectively. Follow-up is continuing for up to 5 years. MAL PDT is an attractive option for 'difficult-to-treat' BCC. Because of the excellent cosmetic results, the treatment is particularly well suited for lesions that would otherwise require extensive surgical procedures.

European guidelines for topical photodynamic therapy part 1: Treatment delivery and current indications - Actinic keratoses, Bowen's disease, basal cell carcinoma

Article

Nov 2012
J EUR ACAD DERMATOL

Topical photodynamic therapy (PDT) is a widely used non-invasive treatment for certain non-melanoma skin cancers, permitting treatment of large and multiple lesions with excellent cosmesis. High efficacy is demonstrated for PDT using standardized protocols in non-hyperkeratotic actinic keratoses, Bowen's disease, superficial basal cell carcinomas (BCC) and in certain thin nodular BCC, with superiority of cosmetic outcome over conventional therapies. Recurrence rates following PDT are typically equivalent to existing therapies, although higher than surgery for nodular BCC. PDT is not recommended for invasive squamous cell carcinoma. Treatment is generally well tolerated, but tingling discomfort or pain is common during PDT. New studies identify patients most likely to experience discomfort and permit earlier adoption of pain-minimization strategies. Reduced discomfort has been observed with novel protocols including shorter photosensitizer application times and in daylight PDT for actinic keratoses.

Imiquimod 5% cream as pretreatment of Mohs micrographic surgery for nodular basal cell carcinoma in the face: A prospective randomized controlled study

Article

Mar 2012
BRIT J DERMATOL

Imiquimod 5% cream can reduce or clear superficial and small nodular basal cell carcinoma (BCC). It could be used as a pretreatment of Mohs micrographic surgery (MMS) to decrease defect size. To study if a pretreatment with imiquimod 5% cream decreases defect size after MMS. In addition, to study the effect on the number of Mohs stages and reconstruction time. Seventy patients aged >18 years with a primary nodular BCC in the face were included. The imiquimod group used imiquimod 5% cream for 4 weeks, before MMS. The control group was treated with MMS only. Tumour and defect sizes were measured. We noted the number of Mohs stages, reconstruction time and side-effects. The median percentage increase in area from tumour size at baseline to the post-MMS defect for the imiquimod group was significantly less compared with the control group, 50% vs. 147% (P < 0·001). A tendency towards fewer Mohs stages in the imiquimod group was observed and the reconstruction time was significantly shorter in this group (P = 0·01). Imiquimod 5% cream as pretreatment of MMS significantly reduced the tumour size in primary nodular BCC and reduced the surgical defect size. Further research is necessary to investigate cost-effectiveness.

Photodynamic diagnosis of tumor margins using methyl aminolevulinate before Mohs micrographic surgery

Article

May 2011

Photodynamic therapy is an efficacious treatment modality for actinic keratoses and for superficial basal cell carcinoma (BCC) and squamous cell carcinoma. Only two prior case reports in the literature have used fluorescent diagnosis, with aminolevulinic acid, to define tumor margins. Twenty patients with BCCs of the head, neck, and upper extremities were enrolled in this prospective trial. Methyl aminolevulinate (MAL) (Metvixia, Galderma Laboratories, LP, Fort Worth, TX) was applied overnight (mean of 13.3 hours) before fluorescence measurements of tumor size using a clinical Wood lamp examination. A total of 5 (25.0%) superficial and 15 (75.0%) nodular BCCs were included in this trial. The mean tumor sizes were 263.0 mm(2) (post-Mohs micrographic surgery [MMS] defect), 239.1 mm(2) (fluorescent examination of MAL under Wood lamp), and 65.8 mm(2) (clinical size). Using interclass correlation coefficients, a high degree of consistency and absolute agreement between post-MMS defect size and fluorescent examination size was identified (interclass correlation coefficient .962). This correlation was significantly higher than that between post-MMS defect size and clinical examination (.703) and that between fluorescent and clinical examination (.651). Although this study demonstrates the clinical feasibility of using MAL in conjunction with a Wood lamp examination to delineate tumor margins before MMS for superficial and nodular BCCs, future large-scale studies are needed. The use of topical MAL as a photosensitizer in conjunction with a Wood lamp examination is a simple and inexpensive investigation that can be used before MMS to delineate the margins of ill-defined tumors.

Chemosurgical Treatment of Cancer of the Ear: A Microscopically Controlled Method of Excision

Article

May 1947
SURGERY

F E MOHS

In the treatment of cancer of the lip a chemosurgical procedure offers certain important advantages. As previously described,1 the chemosurgical method was devised to provide a microscopically controlled means for the excision of various accessible forms of cancer. The method entails, first, chemical fixation of the suspected tissues in situ and, second, systematic excision and microscopic examination of the fixed tissues. This process of fixation, excision and microscopic examination is repeated until a microscopically cancer-free surface is reached. The main advantages conferred by the microscopic control are (1) unprecedented reliability and (2) conservatism.TECHNIC Preparatory to the first application of the fixative the skin surrounding the cancer of the lip is freshly shaved, all crusts and scales are removed from the surface of the tumor and a keratolytic, such as dichloroacetic acid or a saturated solution of trichloroacetic acid, is applied until the surface becomes white. Keratolysis is necessary

Cost effectiveness of Mohs Micrographic surgery: review of the literature

Article

Oct 2009

A number of treatment modalities are currently in existence for non-melanoma skin cancer, including microscopically controlled surgical excision (e.g., Mohs micrographic surgery [MMS]), traditional surgical excision, radiation therapy, electrodessication and curettage, cryosurgery, photodynamic therapy and topical chemotherapeutic agents. MMS has the significant advantage of the lower recurrence rates of all treatment modalities, where five-year cure rates for MMS for primary BCCs are 1% relative to surgical excision (10.1%), electrodessication and curettage (7.7%), radiation therapy (8.7%) and cryotherapy (7.5%). Previous studies have also indicated, across specialties, that dermatologists have the highest rates for complete removal of non melanoma skin cancer (NMSC) which are significantly greater than those for otolaryngologists (P>0.02) and plastic surgeons (P<0.0008). To evaluate and compare the results of recent studies comparing the cost effectiveness of MMS to other treatment modalities performed by dermatologists and other physicians performing treatment of NMSC (otolaryngologic (ENT) surgeons, plastic surgeons, general surgeons). MMS is equivalent in cost to excision with permanent sections, 12% less costly than office based excision with frozen sections and 27% less costly than excision with frozen sections in an ambulatory surgical center (ASC). The most significant difference between MMS and surgical excision was the facility fee of excision with frozen sections in an ASC, (differential of

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555). With surgical excision, 32-39% of cases require a second procedure for clear margins. Additionally, with subsequent procedures for surgical excision cases, there is likely a greater volume of tissue removed and ramifications on functional preservation and cosmesis, which are difficult to quantify. Analysis of the existing literature on MMS relative to surgical excision confirms the value of MMS in both obtaining the highest initial cure rates and lowest recurrence rates. This analysis confirms that MMS is a cost effective treatment, which is lower in cost than surgical excision, which often includes an ASC facility fee and a subsequent re-excision procedure. Cost effectiveness analysis demonstrating the outcomes based efficiency of MMS are critical in the current health care climate with heightened sensitivity to financial pressures and declining reimbursement rates which may challenge our ability to provide patients with the optimal treatment for NMSC.

A follow-up study of recurrence and cosmesis in completely responding superficial and nodular basal cell carcinomas treated with methyl 5-aminolaevulinate-based photodynamic therapy alone and with prior curettage

Article

Oct 2001

Methyl 5-aminolaevulinate (mALA) is an ester derivative of 5-aminolaevulinic acid (ALA) with increased lipophilicity compared with ALA. To assess long-term cure rate, cosmesis, recurrence rate and extent of fibrosis after mALA-based photodynamic therapy (PDT) of superficial and nodular basal cell carcinomas (BCCs) showing early complete response to treatment. Of 350 BCCs treated, 310 responded completely. These were in 59 patients who were followed for 2-4 years (mean 35 months) after mALA-PDT. Nodular tumours were curetted before PDT, and mALA 160 mg g(-1) was applied to all tumours for 24 h or 3 h before illumination from a broad-band halogen light source with light doses from 50 to 200 J cm(-2). Fibrosis was assessed histologically in 23 biopsies. The overall cure rate for 350 BCCs, including non-responders and recurrences was 79%. Of 310 lesions, 277 (89%) remained in complete response, and the cosmetic outcome was excellent or good in 272 of the completely responding lesions (98%). Histological examination showed dermal fibrosis in one of 23 biopsies. We conclude that mALA-based PDT with prior curettage of nodular lesions is a promising new method for the treatment of BCC.

Chemosurgery: A method for the microscopically controlled excision of cancer of the skin and lips

Article