Interventions for basal cell carcinoma of the skin: systematic review
http://www.100md.com
《英国医生杂志》
1 Centre for Evidence-Based Dermatology, Queen's Medical Centre, Nottingham NG7 2UH, 2 Department of Dermatology, Queen's Medical Centre
Correspondence to: F Bath-Hextall fiona.bath-hextall@nottingham.ac.uk
Abstract
Basal cell carcinoma (BCC) is a form of skin cancer and the most common cancer found in humans1-3; it has diverse clinical appearances and morphology. BCCs are usually slow growing tumours that rarely spread to distant parts of the body.4 Growth of BCC is usually localised to the area of origin; however, some BCCs can infiltrate tissues in a three dimensional fashion that may not be obvious on visual inspection.3 5 If left untreated, or inadequately treated, the BCC can cause extensive destruction of tissue, particularly on the face. The clinical course of BCC is unpredictable; it may remain small for years, or it may grow rapidly or proceed by successive spurts of extension of tumour and partial regression.6
The tumour may occur at any age, but the incidence of BCC increases markedly after the age of 40. The incidence in younger people is increasing, however, possibly as a result of increased exposure to the sun. Risk factors are fair skin, tendency to freckle,7 high degree of sun exposure,8-10 excessive use of sun beds, previous radiotherapy, phototherapy, male sex, and genetic predisposition.11
The first line treatment of BCC is often surgical excision. Many alternatives are available, including curettage, cryosurgery, laser treatment, surgical excision with predetermined margins of clinically normal tissue, excision under frozen section control, Moh's micrographic surgery, radiotherapy, topical treatment, intralesional treatment, photodynamic therapy, immunomodulators, and chemotherapy. Although many treatments are used for BCC, little research is available that accurately compares these different treatment modalities against each other and for different types of tumour. With an increase in incidence of skin cancer,12 a good evidence base is important to inform treatment decisions.
Methods
Poor evidence base for most common human cancer
Despite the enormous workload associated with the treatment of BCC, very little good quality research has been done on the efficacy of the treatment modalities used. Most studies have been done on low risk BCCs, the results of which are probably not applicable to tumours of the morphoeic type and those occurring in difficult areas such as the nasolabial fold or around the ears and eyes. Specific trials or subgroup analyses are needed for morphoeic tumours. Two trials randomised patients with multiple BCCs, whereas all other trials randomised patients with one BCC. Pooling of data was not possible in many cases, as the trials did not have similar designs, methods, or outcome measures. Operator differences should also be taken into consideration, especially for cryotherapy and photodynamic therapy.
As nearly two thirds of all recurrent tumours appear in the first three years after treatment, and 18% appear between five and 10 years after treatment, our primary outcome measure for the review was recurrence at three to five years, measured clinically. Only one trial had a sufficient duration of follow up, and this found that the failure rate was significantly lower with surgery than with radiotherapy.15 For the other trials recurrence rates are difficult to judge as two trials had a follow up period of two years,16 23 four trials had a follow up period of one year,21 15 17 18 and 12 trials had a follow up period of six months or less.19 20 22 24 25 27-30 33 In general, the quality of the trials was poor. In 13 of the 18 trials the method of randomisation was not described or was unclear. Only four of the trials clearly showed that concealment of allocation was adequate. Only 12 of the 18 trials used an intention to treat analysis, and seven of those involved the therapeutic option imiquimod. Blinding of outcome assessment was done or attempted for most of the trials.
What is already known on this topic
Basal cell carcinoma of the skin is the most common form of human cancer; many tumours recur years after apparent initial clearance, and most are locally destructive
Excisional surgery, curettage and cautery, radiotherapy, cryotherapy, and more recently photodynamic therapy and imiquimod are the main treatments used
What this study adds
Only one trial included adequate long term data on recurrences of basal cell carcinoma, showing that excisional surgery with frozen section control was more effective than radiotherapy
Radiotherapy is associated with significant long term cosmetic defects, and the evidence for curettage and cautery, cryotherapy, photodynamic therapy, and imiquimod is inconclusive
Simple long term studies that document site, size, and type of basal cell carcinoma are needed to compare these treatments against excisional surgery
Strengths and limitations of this review
Our search for all published randomised controlled trials was rigorous, with no language restriction. All studies were assessed for quality and only considered in the meta-analysis if they were sufficiently similar in terms of study participants, interventions, and outcomes. We have chosen a primary outcome that best informs clinical practice. As with all systematic reviews, we may have missed some published and unpublished reviews. Several randomised controlled trials of imiquimod and photodynamic therapy reported in abstract form are likely to be published soon. These will be included as an update in our Cochrane review.13 Caution should be used in generalising the results of this review to people with Gorlin syndrome and other genetic syndromes, as responsiveness to some treatment modalities such as radiotherapy may be very different.
We are aware of a large number of case series reports on the different treatment modalities for primary BCCs. These studies cannot be included in our review of randomised controlled trials. However, they have been reviewed elsewhere,40 and the authors found that recurrence rates could not be compared owing to lack of uniformity in methods of reporting and were unable to propose general guidelines for the treatment of BCC.
A table of trials identified is on bmj.com
Contributors: FB-H did the electronic searches. FB-H and JB were involved in writing the protocol. WP and HW gave advice on the protocol. FB-H and JB were involved in extraction and entry of data. WP and JB were involved in checking the data and the report. HW gave advice and edited the final versions of the review. FB-H was responsible for the overall management and writing of the review and is the guarantor.
Funding: None.
Competing interests: FB-H, JB, WP, and HW are all involved in running a five year randomised controlled trial comparing imiquimod against excisional surgery for the treatment of low risk superficial and nodular basal cell carcinoma, which is funded by Cancer Research UK.
Ethical approval: Not needed.
References
Telfer N, Colver G, Bowers P. Guidelines for the management of basal cell carcinoma. Br J Dermatol 1999;141: 415-23.
Preston D, Stern R. Nonmelanoma cancers of the skin. N Engl J Med 1992;327: 1649-62.
Miller S. Biology of basal cell carcinoma (part 1). J Am Acad Dermatol 1991;24: 1-13.
Lo J, Snow S, Reizner G. Metastatic basal cell carcinoma: report of twelve cases with a review of the literature. J Am Acad Dermatol 1991;24: 715-9.
Breuninger H, Dietz K. Prediction of subclinical tumor infiltration in basal cell carcinoma. J Dermatol Surg Oncol 1991;17: 574-8.
Franchimont C. Episodic progression and regression of basal cell carcinomas. Br J Dermatol 1982;106: 305-10.
Gilbody J, Aitken J, Green A. What causes basal cell carcinoma to be the commonest cancer? Aust J Public Health 1994;18: 218-21.
Zaynoun S, Ali L, Shaib J. The relationship of sun exposure and solar elastosis to basal cell carcinoma. J Am Acad Dermatol 1985;12: 522-5.
Pearl D, Scott E. The anatomical distribution of skin cancers. Int J Epidemiol 1986;15: 502-6.
Mackie R, Elwood J, Hawks J. Links between exposure to ultraviolet radiation and skin cancer: a report of the Royal College of Physicians. J R Coll Physicians Lond 1987;21: 91-6.
Schrieber M, Moon T, Fox S, Davidson J. The risk of developing subsequent nonmelanoma skin cancers. J Am Acad Dermatol 1990;23: 1114-8.
Goodwin R, Roberts D. Skin cancer registration in the United Kingdom. Br J Dermatol 2001;145(suppl 59): 17.
Bath F, Bong J, Perkins W, Williams H. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev 2003;(4): CD003412.
Clarke M, Oxman A. Optimal search strategy for RCTs. Cochrane Reviewers' Handbook 4.1 (updated June 2000). Oxford: Cochrane Collaboration, 2000 (appendix 5c).
Avril M, Auperin A, Margulis A, Gerbaulet A, Duvillard P, Benhamou E, et al. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer 1997;76: 100-6.
Hall V, Leppard B, McGill J, Kesseler M, White J, Goodwin P. Treatment of basal-cell carcinoma: comparison of radiotherapy and cryotherapy. Clin Radiol 1986;37: 33-4.
Thissen M, Nieman F, Ideler A, Berretty P, Neumann H. Cosmetic results of cryosurgery versus surgical excision for primary uncomplicated basal cell carcinomas of the head and neck. Dermatol Surg 2000;26: 759-64.
Wang I, Bendsoe N, Klinterberg C, Enejder A, Andersson-Engels S, Svanberg S, et al. Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial. Br J Dermatol 2001;144: 832-40.
Soler A, Angell-Petersen E, Warloe T, Tausjo J, Steen H, Moan J, et al. Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources. Photochem Photobiol 2000;71: 724-9.
Alpsoy E, Yilmaz E, Basaran E, Yazar S. Comparison of the effects of intralesional interferon alfa-2a, 2b and the combination of 2a and 2b in the treatment of basal cell carcinoma. J Dermatol 1996;23: 394-6.
Cornell R, Greenway H, Tucker S. Intralesional interferon therapy for basal cell carcinoma. J Am Acad Dermatol 1990;23: 694-700.
Edwards L, Tucker S, Perednia D, Smiles K, Taylor E, Tanner D, et al. The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas. Arch Dermatol 1990;126: 1029-32.
Rogozinski T, Jablonska S, Brzoska J, Michalska I, Wohr C, Gaus W. Intralesional treatment with recombinant interferon beta is an effective alternative for the treatment of basal cell carcinoma: double-blind, placebo-controlled study. Prezeglad Dermatologiczny 1997;84: 259-63.
Romagosa R, Saap L, Givens M, Salvarrey A, Lin He J, Hsia S, et al. A pilot study to evaluate the treatment of basal cell carcinoma with 5-flourouracil using phosphatidyl choline as a transepidermal carrier. Dermatol Surg 2000;26: 338-40.
Miller B, Shavin J, Cognetta A, Taylor J, Salasche S, Korey A, et al. Nonsurgical treatment of basal cell carcinomas with intralesional 5-flourouracil/epinephrine injectable gel. J Am Acad Dermatol 1997;36: 72-7.
Punjabi S, Cook I, Kersey P, Marks R, Finlay A, Sharpe G, et al. A double-blind, multicentre parallel group study of BEC-5 cream in basal cell carcinoma. Eur Acad Dermatol Venereol 2000;14(suppl 1): 47-60.
Beutner K, Geisse J, Helman D, Fox T, Ginkel A, Owens M. Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream. J Am Acad Dermatol 1999;41: 1002-7.
Marks R, Gebauer K, Shumack S, Amies M, Bryden J, Fox T, et al. Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicentre 6-week dose-response trial. J Am Acad Dermatol 2001;44: 807-13.
Geisse J, Rich P, Pandaya A, Gross K, Andres K, Ginkel A, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol 2002;47: 390-8.
Sterry W, Ruzicka T, Herrera E, Takwale A, Bichel J, Andres K, et al. Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion. Br J Dermatol 2002;147: 1227-36.
Enejder A, Klinterberg C, Wang I, Andersson-Engels S, Bendsoe N, Svanberg S, et al. Blood perfusion studies on basal cell carcinomas in conjunction with photodynamic therapy and cryotherapy employing laser-doppler perfusion imaging. Acta Derm Venereol 2000;80: 19-23.
Mallon E, Dawber R. Cryosurgery in the treatment of basal cell carcinoma. Dermatol Surg 1996;22: 854-8.
Shumack S, Robinson J, Kossard S, Golitz L, Greenway H, Schroeter A, et al. Efficacy of topical 5% imiquimod cream for the treatment of nodular basal cell carcinoma. Arch Dermatol 2002;138: 1165-71.
Rhodes L, De Rie M, Engtrom Y. Photodynamic therapy using topical methyl aminolevulinate versus surgery for nodular basal cell carcinoma: results of a multicentre randomised prospective trial. Arch Dermatol 2004;140: 17-23.
Foley P. A phase III randomized study comparing photodynamic therapy (PDT) using Metvix or placebo cream in nodular basal cell carcinoma (BCC). Aust J Dermatol 2003;44: A5.
Basset-Seguin N, Ibbotson S, Emtestam L. Photodynamic therapy using methyl aminolevulinate is as efficacious as cryotherapy in basal cell carcinoma, with better cosmetic results . British Association of Dermatologists 83rd Annual Meeting, Brighton, July 2003. Br J Dermatol 2003;149(suppl 64): 46.
Tope WD, Menter A, El-Azhary RA. Randomized prospective comparison of topical methylaminolevulinate photodynamic therapy versus placebo photodynamic therapy in nodular basal cell carcinoma . 9 th World Congress of Cancers of the Skin, Seville, Spain, May 2003.
Caro I, Geisse JK, Lindholm J, Golitz L, Stampone P, Owens M. Efficacy and safety of imiquimod 5% cream in the treatment of superficial basal cell carcinoma . 12 th Congress of the European Academy of Dermatology and Venereology, Barcelona, Spain, 15th-18th October 2003.
Petit J, Avril M, Margulis A, Chassagne D, Gerbaulet A, Duvillard P. Evaluation of cosmetic results of a randomised trial comparing surgery and radiotherapy in the treatment of basal cell carcinoma of the face. Plast Reconstr Surg 2000;105: 2544-51.
Thissen M, Neumann H, Schouten L. A systematic review of treatment modalities for primary basal cell carcinoma. Arch Dermatol 1999;135: 1177-83.(Fiona Bath-Hextall, senio)
Correspondence to: F Bath-Hextall fiona.bath-hextall@nottingham.ac.uk
Abstract
Basal cell carcinoma (BCC) is a form of skin cancer and the most common cancer found in humans1-3; it has diverse clinical appearances and morphology. BCCs are usually slow growing tumours that rarely spread to distant parts of the body.4 Growth of BCC is usually localised to the area of origin; however, some BCCs can infiltrate tissues in a three dimensional fashion that may not be obvious on visual inspection.3 5 If left untreated, or inadequately treated, the BCC can cause extensive destruction of tissue, particularly on the face. The clinical course of BCC is unpredictable; it may remain small for years, or it may grow rapidly or proceed by successive spurts of extension of tumour and partial regression.6
The tumour may occur at any age, but the incidence of BCC increases markedly after the age of 40. The incidence in younger people is increasing, however, possibly as a result of increased exposure to the sun. Risk factors are fair skin, tendency to freckle,7 high degree of sun exposure,8-10 excessive use of sun beds, previous radiotherapy, phototherapy, male sex, and genetic predisposition.11
The first line treatment of BCC is often surgical excision. Many alternatives are available, including curettage, cryosurgery, laser treatment, surgical excision with predetermined margins of clinically normal tissue, excision under frozen section control, Moh's micrographic surgery, radiotherapy, topical treatment, intralesional treatment, photodynamic therapy, immunomodulators, and chemotherapy. Although many treatments are used for BCC, little research is available that accurately compares these different treatment modalities against each other and for different types of tumour. With an increase in incidence of skin cancer,12 a good evidence base is important to inform treatment decisions.
Methods
Poor evidence base for most common human cancer
Despite the enormous workload associated with the treatment of BCC, very little good quality research has been done on the efficacy of the treatment modalities used. Most studies have been done on low risk BCCs, the results of which are probably not applicable to tumours of the morphoeic type and those occurring in difficult areas such as the nasolabial fold or around the ears and eyes. Specific trials or subgroup analyses are needed for morphoeic tumours. Two trials randomised patients with multiple BCCs, whereas all other trials randomised patients with one BCC. Pooling of data was not possible in many cases, as the trials did not have similar designs, methods, or outcome measures. Operator differences should also be taken into consideration, especially for cryotherapy and photodynamic therapy.
As nearly two thirds of all recurrent tumours appear in the first three years after treatment, and 18% appear between five and 10 years after treatment, our primary outcome measure for the review was recurrence at three to five years, measured clinically. Only one trial had a sufficient duration of follow up, and this found that the failure rate was significantly lower with surgery than with radiotherapy.15 For the other trials recurrence rates are difficult to judge as two trials had a follow up period of two years,16 23 four trials had a follow up period of one year,21 15 17 18 and 12 trials had a follow up period of six months or less.19 20 22 24 25 27-30 33 In general, the quality of the trials was poor. In 13 of the 18 trials the method of randomisation was not described or was unclear. Only four of the trials clearly showed that concealment of allocation was adequate. Only 12 of the 18 trials used an intention to treat analysis, and seven of those involved the therapeutic option imiquimod. Blinding of outcome assessment was done or attempted for most of the trials.
What is already known on this topic
Basal cell carcinoma of the skin is the most common form of human cancer; many tumours recur years after apparent initial clearance, and most are locally destructive
Excisional surgery, curettage and cautery, radiotherapy, cryotherapy, and more recently photodynamic therapy and imiquimod are the main treatments used
What this study adds
Only one trial included adequate long term data on recurrences of basal cell carcinoma, showing that excisional surgery with frozen section control was more effective than radiotherapy
Radiotherapy is associated with significant long term cosmetic defects, and the evidence for curettage and cautery, cryotherapy, photodynamic therapy, and imiquimod is inconclusive
Simple long term studies that document site, size, and type of basal cell carcinoma are needed to compare these treatments against excisional surgery
Strengths and limitations of this review
Our search for all published randomised controlled trials was rigorous, with no language restriction. All studies were assessed for quality and only considered in the meta-analysis if they were sufficiently similar in terms of study participants, interventions, and outcomes. We have chosen a primary outcome that best informs clinical practice. As with all systematic reviews, we may have missed some published and unpublished reviews. Several randomised controlled trials of imiquimod and photodynamic therapy reported in abstract form are likely to be published soon. These will be included as an update in our Cochrane review.13 Caution should be used in generalising the results of this review to people with Gorlin syndrome and other genetic syndromes, as responsiveness to some treatment modalities such as radiotherapy may be very different.
We are aware of a large number of case series reports on the different treatment modalities for primary BCCs. These studies cannot be included in our review of randomised controlled trials. However, they have been reviewed elsewhere,40 and the authors found that recurrence rates could not be compared owing to lack of uniformity in methods of reporting and were unable to propose general guidelines for the treatment of BCC.
A table of trials identified is on bmj.com
Contributors: FB-H did the electronic searches. FB-H and JB were involved in writing the protocol. WP and HW gave advice on the protocol. FB-H and JB were involved in extraction and entry of data. WP and JB were involved in checking the data and the report. HW gave advice and edited the final versions of the review. FB-H was responsible for the overall management and writing of the review and is the guarantor.
Funding: None.
Competing interests: FB-H, JB, WP, and HW are all involved in running a five year randomised controlled trial comparing imiquimod against excisional surgery for the treatment of low risk superficial and nodular basal cell carcinoma, which is funded by Cancer Research UK.
Ethical approval: Not needed.
References
Telfer N, Colver G, Bowers P. Guidelines for the management of basal cell carcinoma. Br J Dermatol 1999;141: 415-23.
Preston D, Stern R. Nonmelanoma cancers of the skin. N Engl J Med 1992;327: 1649-62.
Miller S. Biology of basal cell carcinoma (part 1). J Am Acad Dermatol 1991;24: 1-13.
Lo J, Snow S, Reizner G. Metastatic basal cell carcinoma: report of twelve cases with a review of the literature. J Am Acad Dermatol 1991;24: 715-9.
Breuninger H, Dietz K. Prediction of subclinical tumor infiltration in basal cell carcinoma. J Dermatol Surg Oncol 1991;17: 574-8.
Franchimont C. Episodic progression and regression of basal cell carcinomas. Br J Dermatol 1982;106: 305-10.
Gilbody J, Aitken J, Green A. What causes basal cell carcinoma to be the commonest cancer? Aust J Public Health 1994;18: 218-21.
Zaynoun S, Ali L, Shaib J. The relationship of sun exposure and solar elastosis to basal cell carcinoma. J Am Acad Dermatol 1985;12: 522-5.
Pearl D, Scott E. The anatomical distribution of skin cancers. Int J Epidemiol 1986;15: 502-6.
Mackie R, Elwood J, Hawks J. Links between exposure to ultraviolet radiation and skin cancer: a report of the Royal College of Physicians. J R Coll Physicians Lond 1987;21: 91-6.
Schrieber M, Moon T, Fox S, Davidson J. The risk of developing subsequent nonmelanoma skin cancers. J Am Acad Dermatol 1990;23: 1114-8.
Goodwin R, Roberts D. Skin cancer registration in the United Kingdom. Br J Dermatol 2001;145(suppl 59): 17.
Bath F, Bong J, Perkins W, Williams H. Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev 2003;(4): CD003412.
Clarke M, Oxman A. Optimal search strategy for RCTs. Cochrane Reviewers' Handbook 4.1 (updated June 2000). Oxford: Cochrane Collaboration, 2000 (appendix 5c).
Avril M, Auperin A, Margulis A, Gerbaulet A, Duvillard P, Benhamou E, et al. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer 1997;76: 100-6.
Hall V, Leppard B, McGill J, Kesseler M, White J, Goodwin P. Treatment of basal-cell carcinoma: comparison of radiotherapy and cryotherapy. Clin Radiol 1986;37: 33-4.
Thissen M, Nieman F, Ideler A, Berretty P, Neumann H. Cosmetic results of cryosurgery versus surgical excision for primary uncomplicated basal cell carcinomas of the head and neck. Dermatol Surg 2000;26: 759-64.
Wang I, Bendsoe N, Klinterberg C, Enejder A, Andersson-Engels S, Svanberg S, et al. Photodynamic therapy vs. cryosurgery of basal cell carcinomas: results of a phase III clinical trial. Br J Dermatol 2001;144: 832-40.
Soler A, Angell-Petersen E, Warloe T, Tausjo J, Steen H, Moan J, et al. Photodynamic therapy of superficial basal cell carcinoma with 5-aminolevulinic acid with dimethylsulfoxide and ethylendiaminetetraacetic acid: a comparison of two light sources. Photochem Photobiol 2000;71: 724-9.
Alpsoy E, Yilmaz E, Basaran E, Yazar S. Comparison of the effects of intralesional interferon alfa-2a, 2b and the combination of 2a and 2b in the treatment of basal cell carcinoma. J Dermatol 1996;23: 394-6.
Cornell R, Greenway H, Tucker S. Intralesional interferon therapy for basal cell carcinoma. J Am Acad Dermatol 1990;23: 694-700.
Edwards L, Tucker S, Perednia D, Smiles K, Taylor E, Tanner D, et al. The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas. Arch Dermatol 1990;126: 1029-32.
Rogozinski T, Jablonska S, Brzoska J, Michalska I, Wohr C, Gaus W. Intralesional treatment with recombinant interferon beta is an effective alternative for the treatment of basal cell carcinoma: double-blind, placebo-controlled study. Prezeglad Dermatologiczny 1997;84: 259-63.
Romagosa R, Saap L, Givens M, Salvarrey A, Lin He J, Hsia S, et al. A pilot study to evaluate the treatment of basal cell carcinoma with 5-flourouracil using phosphatidyl choline as a transepidermal carrier. Dermatol Surg 2000;26: 338-40.
Miller B, Shavin J, Cognetta A, Taylor J, Salasche S, Korey A, et al. Nonsurgical treatment of basal cell carcinomas with intralesional 5-flourouracil/epinephrine injectable gel. J Am Acad Dermatol 1997;36: 72-7.
Punjabi S, Cook I, Kersey P, Marks R, Finlay A, Sharpe G, et al. A double-blind, multicentre parallel group study of BEC-5 cream in basal cell carcinoma. Eur Acad Dermatol Venereol 2000;14(suppl 1): 47-60.
Beutner K, Geisse J, Helman D, Fox T, Ginkel A, Owens M. Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream. J Am Acad Dermatol 1999;41: 1002-7.
Marks R, Gebauer K, Shumack S, Amies M, Bryden J, Fox T, et al. Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicentre 6-week dose-response trial. J Am Acad Dermatol 2001;44: 807-13.
Geisse J, Rich P, Pandaya A, Gross K, Andres K, Ginkel A, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled study. J Am Acad Dermatol 2002;47: 390-8.
Sterry W, Ruzicka T, Herrera E, Takwale A, Bichel J, Andres K, et al. Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion. Br J Dermatol 2002;147: 1227-36.
Enejder A, Klinterberg C, Wang I, Andersson-Engels S, Bendsoe N, Svanberg S, et al. Blood perfusion studies on basal cell carcinomas in conjunction with photodynamic therapy and cryotherapy employing laser-doppler perfusion imaging. Acta Derm Venereol 2000;80: 19-23.
Mallon E, Dawber R. Cryosurgery in the treatment of basal cell carcinoma. Dermatol Surg 1996;22: 854-8.
Shumack S, Robinson J, Kossard S, Golitz L, Greenway H, Schroeter A, et al. Efficacy of topical 5% imiquimod cream for the treatment of nodular basal cell carcinoma. Arch Dermatol 2002;138: 1165-71.
Rhodes L, De Rie M, Engtrom Y. Photodynamic therapy using topical methyl aminolevulinate versus surgery for nodular basal cell carcinoma: results of a multicentre randomised prospective trial. Arch Dermatol 2004;140: 17-23.
Foley P. A phase III randomized study comparing photodynamic therapy (PDT) using Metvix or placebo cream in nodular basal cell carcinoma (BCC). Aust J Dermatol 2003;44: A5.
Basset-Seguin N, Ibbotson S, Emtestam L. Photodynamic therapy using methyl aminolevulinate is as efficacious as cryotherapy in basal cell carcinoma, with better cosmetic results . British Association of Dermatologists 83rd Annual Meeting, Brighton, July 2003. Br J Dermatol 2003;149(suppl 64): 46.
Tope WD, Menter A, El-Azhary RA. Randomized prospective comparison of topical methylaminolevulinate photodynamic therapy versus placebo photodynamic therapy in nodular basal cell carcinoma . 9 th World Congress of Cancers of the Skin, Seville, Spain, May 2003.
Caro I, Geisse JK, Lindholm J, Golitz L, Stampone P, Owens M. Efficacy and safety of imiquimod 5% cream in the treatment of superficial basal cell carcinoma . 12 th Congress of the European Academy of Dermatology and Venereology, Barcelona, Spain, 15th-18th October 2003.
Petit J, Avril M, Margulis A, Chassagne D, Gerbaulet A, Duvillard P. Evaluation of cosmetic results of a randomised trial comparing surgery and radiotherapy in the treatment of basal cell carcinoma of the face. Plast Reconstr Surg 2000;105: 2544-51.
Thissen M, Neumann H, Schouten L. A systematic review of treatment modalities for primary basal cell carcinoma. Arch Dermatol 1999;135: 1177-83.(Fiona Bath-Hextall, senio)