Roger I Ceilley, James Q Del Rosso
Current modalities and new advances in the treatment of basal cell carcinoma.
Int J Dermatol. 2006 May;45(5):489-98. doi: 10.1111/j.1365-4632.2006.02673.x.
Abstract/Text
Basal cell carcinoma (BCC) is one of the most common cancers. Surgical extirpation is currently the standard of care for BCC, which is associated with several advantages and disadvantages. Procedures such as surgical excision used to treat superficial BCC (sBCC) and nodular BCC (nBCC) may have high 5-year recurrence rates if tumors are not completely excised. Curettage with electrodesiccation is a common method for treating primary BCC. However, multiple cycles are recommended and the procedure can have unsatisfactory cosmetic results (e.g. scarring and hypopigmentation). Mohs micrographic surgery has a low rate of disease recurrence but is a specialized procedure usually limited to specific indications (e.g. high-risk tumors). Cryosurgery and photodynamic therapy require multiple cycles and are associated with variable cosmetic outcomes and recurrence rates. As with any procedure, potential risks and patient quality-of-life issues need to be considered. In addition, substantial patient and healthcare provider inconvenience limit the practical utility of some modalities. Pharmacologic interventions provide another treatment option as adjunctive or monotherapy. Investigations of imiquimod, a novel immune response modifier, have indicated that this topical, noninvasive agent is safe and well tolerated and may be efficacious in the treatment of BCC. This review will highlight the role of standard treatment modalities and introduce new advances in the treatment of BCC.
S W Menzies, K Westerhoff, H Rabinovitz, A W Kopf, W H McCarthy, B Katz
Surface microscopy of pigmented basal cell carcinoma.
Arch Dermatol. 2000 Aug;136(8):1012-6.
Abstract/Text
OBJECTIVES: To describe the relevant morphologic features and to create a simple diagnostic method for pigmented basal cell carcinoma (BCC) using in vivo cutaneous surface microscopy (ie, dermoscopy, dermatoscopy, or oil epiluminescence microscopy).
DESIGN: Pigmented skin lesions were photographed in vivo using immersion oil (surface microscopy). All pigmented skin lesions were excised and reviewed for histological diagnosis. Photographs of 142 pigmented BCCs, 142 invasive melanomas, and 142 benign pigmented skin lesions were randomly divided into 2 equally sized training and test sets. Images from the training set were scored for 45 surface microscopy features. From this a model was derived and tested on the independent test set.
SETTING: All patients were recruited from the primary case and referral centers of the Sydney Melanoma Unit, Sydney, Australia, and the Skin and Cancer Unit, Skin and Cancer Associates, Plantation, Fla.
PATIENTS: A random sample (selected from a larger database) of patients whose lesions were excised.
MAIN OUTCOME MEASURES: Sensitivity and specificity of the model for diagnosis of pigmented BCCs.
RESULTS: The following model was created. For a pigmented BCC to be diagnosed it must not have the negative feature of a pigment network and must have 1 or more of the following 6 positive features: large gray-blue ovoid nests, multiple gray-blue globules, maple leaflike areas, spoke wheel areas, ulceration, and arborizing "treelike" telangiectasia. On an independent test set the model had a sensitivity of 97% for the diagnosis of pigmented BCCs and a specificity of 93% for the invasive melanoma set and 92% for the benign pigmented skin lesion set.
CONCLUSION: A robust surface microscopy method is described that allows the diagnosis of pigmented BCCs from invasive melanomas and benign pigmented skin lesions. Arch Dermatol. 2000;136:1012-1016
楊達, 鈴木正, 土田哲也, 池田重雄. 基底細胞癌におけるデルマトスコピー所見の検討. 日皮会誌 1998;108:1249-56.
S E Presser, J R Taylor
Clinical diagnostic accuracy of basal cell carcinoma.
J Am Acad Dermatol. 1987 May;16(5 Pt 1):988-90.
Abstract/Text
The clinical diagnostic accuracy and index of suspicion of basal cell carcinoma were calculated. The data were compiled from dermatology residents, full-time dermatology university faculty, and dermatologists in private practice.
B Cribier, Y Scrivener, E Grosshans
Tumors arising in nevus sebaceus: A study of 596 cases.
J Am Acad Dermatol. 2000 Feb;42(2 Pt 1):263-8. doi: 10.1016/S0190-9622(00)90136-1.
Abstract/Text
BACKGROUND: Prophylactic surgical excision of nevus sebaceus (NS) during childhood is often recommended because various neoplasms can occur on NS. The proportion of malignant tumors occurring on NS is highly variable among the published series, and there are controversies on the nature of these neoplasms because many of the previously described basal cell carcinomas could actually be trichoblastomas, which are benign follicular tumors.
OBJECTIVE: We retrospectively analyzed all cases of NS of our collection, excised during the period from 1932 through 1998, and recorded all associated epithelial and nonepithelial changes. We especially differentiated basal cell carcinomas from trichoblastomas by silhouette analysis and examination of the stroma. These findings were analyzed according to gender, age, and localization.
METHODS: Microscopic analysis of NS by two examiners was performed independently of clinical data.
RESULTS: A total of 596 cases were included from 290 females and 306 males, mean age 25.4 years (range, 1 month to 87 years); 232 were excised in children younger than 16 years. NSs were located on the scalp in 49.8% of cases. Basal cell carcinomas were found in 5 cases (0.8%, mean age 39.3 years) and benign tumors in 81 cases (13.6%, mean age 46.3 years). Syringocystadenoma papilliferum (n = 30, 15 males, 15 females) and trichoblastoma (n = 28, 7 males, 21 females) were the most frequent benign tumors. NS with associated tumors were located on the scalp in 79% of cases. Only 4 benign tumors (1.7%) and 2 warts were observed in patients younger than 16 years. Various types of epithelial hyperplasia were noted that could not be considered neoplasms, as well as epidermal and apocrine cysts.
CONCLUSION: The rate of malignant tumors arising on NS was very low and we did not observe such cases in children, who had associated benign tumors in only 1.7% of cases. Benign neoplasms were common and most of them occurred on the scalp; this was not a bias resulting from a longer duration before surgery. Trichoblastoma and not basal cell carcinoma was the most frequent follicular tumor associated with NS and showed a striking female predominance. Most trichoblastomas had previously been misdiagnosed but could actually be easily recognized by typical histologic features. Because most tumors occurred in adults older than 40 years, our study suggests that prophylactic surgery in young children is of uncertain benefit. Clinical follow-up is probably sufficient, and even those cases with clinical changes often proved to be benign tumors or warts.
S Kaddu, H Schaeppi, H Kerl, H P Soyer
Basaloid neoplasms in nevus sebaceus.
J Cutan Pathol. 2000 Aug;27(7):327-37.
Abstract/Text
BACKGROUND: Nevus sebaceus (NS) (organoider nevus) may frequently be associated with the development of a number of benign and malignant neoplasms among which basaloid neoplasms are the most common. Histopathologic criteria for diagnosis and classification of basaloid proliferations arising in NS are still debated. Most previous investigators have considered them to represent mainly basal cell carcinomas (BCCs). On the contrary, a number of recent authors have proposed that most basaloid neoplasms in NS exhibit predominantly morphologic features implying benignancy, thus representing trichoblastomas (TBs). In this study, we attempted to characterize better the histopathologic features of basaloid neoplasms in NS in a large series based on current morphologic criteria.
METHODS: Three-hundred and sixteen cases of NS seen over 19 years were consecutively sampled and reviewed for basaloid neoplasms. Twenty-four cases of basaloid neoplasms in NS were identified and categorized based on current histopathologic criteria either as TB or BCC. For comparison of histopathologic features, 37 solitary TB were also studied.
RESULTS: Following histopathologic analysis, 22 cases were categorized as TB (91.6%, 10 males, 12 females; mean age 40.8 years, range 19-78 years) and 2 cases as BCC (8.4%, 1 male, 1 female; 32 years and 40 years). Clinical features in both groups were generally similar. The lesions presented exclusively on the head and neck as skin colored to pigmented papules or nodules within NS (scalp in 19 TB cases and 1 BCC case; face in 2 TB cases and 1 BCC case; neck in 1 TB case). Histopathologically, TB in NS were characterized by smooth-bordered basaloid aggregations with either a nodular and/or a superficial pattern, abundant fibrous stroma with focal clefts within the stroma, and prominent features of limited follicular differentiation (rudimentary follicular germs in concert with papillae). In contrast, BCC in NS showed basaloid aggregations that vary markedly in size and shape, scant fibrous stroma, focal mucinous clefts between basaloid aggregations and surrounding stroma, and lack of prominent rudimentary follicular germs in concert with papillae. Remarkably, sections in a few cases of TB showed features occasionally found in BCCs but presently widely considered to be unspecific (e.g., ulceration, cystic degeneration, and focal clefts between basaloid aggregations and surrounding stroma). Two cases of TB in NS were associated with a sebaceoma and 1 case with a desmoplastic trichilemmoma. Follow-up data in 14 TB cases and 2 BCC cases (mean follow-up 28.8 months; range 1 to 160 months) revealed no local recurrences or distant metastases.
CONCLUSION: Our study confirms that the vast majority of the basaloid neoplasms arising in NS show clear-cut morphologic criteria for TB, whereas only a few cases display histopathologic features consistent with BCC. In a minority of cases, basaloid neoplasms with overall morphologic features of TB may present problems in diagnosis when they exhibit a few histopathologic features traditionally associated with BCC or when they occur in combination with other adnexal neoplasms.
M A Muñoz-Pérez, M J García-Hernandez, J J Ríos, F Camacho
Sebaceus naevi: a clinicopathologic study.
J Eur Acad Dermatol Venereol. 2002 Jul;16(4):319-24.
Abstract/Text
OBJECTIVE: To analyse sebaceus naevus (SN) incidence, associated malignancies, and developmental defects in a retrospective study.
METHODS: We retrospectively analysed all cases of SN excised in our Department over a 20-year period. All cases of epidermal naevus syndrome (Schimmelpenning syndrome) associated with SN were recorded, as well as all patients with histological changes suggesting degeneration of the initial SN.
RESULT: A total 226 patients with SN were included in the study. Stage II was the most common (65%), and the parietal area was the most common location of SN (42%), with only 7% located in non-scalp areas. Syringocystadenoma papilliferum and trichoblastoma were the most common tumours arising on SN. We only found five patients with basal cell carcinoma arising on previous SN. Epidermal naevus syndrome associated with SN was diagnosed in 16 patients, and this was the most common neurocutaneous association.
CONCLUSION: The incidence of malignancy arising on SN was very low, indicating that prophylactic surgery of NS in children is not recommendable. Developmental defects should be investigated in order to evidence possible epidermal naevus syndrome associated with SN.
M R Thissen, M H Neumann, L J Schouten
A systematic review of treatment modalities for primary basal cell carcinomas.
Arch Dermatol. 1999 Oct;135(10):1177-83.
Abstract/Text
OBJECTIVE: To systematically review the literature for studies reporting on recurrence rates of basal cell carcinomas (BCCs) after different therapies.
DESIGN: We reviewed all studies published in English, French, German, Dutch, Spanish, or Italian between 1970 and 1997 that prospectively examined recurrence rates for at least 50 patients with primary BCCs observed for at least 5 years after treatment with Mohs micrographic surgery, surgical excision, curettage and electrodesiccation, cryosurgery, radiotherapy, immunotherapy with interferon or fluorouracil, or photodynamic therapy.
SETTING: Department of Dermatology, University Hospital Maastricht, Maastricht, the reference center for dermatologic oncology and Mohs micrographic surgery in the Netherlands.
MAIN OUTCOME MEASURES: The recurrence rates after different therapies for BCCs, resulting in the development of guidelines for the treatment of these disorders.
RESULTS: Of 298 studies found in several electronic databases, only 18 met the requirements and could be used for analysis. Tumors treated with Mohs micrographic surgery show the lowest recurrence rates after 5 years, followed in order by those treated with surgical excision, cryosurgery, and curettage and electrodesiccation.
CONCLUSIONS: Recurrence rates for different therapies could not be compared because of a lack of uniformity in the method of reporting, so evidence-based guidelines could not be developed. We surmise that Mohs micrographic surgery should be used mainly for larger, morphea-type BCCs located in danger zones. For smaller BCCs of the nodular and superficial types, surgical excision remains the first treatment of choice. Other treatment modalities can be used in patients in whom surgery is contraindicated. Immunotherapy and photodynamic therapy are still investigative.
F J Bath-Hextall, W Perkins, J Bong, H C Williams
Interventions for basal cell carcinoma of the skin.
Cochrane Database Syst Rev. 2007 Jan 24;(1):CD003412. doi: 10.1002/14651858.CD003412.pub2. Epub 2007 Jan 24.
Abstract/Text
BACKGROUND: Basal cell carcinoma (BCC) is the commonest skin cancer. BCCs are slow-growing, locally invasive, epidermal skin tumours which mainly affect white skinned people. The first line treatment is usually surgical excision, but numerous alternatives are available.
OBJECTIVES: To assess the effects of treatments for basal cell carcinoma.
SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (January 2006), the Cochrane Central Register of Controlled Trials (The Cochrane LIbrary Issue 1, 2006), the Cochrane Database of Systematic Reviews (The Cochrane Library Issue 1, 2006), MEDLINE (2004 to January 2006), EMBASE (2005 to January 2006), the metaRegister of Controlled Trials (February 2006). Cited references of all trials identified and key review articles were searched. Pharmaceutical companies were contacted where appropriate for reviews or unpublished trials.
SELECTION CRITERIA: Inclusion criteria were adults with one or more histologically proven, primary basal cell carcinoma. The primary outcome measure was recurrence at three to five years, measured clinically. The secondary outcome included early treatment failure within six months, measured histologically. Adverse treatment effects included aesthetic appearance and pain during and after treatment.
DATA COLLECTION AND ANALYSIS: Two authors independantly carried out study selection and assessment of methodological quality.
MAIN RESULTS: Twenty seven studies were identified. Only one RCT of surgery versus radiotherapy had primary outcome data at four years, showing significantly more persistent tumours and recurrences in the radiotherapy group as compared to the surgery group, (RR 0.09, 95%CI, 0.01 to 0.69). One study found no significant difference for recurrence at 30 months when Moh's micrographic surgery was compared to surgery for high risk facial BCCs, (RR 0.64, 95%CI 0.16,2.64). One study of methylaminolevulinate photodynamic therapy (MAL PDT) versus cryotherapy found no significant difference in recurrences in the MAL PDT group when compared to cryotherapy at one year (RR 0.50, 95% CI 0.22,1.12). Cryotherapy showed no significant difference in recurrences at one year when compared to surgery on one small study. When radiotherapy was compared to cryotherapy there were significantly fewer recurrences at one year in the radiotherapy group compared to the cryotherapy group.Short-term studies suggest a success rate of 87 to 88% for imiquimod in the treatment of superficial BCC using a once-daily regimen for 6 weeks and a 76% treatment response when treating nodular BCC for 12 weeks, when measured histologically.
AUTHORS' CONCLUSIONS: Overall there has been very little good quality research on treatments for BCC. Most trials have only evaluated BCCs in low risk locations. Surgery and radiotherapy appear to be the most effective treatments with surgery showing the lowest failure rates. Although cosmetic outcomes appear good with PDT, long term follow up data are needed. Other treatments might have some use but few have been compared to surgery. An ongoing study comparing imiquimod to surgery should clarify whether imiquimod is a useful option.
M F Avril, A Auperin, A Margulis, A Gerbaulet, P Duvillard, E Benhamou, J C Guillaume, R Chalon, J Y Petit, H Sancho-Garnier, M Prade, J Bouzy, D Chassagne
Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study.
Br J Cancer. 1997;76(1):100-6.
Abstract/Text
Basal cell carcinomas (BCCs) are very frequent cutaneous cancers, often located on the face. Cure rates with surgery and radiotherapy are high, but these treatments have never been compared prospectively. A randomized trial was initiated in 1982 to compare surgery and radiotherapy in the treatment of primary BCC of the face measuring less than 4 cm. The primary end point was the failure rate (persistent or recurrent disease) after 4 years of follow-up. The secondary end point was the cosmetic results assessed by the patient, the dermatologist and three persons not involved in the trial. In the course of the trial, 347 patients were treated. Of the 174 patients in the surgery group, 71% had local anaesthesia and 91% frozen section examination. Of the 173 patients in the radiotherapy group, 55% were treated with interstitial brachytherapy, 33% with contactherapy and 12% with conventional radiotherapy. The 4-year actuarial failure rate (95% CI) was 0.7% (0.1-3.9%) in the surgery group compared with 7.5% (4.2-13.1%) in the radiotherapy group (log-rank P = 0.003). The cosmetic results assessed by four of the five judges were significantly better after surgery than after radiotherapy. Eighty-seven per cent of the surgery-treated patients and 69% of the radiation-treated patients considered the cosmetic result as good (P < 0.01). Thus, in the treatment of BCC of the face of less than 4 cm in diameter, surgery should be preferred to radiotherapy.
Nicole W J Smeets, Gertruud A M Krekels, Judith U Ostertag, Brigitte A B Essers, Carmen D Dirksen, Fred H M Nieman, H A Martino Neumann
Surgical excision vs Mohs' micrographic surgery for basal-cell carcinoma of the face: randomised controlled trial.
Lancet. 2004 Nov 13-19;364(9447):1766-72. doi: 10.1016/S0140-6736(04)17399-6.
Abstract/Text
BACKGROUND: Rates of recurrence of facial basal-cell carcinoma are consistently lower after Mohs' micrographic surgery (MMS) than after other treatments, such as surgical excision (SE). However, MMS is more time-consuming and therefore more expensive than SE. We investigated the types of facial basal-cell carcinomas in which MMS was more effective than SE.
METHODS: 408 primary and 204 recurrent facial carcinomas (374 and 191 patients, respectively) were analysed separately in this prospective randomised study. Patients were assigned SE or MMS (each 204 primary, 102 recurrent), and received treatment at two hospitals in the Netherlands. The primary outcome was recurrence of carcinoma. Analysis was by intention to treat.
FINDINGS: Of the basal-cell carcinomas included in the trial, 397 primary (198 MMS, 199 SE) and 201 recurrent (99, 102) tumours were actually treated. Of patients with primary carcinomas, 21 had both MMS and SE on different tumours. Nine with recurrent carcinomas had both treatments on different skin tumours. 66 primary and 13 recurrent carcinomas were lost to follow-up. Of the primary carcinomas, five (3%) recurred after SE compared with three (2%) after MMS during 30 months of follow-up. Of the recurrent carcinomas, three (3%) recurred after SE and none after MMS during 18 months of follow-up. Four recurrent carcinomas randomly assigned to the SE group were treated with MMS. Although both differences favoured MMS, they were not significant (primary, difference 1% [95% CI -2.5% to 3.7%], p=0.724; recurrent, 3.2% [-2.0% to 5.0%], p=0.119). Total operative costs of MMS were higher than those of SE (primary 405.79 Euros vs 216.86 Euros, recurrent 489.06 Euros vs 323.49 Euros; both p<0.001).
INTERPRETATION: No definitive conclusion on recurrence rates of primary or recurrent basal-cell carcinomas is yet possible. Although recurrence rates were lower after MMS than after SE, the differences were not significant.
Yusuf Gulleth, Nelson Goldberg, Ronald P Silverman, Brian R Gastman
What is the best surgical margin for a Basal cell carcinoma: a meta-analysis of the literature.
Plast Reconstr Surg. 2010 Oct;126(4):1222-31. doi: 10.1097/PRS.0b013e3181ea450d.
Abstract/Text
BACKGROUND: Current management of basal cell carcinoma is surgical excision. Most resections use predetermined surgical margins. The basis of ideal resection margins is almost completely from retrospective data and mainly from small case series. This article presents a systematic analysis from a large pool of data to provide a better basis of determining ideal surgical margin.
METHODS: A systematic analysis was performed on data from 89 articles from a larger group of 973 articles selected from the PubMed database. Relevant inclusion and exclusion criteria were applied to all articles reviewed and the data were entered into a database for statistical analysis.
RESULTS: The total number of lesions analyzed was 16,066; size ranged from 3 to 30 mm (mean, 11.7 ± 5.9 mm). Surgical margins ranged from 1 to 10 mm (mean, 3.9 ± 1.4 mm). Negative surgical margins ranged 45 to 100 percent (mean, 86 ± 12 percent). Recurrence rates for 5-, 4-, 3-, and 2-mm surgical margins were 0.39, 1.62, 2.56, and 3.96 percent, respectively. Pooled data for incompletely excised margins have an average recurrence rate of 27 percent.
CONCLUSIONS: A 3-mm surgical margin can be safely used for nonmorpheaform basal cell carcinoma to attain 95 percent cure rates for lesions 2 cm or smaller. A positive pathologic margin has an average recurrence rate of 27 percent.
H Breuninger, K Dietz
Prediction of subclinical tumor infiltration in basal cell carcinoma.
J Dermatol Surg Oncol. 1991 Jul;17(7):574-8.
Abstract/Text
Two thousand-sixteen basal cell carcinomas (BCCs) were documented in terms of age, anatomic location, tumor diameter, initial excision depth, safety margin, histologic type, and the position of tumor outgrowths as determined by three-dimensional histologic study of the tumor margins in paraffin sections (micrographic surgery). The extent of each subsequent excision was recorded until tumor-free tissue was reached. The results showed that BCCs have a highly irregular infiltration pattern and a predilection for small, fingerlike outgrowths whose bases occupy 1-30 degrees of the tumor circumference. When superficial extension was expressed mathematically, the resulting exponential functions varied highly significantly (P = .001) according to histologic tumor type and diameter. The resulting curves permitted very precise prediction of the probability of tumor-positive margins (ie, subtotal excision), depending on the safety margin, histologic tumor type, and tumor diameter. For example, the probability of tumor-positive margins after excision of a BCC up to 10 mm in diameter is 30% with a safety margin of 2 mm, 16% with a safety margin of 3 mm, and 5% with a safety margin of 5 mm. The probability of tumor-positive margins for fibrosing primary BCCs 10-20 mm in diameter is 48, 34, and 18% with safety margins of 2, 3, and 5 mm, respectively. Recurrent tumors have a significantly higher probability of positive margins (P = .001) than primary ones. Anatomic location and tumor age affect subclinical extension only indirectly.
B Niederhagen, J J von Lindern, S Bergé, T Appel, R H Reich, E Krüger
Staged operations for basal cell carcinoma of the face.
Br J Oral Maxillofac Surg. 2000 Oct;38(5):477-9. doi: 10.1054/bjom.2000.0322.
Abstract/Text
211 patients (88 female, 123 male, mean age 63 years) presented with 279 basal cell carcinomas (191 primary tumours, 88 recurrent tumours) in the head and neck area that were excised. The resected margins were examined microscopically and the defect repaired at a second operation. The excision margin was 1-2 mm. The recurrence rate was 3%, which is lower than is achieved by other methods, and unaffected structures are optimally conserved.
Copyright 2000 The British Association of Oral and Maxillofacial Surgeons.
Rolf Hüsler, Fabian L Schlittler, Janett Kreutziger, Markus Streit, Andrej Banic, Franziska Schöni-Affolter, Robert E Hunger, Mihai A Constaninescu
Staged surgical therapy of basal cell carcinoma of the head and neck region: an evaluation of 500 procedures.
Swiss Med Wkly. 2008 Dec 13;138(49-50):746-51. doi: 2008/49/smw-12424.
Abstract/Text
UNLABELLED: QUESTIONS UNDER STUDY / PRINCIPLES: The surgical therapy of basal cell carcinoma (BCC) is especially demanding in the facial area. This retrospective study was undertaken to evaluate the outcome of staged surgical therapy (SST) of BCC of the head and neck region performed on an interdisciplinary basis at our institution.
METHODS: Patients treated for BCC in the head and neck area between 1/1/1997 and 31/12/2001 were included in the study. The lesions were histologically evaluated. Diameter of lesion, number of stages, defect coverage, operation time, and recurrence and infection rates were analysed using descriptive and inferential statistical procedures.
RESULTS: 281 patients were included in the study. SST was performed in two stages in 43.7%, in three stages in 12.9% and in four or more stages in 2.7%, depending on the type of tumour and the patient's pretreatment status. The total operating time per lesion averaged one hour. Defect coverage was achieved by direct closure (37.7%), by full thickness skin graft (39.5%), by split skin graft (1.1%), by local flaps (20.3%) or by composite grafts (1.1%). Median follow-up time was 58.5 months. Low rates of recurrence (3.6%) and infection (2%) were observed with this technique.
CONCLUSIONS: The staged surgical therapy of basal cell carcinoma evaluated here offers a series of advantages in respect of patient comfort and safety and economy, while allowing precise histological safety with low infection rates and reliable long-term results.
山田 聰、竹之内辰也、野本重敏、伊藤雅章, 手塚匡哉, 兼子泰行, 勝海薫：基底細胞癌に対する二期的手術の有用性．皮膚臨床 1999; 41(13): 2055-2058.
皮膚悪性腫瘍診療ガイドライン改訂委員会（基底細胞癌診療ガイドライングループ）：皮膚悪性腫瘍診療ガイドライン第3 版 基底細胞癌診療ガイドライン2021. 日皮会誌 2021;131:1467-96.
Claudia Auw-Haedrich, Stefanie Frick, Daniel Boehringer, Hans Mittelviefhaus
Histologic safety margin in basal cell carcinoma of the eyelid: correlation with recurrence rate.
Ophthalmology. 2009 Apr;116(4):802-6. doi: 10.1016/j.ophtha.2008.11.012. Epub 2009 Feb 20.
Abstract/Text
OBJECTIVE: To examine the correlation between the minimum histologic safety margin (HSM) and recurrence rate of periorbital basal cell carcinomas (BCC).
DESIGN: Cohort study.
PARTICIPANTS: One hundred one patients with 101 BCCs treated surgically between 1997 and 1999 at the eye hospital in Freiburg were enrolled in this study. Mean follow-up was 7 years (range, 104 days to 9.7 years).
METHODS: The tumors' minimum HSM was measured retrospectively in photographs of hematoxylin and eosin-stained paraffin slides using the digital picture analysis system AnalySIS of Soft Imaging System Inc, and/or calculated according to the tumor-free section number. Statistical analysis was performed using the Kaplan-Meier method and the log-rank test.
MAIN OUTCOME MEASURES: Histologic margins of solid and fibrous BCC and recurrence rate.
RESULTS: Seven of the 101 patients experienced tumor recurrence (6.93%) after a mean follow-up of 34.7 months (range, 3-83) according to Kaplan-Meier analysis. The patients were assigned to 1 of 3 groups: (I) those without HSM (n = 11), 3 recurrences (27.27%); (II) those with HSM <0.2 mm (n = 18), 3 recurrences (16.67%); and (III) those with HSM >0.2 mm (n = 72), 1 recurrence (1.39%). The difference in recurrences between those groups with HSM and HSM = 0, as well as between the HSM <0.2 mm-group and HSM >0.2 mm-group were statistically significant (P = 0.01; P = 0.03).
CONCLUSIONS: Extremely small HSMs are likely to prevent recurrences. At critical and visually easily accessible tumor sites (e.g., adjacent to the lacrimal puncta) a re-resection in solid BCCs with tumor-positive margins may not be mandatory, provided the surgical site is clinically inspected regularly. This conclusion does not apply to fibrous BCC.
R D Lovett, C A Perez, S J Shapiro, D M Garcia
External irradiation of epithelial skin cancer.
Int J Radiat Oncol Biol Phys. 1990 Aug;19(2):235-42.
Abstract/Text
A total of 339 consecutively treated, biopsy proven squamous and basal cell carcinomas of the skin treated from January 1966 to December 1986 were retrospectively analyzed to determine the patterns of local recurrence. There were 242 basal cell carcinomas, 92 squamous cell carcinomas, and 5 variants of squamous cell carcinoma in various locations. Radiotherapy was the initial treatment modality in 212 patients and 127 were treated after failing initial surgical excision. Lymph nodes were involved in 1/242 patients (.4%) with basal cell carcinoma, 14/92 patients (15%) with initially treated squamous cell carcinoma, and 20/51 (39%) with recurrent squamous cell lesions. Distant metastasis was found in one patient. Superficial X rays were given to 187 patients, electrons to 57 patients, megavoltage photons to 15, and a combination of modalities to the remainder. Overall local tumor control was achieved in 292 of 339 patients (86%), 220 of 242 (91%) with basal cell and 73 of 97 (75%) with squamous cell carcinoma. Tumor control was closely related to the size of the primary lesion. For lesions less than 1 cm tumor control was 97% (86/89) for basal cell and 91% (21/23) for squamous cell carcinoma. For 1 to 5 cm, tumor control was 87% (116/133) for basal cell and 76% (39/51) for squamous cell carcinoma and for lesions greater than 5 cm, the tumor control was 87% (13 of 15) and 56% (9/16), respectively. Tumor control was related to the modality used to treat the patient in spite of stratification of primary lesion size. For superficial X rays, tumor control was 98% (81/83) for lesions less than 1 cm, 93% (94/101) for lesions 1-5 cm and 100% (5/5) for lesions greater than 5 cm. For electrons tumor control was 88% (14/16), 72% (23/32), and 78% (7/9), respectively. For mixed beams tumor control was 90% (9/10), 76% (32/42), and 64% (9/14), respectively, and for 60Co-4 MV X rays, tumor control was 100% (3/3), 67% (6/9), and 33% (1/3), respectively. Cosmesis and complications were analyzed in 261 patients. An excellent or good cosmetic result was found in 92% (239/261) of the patients. There were 8 of 261 patients (3.1%) with fair and 19 of 261 (7.3%) with poor cosmesis. Cosmesis had an inverse relation to the primary lesion size with 97 of 99 patients (98%) with tumors 1 cm or less, 123 of 140 patients (88%) with lesions 1 to 5 cm and 13 of 16 patients (82%) with larger tumors having excellent or good cosmetic results. Cosmesis is also related to treatment modality.(ABSTRACT TRUNCATED AT 400 WORDS)
Maud H E Jansen, Klara Mosterd, Aimee H M M Arits, Marieke H Roozeboom, Anja Sommer, Brigitte A B Essers, Han P A van Pelt, Patricia J F Quaedvlieg, Peter M Steijlen, Patty J Nelemans, Nicole W J Kelleners-Smeets
Five-Year Results of a Randomized Controlled Trial Comparing Effectiveness of Photodynamic Therapy, Topical Imiquimod, and Topical 5-Fluorouracil in Patients with Superficial Basal Cell Carcinoma.
J Invest Dermatol. 2018 Mar;138(3):527-533. doi: 10.1016/j.jid.2017.09.033. Epub 2017 Oct 16.
Abstract/Text
For the treatment of superficial basal cell carcinoma, a prospective, noninferiority, randomized controlled multicenter trial with 601 patients showed that 5% imiquimod cream was superior and 5-fluorouracil cream not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) at 1 and 3 years after treatment. No definite conclusion could be drawn regarding the superiority of imiquimod over 5-fluorouracil. We now present the 5-year follow-up results according to the intention-to-treat analysis. Five years after treatment, the probability of tumor-free survival was 62.7% for methyl aminolevulinate photodynamic therapy (95% confidence interval [CI] = 55.3-69.2), 80.5% for imiquimod (95% CI = 74.0-85.6), and 70.0% for 5-fluorouracil (95% CI = 62.9-76.0). The hazard ratio for treatment failure of imiquimod and 5-fluorouracil were 0.48 (95% CI = 0.32-0.71, P < 0.001) and 0.74 (95% CI = 0.53-1.05, P = 0.09), respectively, when compared with methyl aminolevulinate photodynamic therapy. Compared with 5-fluorouracil, imiquimod showed a hazard ratio of 0.65 (95% CI 0.43-0.98, P = 0.04). In conclusion, 5 years after treatment, the results of this trial show that 5% imiquimod cream is superior to both methyl aminolevulinate photodynamic therapy and 5-fluorouracil cream in terms of efficacy for superficial basal cell carcinoma. We therefore consider 5% imiquimod cream as the first choice for noninvasive treatment in most primary superficial basal cell carcinomas.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Hywel C Williams, Fiona Bath-Hextall, Mara Ozolins, Sarah J Armstrong, Graham B Colver, William Perkins, Paul S J Miller, Surgery Versus Imiquimod for Nodular and Superficial Basal Cell Carcinoma (SINS) Study Group
Surgery Versus 5% Imiquimod for Nodular and Superficial Basal Cell Carcinoma: 5-Year Results of the SINS Randomized Controlled Trial.
J Invest Dermatol. 2017 Mar;137(3):614-619. doi: 10.1016/j.jid.2016.10.019. Epub 2016 Dec 5.
Abstract/Text
We previously reported modest clinical 3-year benefit for topical imiquimod compared with surgery for superficial or nodular basal cell carcinoma at low-risk sites in our noninferiority randomized controlled SINS trial. Here we report 5-year data. Participants were randomized to imiquimod 5% cream once daily (superficial basal cell carcinoma, 6 weeks; nodular basal cell carcinoma, 12 weeks) or excisional surgery (4-mm margin). The primary outcome was clinical absence of initial failure or signs of recurrence at the 3-year dermatology review. Five-year success was defined as 3-year success plus absence of recurrences identified through hospital, histopathology, and general practitioner records. Of 501 participants randomized, 401 contributed to the modified intention-to-treat analyses at year 3 (primary outcome), 383 (96%) of whom had data at year 5. Five-year success rates for imiquimod were 82.5% (170/206) compared with 97.7% (173/177) for surgery (relative risk of imiquimod success = 0.84, 95% confidence interval = 0.77-0.91, P < 0.001). These were comparable to year 3 success rates of 83.6% (178/213) and 98.4% (185/188) for imiquimod and surgery, respectively. Most imiquimod treatment failures occurred in year 1. Although surgery is clearly superior to imiquimod, this study shows sustained benefit for lesions that respond early to topical imiquimod.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Aleksandar Sekulic, Michael R Migden, Nicole Basset-Seguin, Claus Garbe, Anja Gesierich, Christopher D Lao, Chris Miller, Laurent Mortier, Dedee F Murrell, Omid Hamid, Jorge F Quevedo, Jeannie Hou, Edward McKenna, Natalie Dimier, Sarah Williams, Dirk Schadendorf, Axel Hauschild, ERIVANCE BCC Investigators
Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study.
BMC Cancer. 2017 May 16;17(1):332. doi: 10.1186/s12885-017-3286-5. Epub 2017 May 16.
Abstract/Text
BACKGROUND: In the primary analysis of the ERIVANCE BCC trial, vismodegib, the first US Food and Drug Administration-approved Hedgehog pathway inhibitor, showed objective response rates (ORRs) by independent review facility (IRF) of 30% and 43% in metastatic basal cell carcinoma (mBCC) and locally advanced BCC (laBCC), respectively. ORRs by investigator review were 45% (mBCC) and 60% (laBCC). Herein, we present long-term safety and final investigator-assessed efficacy results in patients with mBCC or laBCC.
METHODS: One hundred four patients with measurable advanced BCC received oral vismodegib 150 mg once daily until disease progression or intolerable toxicity. The primary end point was IRF-assessed ORR. Secondary end points included ORR, duration of response (DOR), progression-free survival, overall survival (OS), and safety.
RESULTS: At data cutoff (39 months after completion of accrual), 8 patients were receiving the study drug (69 patients in survival follow-up). Investigator-assessed ORR was 48.5% in the mBCC group (all partial responses) and 60.3% in the laBCC group (20 patients had complete response and 18 patients had partial response). ORRs were comparable across patient subgroups, including aggressive histologic subtypes (eg, infiltrative BCC). Median DOR was 14.8 months (mBCC) and 26.2 months (laBCC). Median OS was 33.4 months in the mBCC cohort and not estimable in the laBCC cohort. Adverse events remained consistent with clinical experience. Thirty-three deaths (31.7%) were reported; none were related to vismodegib.
CONCLUSIONS: This long-term update of the ERIVANCE BCC trial demonstrated durability of response, efficacy across patient subgroups, and manageable long-term safety of vismodegib in patients with advanced BCC.
TRIAL REGISTRATION: This study was registered prospectively with Clinicaltrials.gov , number NCT00833417 on January 30, 2009.
N Basset-Séguin, A Hauschild, R Kunstfeld, J Grob, B Dréno, L Mortier, P A Ascierto, L Licitra, C Dutriaux, L Thomas, N Meyer, B Guillot, R Dummer, P Arenberger, K Fife, A Raimundo, E Dika, N Dimier, A Fittipaldo, I Xynos, J Hansson
Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial.
Eur J Cancer. 2017 Nov;86:334-348. doi: 10.1016/j.ejca.2017.08.022. Epub 2017 Nov 5.
Abstract/Text
BACKGROUND: The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib-a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)-in a patient population representative of clinical practice. Primary analysis data are presented.
PATIENTS AND METHODS: Patients with locally advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points.
RESULTS: Evaluable adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0-44) months. Most patients (98%) had ≥1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure ≥12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7-71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6-48.1) in patients with metastatic BCC.
CONCLUSIONS: The primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. CLINICALTRIALS.GOV: NCT01367665.
Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
F Reymann
Treatment of basal cell carcinoma of the skin with 5-fluorouracil ointment. A 10-year follow-up study.
Dermatologica. 1979;158(5):368-72.
Abstract/Text
During the period 1966-1968, 88 patients with a total of 95 basal cell carcinomas were treated with 5% 5-fluorouracil ointment. A follow-up study carried out from November 1977 to January 1978 revealed a total of 12 recurrences in 56 surviving patients with 56 basal cell carcinomas. The recurrence rate is thus 21.4%. It is concluded that there is hardly any indication for using 5-fluorouracil in local treatment of nodular basal cell carcinoma.
E Klein, H L Stoll, H Milgrom, F Helm, M J Walker
Tumors of the skin. XII. Topical 5-Fluorouracil for epidermal neoplasms.
J Surg Oncol. 1971;3(3):331-49.
Abstract/Text
H Ebner
Treatment of skin epitheliomas with 5-fluorouracil (5-FU) ointment. Influence of therapeutic design on recurrence of lesions.
Dermatologica. 1970;140:Suppl 1:42-6.
Abstract/Text
R Romagosa, L Saap, M Givens, A Salvarrey, J L He, S L Hsia, J R Taylor
A pilot study to evaluate the treatment of basal cell carcinoma with 5-fluorouracil using phosphatidyl choline as a transepidermal carrier.
Dermatol Surg. 2000 Apr;26(4):338-40.
Abstract/Text
BACKGROUND: In certain situations, successful topical therapy of basal cell carcinoma (BCC) without the inconvenience, risk, and expense of surgery would be of great value to patients. Placing 5-fluorouracil (FU) in an appropriate carrier may solve these problems. Phosphatidyl choline (PC) penetrates effectively throughout the epidermis of shaved rabbits and may be able to carry small water-soluble molecules such as nucleotides across lipid barriers when applied topically.
OBJECTIVE: We propose that employing PC as a vehicle will facilitate the penetration of 5-FU and increase efficacy as compared to petrolatum-based 5-FU cream.
METHODS: This pilot study is a double-blinded and randomized therapeutic trial. Thirteen patients with 17 biopsy-proven, moderate thickness BCCs were randomized to receive either cream A (5% 5-FU in a PC vehicle) or cream B (Efudex(R): 5% 5-FU in a petrolatum base). Patients applied cream A or cream B twice a day for 4 weeks. The patients underwent an excisional biopsy of the treated BCC site at week 16.
RESULTS: There was a 90% cure rate (9/10) in those lesions treated with 5% 5-FU in PC cream and a 57% cure rate (4/7) in those treated with 5% 5-FU in a petrolatum-based cream.
CONCLUSION: Although the study was unable to detect any statistically significant differences in outcome between the study groups, this small pilot study shows preliminary findings which may indicate an increase in the short-term eradication of BCC using a PC-based vehicle as compared to conventional petrolatum-based formulations.
V L Hall, B J Leppard, J McGill, M E Kesseler, J E White, P Goodwin
Treatment of basal-cell carcinoma: comparison of radiotherapy and cryotherapy.
Clin Radiol. 1986 Jan;37(1):33-4.
Abstract/Text
A prospective randomised trial to compare radiotherapy and cryotherapy in the treatment of basal-cell carcinomas was carried out in 93 patients. Two years after treatment, 4% of tumours treated with radiotherapy and 39% of those treated with cryotherapy had recurred. It is concluded that cryotherapy does not offer a satisfactory alternative to radiotherapy in the treatment of basal-cell carcinomas.
John Geisse, Ivor Caro, Jane Lindholm, Loren Golitz, Patti Stampone, Mary Owens
Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies.
J Am Acad Dermatol. 2004 May;50(5):722-33. doi: 10.1016/j.jaad.2003.11.066.
Abstract/Text
BACKGROUND: Imiquimod is an immune response modifier that is a Toll-like receptor 7 agonist that induces interferon and other cytokines through the innate immune system and stimulates cell-mediated immunity through T cells. Imiquimod has been shown to be efficacious as a topical treatment for basal cell carcinoma (BCC).
OBJECTIVE: We sought to evaluate the efficacy and safety of imiquimod 5% cream compared with vehicle for treating superficial BCC (sBCC).
METHODS: Two identical studies were conducted. Subjects with one sBCC were dosed with imiquimod or vehicle cream once daily 5 or 7x/week for 6 weeks in these 2 randomized, double-blind, vehicle-controlled Phase III studies. The lesion site was clinically examined 12 weeks posttreatment and then excised for histological evaluation.
RESULTS: Data from both studies were pooled. Composite clearance rates (combined clinical and histological assessments) for the 5 and 7x/week imiquimod groups were 75% and 73%, respectively. Histological clearance rates for the 5 and 7x/week imiquimod groups were 82% and 79%, respectively. Increasing severity of erythema, erosion, and scabbing/crusting was associated with higher clearance rates.
CONCLUSION: Imiquimod appears to be safe and effective for the treatment of sBCC when compared with vehicle cream. The difference in clearance rates between the two imiquimod dosing groups was not significant. The 5x/week regimen is recommended.
H J Schulze, B Cribier, L Requena, J Reifenberger, C Ferrándiz, A Garcia Diez, V Tebbs, S McRae
Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe.
Br J Dermatol. 2005 May;152(5):939-47. doi: 10.1111/j.1365-2133.2005.06486.x.
Abstract/Text
BACKGROUND: Imiquimod is an immune response modifier that acts through toll-like receptor 7 to induce cytokine production and a subsequent innate and adaptive cell-mediated immune response. Clinical studies have demonstrated clinical and histological clearance of superficial basal cell carcinoma (sBCC) after treatment with imiquimod 5% cream.
OBJECTIVES: To evaluate the safety and clinical efficacy of imiquimod (Aldaratrade mark; 3M Pharmaceuticals, St Paul, MN, U.S.A.) 5% cream for the treatment of sBCC in a multicentre, randomized, parallel, vehicle-controlled, double-blind, phase III clinical study conducted at 26 centres in Europe.
METHODS: Subjects who had at least one histologically confirmed sBCC tumour were randomized to apply imiquimod or vehicle cream to the target tumour once daily, seven times per week (7 x/week) for 6 weeks. The target tumour location was identified with an indelible ink mark before treatment initiation. The treated tumour site was clinically assessed for treatment response at 12 weeks post-treatment and was then excised for histological evaluation. Efficacy assessments included the composite response rates (proportion of subjects with clinical and histological clearance) and response rates solely based on histology (proportion of subjects with histological clearance). Safety assessments, which included adverse events and scoring of local skin reactions (LSRs), were carried out throughout the study.
RESULTS: In total, 166 subjects were enrolled in this study. For the intent-to-treat dataset, there was a statistically significant difference between imiquimod and vehicle groups for both composite clearance rates (clinical and histological assessments) and histological clearance rates. Composite clearance was demonstrated in 77% and 6% of subjects treated with imiquimod and vehicle cream, respectively. Histological clearance was demonstrated in 80% and 6% of subjects treated with imiquimod and vehicle cream, respectively. The most frequently reported safety findings were investigator-assessed LSRs and spontaneous reports by subjects of application site reactions, which occurred more frequently in the imiquimod group than in the vehicle group.
CONCLUSIONS: Imiquimod 5% cream administered 7 x/week for 6 weeks is a safe and effective treatment for sBCC when compared with vehicle cream.
Harald Gollnick, Carlos Guillén Barona, Ronald Gj Frank, Thomas Ruzicka, Mosaad Megahed, Joachim Maus, Ullrich Munzel
Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term follow-up study in Europe.
Eur J Dermatol. 2008 Nov-Dec;18(6):677-82. doi: 10.1684/ejd.2008.0519. Epub 2008 Oct 27.
Abstract/Text
Imiquimod 5% cream is an immune response modifier approved for the treatment of superficial basal cell carcinoma (sBCC) once daily, 5 x per week for 6 weeks. This report reveals the final results of a 5-year follow-up study to evaluate the recurrence rate of sBCCs treated with imiquimod. As previously reported, 182 patients were enrolled in the study and 163 (89.6%) had no clinical evidence of their target sBCC at the 12-week post-treatment assessment; these 163 were followed for up to 5 years. During the follow-up period, 18 clinical recurrences occurred at the target tumour site, 8 and 10 of which occurred during the first 6 and 12 months of follow-up, respectively. The 5-year Kaplan-Meier and life-table estimates for sustained clinical clearance of those patients initially cleared were 84.5% and 86.9%, respectively, and 90.3% considering histology. The estimate of overall treatment success for all treated patients at the end of follow-up was 77.9% (80.9% considering histology). The data support clinical assessment of initial response as predictive of long-term outcome. Most of the recurrences occurred early, indicating that careful follow-up is important during the first year after treatment.
