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Figure. Number of cases of metastatic basal cell carcinoma (mBCC) reported in the literature from 1894 to 2011.

Figure. Number of cases of metastatic basal cell carcinoma (mBCC) reported in the literature from 1894 to 2011.

Table 1. Characteristics of Metastatic Basal Cell Carcinoma Cases
Table 1. Characteristics of Metastatic Basal Cell Carcinoma Cases
Table 2. Characteristics of 51 Metastatic Basal Cell Carcinoma Cases With Survival Data by Whether Adjuvant Therapy Was Receiveda
Table 2. Characteristics of 51 Metastatic Basal Cell Carcinoma Cases With Survival Data by Whether Adjuvant Therapy Was Receiveda
1.
Rogers HW, Weinstock MA, Harris AR,  et al.  Incidence estimate of nonmelanoma skin cancer in the United States, 2006.  Arch Dermatol. 2010;146(3):283-287PubMedArticle
2.
von Domarus H, Stevens PJ. Metastatic basal cell carcinoma: report of five cases and review of 170 cases in the literature.  J Am Acad Dermatol. 1984;10(6):1043-1060PubMedArticle
3.
Lattes R, Kessler RW. Metastasizing basal-cell epithelioma of the skin: report of two cases.  Cancer. 1951;4(4):866-878PubMedArticle
4.
Sekulic A, Migden MR, Oro AE,  et al.  Efficacy and safety of vismodegib in advanced basal-cell carcinoma.  N Engl J Med. 2012;366(23):2171-2179PubMedArticle
Research Letter
May 2013

Update on Metastatic Basal Cell Carcinoma: A Summary of Published Cases From 1981 Through 2011

Author Affiliations

Author Affiliations: Department of Dermatology, Stanford University School of Medicine, Stanford, California.

JAMA Dermatol. 2013;149(5):615-616. doi:10.1001/jamadermatol.2013.3064

While basal cell carcinoma (BCC) is the most common cancer in the United States,1 metastasis (mBCC) is extremely rare, with an incidence of 0.0028% to 0.55%.2 The most recent review of mBCC cases from 1894 through 1980 by von Domarus and Stevens2 is now 30 years old. We conducted a retrospective systematic evaluation of all published mBCC cases from 1981 through 2011 to update patient demographics and tumor characteristics associated with mBCC and to determine whether adjuvant therapy was associated with improved survival.

Methods

An extensive literature search was performed for all published cases of sporadic mBCC from 1981 to 2011. We defined mBCC using the Lattes and Kessler3 criteria, and 238 cases were identified. Forty-four cases were excluded (20 were not in English, 4 were published more than once, 5 were in patients with basal cell nevus syndrome, 2 were in immunocompromised individuals, and 13 did not meet criteria for mBCC), for a total of 194 cases. Two-sided Pearson χ2 and nonparametric tests were used to compare percentages and medians of variables in this review compared with the 1984 review by von Domarus and Stevens.2 This study was exempt from the institutional review board of Stanford University.

Results

Most of the 194 mBCC cases arose in white males with a median age of 50 years (Table 1). The average size of primary tumors was 7.5 cm, occurring most commonly on the head and neck (64%) and trunk (21%). More mBCCs arose from the scalp and ear (P < .05) or from the genitalia (P = .04) compared with the prior review. The BCCs most commonly metastasized to the regional lymph nodes (53%), lungs (33%), and bone (20%). There was a significant increase in the proportion of metastatic cases involving the regional lymph nodes (54% vs 39%; P = .01).

The median time between primary tumor and the first sign of metastasis was 9 years. Of the 51 cases with survival data (26%), the median survival after diagnosis of metastasis was 10 months (range, 0.5-108.0 months), which was not statistically different than 8 months previously reported. Of those who survived less than 1 year, 26% had metastases on initial presentation with an average neglect of treatment of the primary tumor of over 10 years prior to presentation and a larger primary tumor size (13.9 cm vs 7.5 cm; P = .01). However, there were no significant differences in sex, age at onset, or local vs distant metastasis (Table 2).

Forty-four percent of cases (80 of 194) reported the use of adjuvant therapies: 54%, radiation; 28%, chemotherapy; and 18%, both radiation and chemotherapy. The most common chemotherapy regimens included cisplatin (66%), bleomycin (22%), fluorouracil, 5% cream(17%), and carboplatin (14%). Of note, in cases in which survival data were available (n = 51), median survival of individuals who received adjuvant therapy (11 months [range, 1-108 months]) was similar to survival in those who did not receive adjuvant therapy (10 months [range, 0.5-96.0 months]), despite type of adjuvant received, sex, age at onset, tumor size, interval before metastasis, and local vs distant metastasis.

Discussion

We report 194 cases of mBCC from 1981 through 2011 for a total of 364 cases from 1894 through 2011; the number of mBCC cases seems to be increasing (Figure). This increase may simply be publication bias; however, it parallels the well-established climbing incidence of sporadic BCCs.1 Most cases of mBCC were reported in adult white males, originating from large tumors (7.5 cm) on the head and neck, and spreading to the lymph nodes. In patients who survived less than 1 year after diagnosis, the tumor was significantly larger with an average neglect to seek medical care of 10 years, suggesting the importance of tumor size and delay of treatment in overall prognosis.

Our updated review suggests that the overall prognosis of mBCC continues to be poor, with a median survival of 10 months, despite 44% of patients with mBCC receiving adjuvant chemotherapy or radiation in the past 30 years. These data suggest that radiation and chemotherapy have not significantly improved mBCC survival regardless of age, sex, tumor size, or local vs distant metastasis, although the small sample size may contribute to a lack of power to detect a difference in this rare condition. Our results may be particularly important as historic controls to compare any survival benefit from novel hedgehog pathway inhibitors, such as vismodegib.4 With the continued development of targeted therapies for BCC, we will likely see changes in the way we manage mBCC that may improve disease-free and overall survival.4

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Article Information

Correspondence: Dr Wysong, Department of Dermatology, Stanford University, 450 Broadway St, Pavilion C, Second Floor, Redwood City, CA 94063 (awysong@stanford.edu).

Accepted for Publication: November 27, 2012.

Author Contributions: Drs Wysong and Tang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Wysong and Tang. Acquisition of data: Wysong. Analysis and interpretation of data: All authors. Drafting of the manuscript: Wysong and Tang. Critical revision of the manuscript for important intellectual content: Aasi and Tang. Statistical analysis: Wysong. Administrative, technical, and material support: Wysong and Tang.

Conflict of Interest Disclosures: None reported.

References
1.
Rogers HW, Weinstock MA, Harris AR,  et al.  Incidence estimate of nonmelanoma skin cancer in the United States, 2006.  Arch Dermatol. 2010;146(3):283-287PubMedArticle
2.
von Domarus H, Stevens PJ. Metastatic basal cell carcinoma: report of five cases and review of 170 cases in the literature.  J Am Acad Dermatol. 1984;10(6):1043-1060PubMedArticle
3.
Lattes R, Kessler RW. Metastasizing basal-cell epithelioma of the skin: report of two cases.  Cancer. 1951;4(4):866-878PubMedArticle
4.
Sekulic A, Migden MR, Oro AE,  et al.  Efficacy and safety of vismodegib in advanced basal-cell carcinoma.  N Engl J Med. 2012;366(23):2171-2179PubMedArticle
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