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Adjuvant therapy has not improved survival in metastatic basal cell carcinoma
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Overall prognosis in patients with metastatic basal cell carcinoma has remained poor during the past 3 decades, although nearly half of patients received adjuvant chemotherapy or radiation during that time, according to results of a retrospective review.
Ashley Wysong, MD, MS, a dermatology resident physician in the department of dermatology at Stanford University, and colleagues evaluated all published metastatic basal cell carcinoma (MBCC) cases published from 1981 to 2011.
They identified changes in tumor characteristics and patient demographics since the completion of a previous review by von Domarus and colleagues, which spanned from 1894 to 1980. Wysong and colleagues also evaluated whether adjuvant therapy had extended survival in this patient population.
The researchers identified 238 cases, and 194 were included in the analysis.
Most patients (n=136; 71%) were men. Median age at onset of primary tumor was 50 years (range, 24-88).
The average primary tumor size of 7.5 cm. Primary tumors most frequently developed on the head and neck (64%) and trunk (21%).
The most common sites of metastases were the regional lymph nodes (53%), lungs (33%) and bone (20%). Researchers reported an increased number of MBCCs arose from the ear and scalp (P<.05) or genitalia (P=.04) compared with the previous review by von Domarus and colleagues.
Median time from primary tumor development to first indication of metastasis was 9 years, Wysong and colleagues reported.
About one-quarter (n=51) of cases included survival data. They showed a median 10-month survival after diagnosis of metastasis (range, 0.5-108) compared with 8 months in the review by von Domarus and colleagues, a difference that was not statistically significant.
“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,” Wysong and colleagues wrote.
Eighty cases (44%) documented use of adjuvant therapy. The most common adjuvant therapy was radiation (54%), followed by chemotherapy (28%), and radiation plus chemotherapy (18%).
Outcomes of cases that reported survival data showed median survival among patients who underwent adjuvant therapy was similar to that of patients who did not undergo adjuvant therapy (11 months vs. 10 months). The survival differences did not differ based on type of adjuvant therapy, tumor size, patient sex, age at onset or time prior to metastasis. Adjuvant therapy also was associated with similar outcomes regardless of whether patients exhibited distant or local metastasis.
“These data suggest that radiation and chemotherapy have not significantly improved MBCC survival ... although the sample size may contribute to a lack of power to detect a difference in this rare condition,” Wysong and colleagues concluded.
The findings highlight the traditional poor response of MBCC to conventional therapies, suggesting hedgehog pathway inhibitors such as vismodegib (Erivedge, Genentech) — a first-in-class small-molecule hedgehog pathway inhibitor approved in 2012 for treatment of metastatic and locally advanced BCC — will be an important therapeutic approach, Kelly L. Harms, MD, PhD, and Andrzej A. Dlugosz, MD, both of the department of dermatology at the University of Michigan, wrote in an accompanying editorial.
“The availability of vismodegib and other hedgehog pathway antagonists is a welcome — and in some cases life-saving — development for our patients with the most advanced forms of basal cell carcinoma and likely other hedgehog-driven malignancies,” Harms and Dlugosz wrote. “Clinical use of these agents, coupled with bench-based research, will help address many remaining issues regarding the responsiveness of different basal cell carcinoma subtypes, overcoming inherent or acquired drug resistance, eliminating residual dormant tumor cells, potential utility as neoadjuvant therapy before Mohs’ surgery, efforts to override adverse effects, and efficacy of topical formulations. While vismodegib and other hedgehog pathway antagonists will likely play an important role in the management of metastatic and inoperable basal cell carcinoma, additional studies will determine how other patients with less advanced forms of basal cell carcinoma can benefit from this therapy.”
References:
Harms KL. JAMA Dermatol. 2013;149:607-608.
Wysong A. JAMA Dermatol. 2013;149:615-616.