Nonsurgical Treatment Options for Basal Cell Carcinoma - Focus on Advanced Disease

December 2013 | Volume 12 | Issue 12 | Original Article | 1369 | Copyright © 2013

Gary Goldenberg MDa and Omid Hamid MDb

aIcahn School of Medicine at Mount Sinai, New York, NY
bThe Angeles Clinic and Research Institute, Los Angeles, CA

Abstract

Basal cell carcinoma (BCC) is the most common cancer in the world. It is typically slow growing and usually effectively managed with surgery. However, BCCs in some patients are unsuitable for surgery or the patient may prefer a nonsurgical treatment. Radiotherapy is a nonsurgical option for the primary treatment of either low- or high-risk BCCs. It is associated with high cure rates, albeit somewhat lower than those observed with Mohs micrographic surgery for high-risk BCCs. Not all patients with BCCs are suitable for radiotherapy. Superficial therapies for BCC include topical imiquimod or 5- fluorouracil and photodynamic therapy (PDT). These therapies are generally associated with somewhat lower clearance rates and/or higher recurrence rates than surgery or radiotherapy, although they may be suitable in patients with low-risk BCCs when surgery or radiotherapy are impractical or less appropriate. An appealing feature of PDT is excellent cosmesis, but PDT is not currently approved by the Food and Drug Administration (FDA), and regimens are not well standardized. Vismodegib is a first-in-class hedgehog pathway inhibitor and recent addition to the armamentarium for the treatment of advanced BCC.

J Drugs Dermatol. 2013;12(12):1371-1378.

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INTRODUCTION

Basal cell carcinoma (BCC) is the most common cancer worldwide.1-3 Based on National Cancer Institute estimates of nonmelanoma skin cancer, more than 1.5 million new cases of BCC were diagnosed in the United States in 2012.4 The incidence of BCC has been rising in the United States and other countries in recent decades,5-8 particularly in younger women.8 Rising incidence combined with the costs of BCC management6,9 makes BCC a significant health problem both in terms of patient well-being and overall healthcare expenditures.10

BCCs are generally slow-growing tumors without significant extension.2,11 With early intervention, most low-to-moderate risk BCCs can be treated surgically with 5-year cure rates above 95%.12-14 However, either because the patient postpones medical care or for other reasons, some BCCs become locally aggressive or, more rarely, metastasize distally. A significant percentage of these tumors are not amenable to surgical treatment options. Nonsurgical management approaches are sometimes chosen for less aggressive, low-risk BCCs as well.

This third in a series of 3 CME articles examines nonsurgical approaches to BCC, with particular focus on the management of advanced BCCs. The first installment (published in the October 2013 issue) examined new agents for BCC and their mechanism of action. The second installment (published in the November 2013 issue) reviewed risk factors for recurrent or advanced BCC, and management choices based on lowor high-risk tumors.

Overview of BCC Management and Nonsurgical Options

The aim of BCC treatment is complete tumor eradication that prevents or reduces recurrence while providing optimal cosmesis and quality of life.15-17 Treatment is largely based on risk of BCC recurrence or progression to advanced disease.15,17 Factors associated with higher recurrence risk include histological type (morpheaform, infiltrative, micronodular, or basosquamous), tumor size and depth, tumor location (midface, nose, ears, or scalp), poorly defined tumor borders, perineural or vascular involvement, recurrence despite optimal treatment, prior radiation treatment/exposure, older age, male gender, and (for patients undergoing surgery) positive excision margins.18-25 Risk factors for metastasis appear to be similar to those for recurrence, 23,25-31 although neglect (persistent BCC of many years duration without treatment) should be added as the strongest risk factor for metastatic BCC (mBCC).23,25,28,29 Considerations besides risk of recurrence or advanced disease that may affect treatment choice in particular cases include likelihood of disfigurement or reduced quality of life with one as opposed to another treatment option, patient preference or suitability, treatment costs, and availability of local services.16,21,24

According to the most recent National Clinical Practice Network (NCCN) guidelines for BCC, suitable primary treatment for lowrisk BCCs most often includes a surgical approach, although radiotherapy or (less often) photodynamic therapy may be a better option in some patients.15 Since surgical options were

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