Update on advanced basal cell carcinoma diagnosis and treatment (original) (raw)

Basal cell carcinoma (BCC) is the most commonly diagnosed cancer and the most common skin cancer in the world 1-5. Despite increased insight on skin cancer risk factors, including excessive sun exposure and indoor tanning, the incidence of skin cancer continues to rise worldwide, particularly in younger populations 6. In a recent study, it was estimated that more than four million cases are diagnosed annually in the United States alone 6. Given the widespread prevalence of this disease, there is a substantial impact on overall patient morbidity and quality of life 7-9. Similarly, medical treatment for skin cancer accounts for a considerable amount of healthcare expenditures and is often a large financial burden to patients and their families. As such, improved screening and treatment options are imperative to reduce the cost and to refine the outcome of this rising problem. Current treatment for simple BCC The prognosis for most patients with BCC is good as these tumors are generally slow growing and amenable to treatment if found early. There is much literature on the treatment of superficial BCCs with non-surgical therapies 10-11. These treatments are generally well tolerated, with adverse effects limited to the treatment site. The majority of other BCC subtypes are treated with surgery 10-11. Radiation therapy provides an alternative treatment option for some patients who do not desire surgery. However, radiation is associated with many adverse effects, including tissue necrosis, skin atrophy, and new primary tumor development 12. In addition, the cosmetic results of radiation can worsen over time, making this a less attractive option 10-12. With these drawbacks, radiation therapy is not recommended for patients under 50 years of age. Complex cases of BCC Despite the fact that the majority of BCCs are rarely fatal, a small subset can become destructive with significant tissue involvement 11. Traditionally, advanced BCC refers to lesions that are invasive or metastatic, and not amenable to surgical or radiation therapy 11. Recurrent BCCs are also considered complex, especially in patients with inherited conditions resulting in multiple tumors. Clinical management of these advanced BCCs is complicated as nonsurgical approaches are usually inadequate, and surgical management can result in considerable deformity. Fortunately, by definition these complex cases are extremely uncommon, with locally advanced disease accounting for 0.8% of all BCC and metastatic disease for 0.04% 13. Many of these patients are in the geriatric age range with multiple medical comorbidities, thus at times a palliative, or a 'watch and wait' approach, is taken. However, for patients who do seek treatment, options are limited. Until recently, no systemic therapy was approved for advanced BCC, and patients were treated mainly with cisplatin alone or in combination with other chemotherapies 14. These were associated with many unfavorable side effects and limited efficacy. There now exists an alternative targeted therapy, specifically inhibitors of the hedgehog-signaling pathway, which serves as an option for these patients. New treatment options Molecular studies have shown that more than 90% of patients with BCC have a mutation in the hedgehog-signaling pathway 15. Usually, this mutation causes loss of function of patched homologue 1 (PTCH1),