The emerging science of field cancer is changing the paradigm for diagnosing and treating skin cancer by targeting entire skin regions. Dermatologic surgeon Sean R. Christensen, MD, PhD, addressed the most recent scientific insights Saturday during “Field Cancerization and Multiple SCC: New Molecular Insights and Evidence-Based Clinical Management” (U037).
“Squamous cell carcinoma (SCC) often presents not as a single lesion, but as multiple lesions within an area or ‘field’ where genetic damage has occurred, usually from sunlight exposure,” said Dr. Christensen, assistant professor of dermatology at Yale University School of Medicine. “Approaching SCC lesion-by-lesion is not really effective and is failing our patients with multiple lesions.”
Recent genetic sequencing technology has enabled researchers to prove the concept of field cancer by discovering that the same mutations driving SCC development also arise in normal-appearing skin within the same field as SCC lesions. Treating only visible skin cancers ignores precancerous changes of skin in the same field.
Exposure to the sun’s ultraviolet rays is the prime culprit triggering genetic mutations that lead to SCC. Researchers have discovered a particular type of signature genetic lesion seen in skin cancer caused by ultraviolet light, Dr. Christensen said. Not only does ultraviolet light produce the genetic insult causing skin cancer, but it also stimulates SCC precursors to grow and progress. Heavy sun exposure, a history of previous SCCs, the presence of precancerous actinic keratoses, and taking immunosuppressives for organ transplantation all are risk factors for the development of multiple SCCs within a genetically damaged field.
Rigorous sun protection and a treatment ladder are Dr. Christensen’s proposed strategies for addressing field cancer in the setting of multiple SCCs.
“Any treatment directed at field cancer needs to occur in combination with rigorous sun protection,” he said. “There is data to show that sun protection alone can decrease the formation of new skin cancers. It’s a zero-risk therapy.”
The field cancer treatment ladder starts with milder but effective therapies and then advances to more aggressive treatments as indicated. The first level calls for topical treatments, such as 5-fluorouracil, imiquimod, or ingenol mebutate. Although none of these medications are approved for treatment or prevention of invasive SCC, they all produce a comparable reduction of approximately 75 percent in precursor actinic keratoses. However, Dr. Christensen emphasized that repeated cycles of treatment may be required because the clinical response from a single treatment tends to wane after one to two years.
Another option on the therapeutic ladder is photodynamic therapy (PDT). PDT has been shown to be superior to lesion-directed cryotherapy with liquid nitrogen, resulting in clearance of 69 to 91 percent of actinic keratoses within a treated field.
The final treatment ladder step involves systemic medications, most notably acitretin.
“The drug has proved to have a dramatic effect in decreasing the incidence of new skin cancers in patients at high risk for developing SCC,” he said. “This medicine does have significant side effects, so we have to gauge a risk profile in each individual patient. This is a medication I reserve for patients at highest risk for skin cancer development and progression. Certain patients with a very high burden of SCC will also benefit from the combination of topical and systemic therapy, coupled with surgical treatment of any persistent lesions.”