By Diane Donofrio Angelucci, contributing writer, May 01, 2013
Non-melanoma skin cancer accounts for the largest proportion of cancer cases of any kind in the United States, and its incidence continues to rise.
As the number of cases grows, however, research is advancing knowledge of the epidemiology and treatment of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), providing clinicians with powerful tools to help them hone their prevention and medical treatment strategies.
Understanding SCC risks
Researchers now know much more about the epidemiology of SCC in the U.S., identifying populations most prone to the disease and high-risk cases, said Abrar Qureshi, MD, MPH, vice chairman and co-director of the Center for Skin and Related Musculoskeletal Diseases at Brigham and Women’s Hospital, and Harvard Medical School. This is critical knowledge. “It turns out that SCC is responsible for a large number of deaths in the U.S., almost equaling those occurring from melanoma, which is a largely unknown fact,” Dr. Qureshi said.
“Dermatologists need to know the risk factors for SCC so they can advise their patients better both in terms of their protection as well as self-exams and to come in earlier when the skin cancer initially arises,” Dr. Qureshi said. “SCC is one of those skin cancers that arises quickly, much more acutely than BCC, and earlier diagnosis would help minimize surgery and treatment.” Furthermore, early treatment reduces the risk of metastasis, he said. [pagebreak]
Sun exposure is a known risk factor for BCC and SCC, and photosensitizing medications may boost this threat, said Craig A. Elmets, MD, professor and chair of the department of dermatology and director of the University of Alabama at Birmingham Skin Diseases Research Center. For example, in an article recently accepted for publication, Robinson and colleagues reported in the Journal of Investigative Dermatology (doi: 10.1038/jid.2013.33) that photosensitizing medications may increase the risk of BCC and, particularly in those who reported a tendency to sunburn, of SCC.
Furthermore, immunocompromised patients, such as those with HIV or diabetes and organ transplant recipients, also are known to be at increased risk of SCC, said Gary Goldenberg, MD, assistant professor of dermatology and pathology at New York’s Mount Sinai School of Medicine and medical director of the medical center’s dermatology faculty practice.
To reduce risks in patients scheduled to receive transplants, dermatologists must screen them thoroughly for warts, actinic keratoses, and early squamous lesions and treat them before surgery, he explained.
A partnership between the dermatologist and transplant physician is also key. “The role of the dermatologist in the care of the transplant patient is not just in the detection and prevention of skin cancers, but to communicate with the transplant physicians which of the medicines is less likely to cause SCC and to help improve that patient’s quality of life,” said Christopher J. Miller, MD, director of dermatologic surgery at the University of Pennsylvania. [pagebreak]
Although immunosuppressive medications increase the risk of skin cancer, by decreasing and adjusting their immunosuppression clinicians can decrease the volume of skin cancer, Dr. Goldenberg said. “For example, cyclosporine is one of the biggest offenders when it comes to making skin cancers,” he said. “Putting someone on rapamycin decreases that risk by quite a bit; that has been shown in several studies.” A study by Euvrard and colleagues in the New England Journal of Medicine (2012; 367:329-339) showed that switching kidney transplant recipients who had had at least one skin cancer from calcineurin inhibitors to sirolimus reduced the risk of skin cancer.
In addition, Dr. Goldenberg explained that multiple studies have shown that acitretin decreases the incidence of SCC in patients who have received transplants; however, he added, it appears this effect persists only while the patient is taking the drug.
Systemic options may also help prevent SCC and BCC. Dr. Elmets and his colleagues reported in the Journal of the National Cancer Institute in 2010 (102(24): 1835-1844) that celecoxib reduced the risk of non-melanoma skin cancer in those with many AKs and those who were at increased risk for non-melanoma skin cancer. “Celecoxib has cardiovascular effects, but there are other nonsteroidal anti-inflammatory drugs that show promise and could potentially be employed as preventive agents for these types of malignancies,” he said. [pagebreak]
Identification of high-risk lesions is also essential in preventing SCC metastases. “It’s important for clinicians to know about the risk factors for high-risk lesions because patients need to be monitored. For example, lymph node exams need to be performed in people who get head and neck SCC that is of a certain histologic type or of a certain depth or size because those tumors are much more amenable to metastasis,” Dr. Qureshi said.
The American Joint Commission on Cancer (AJCC) developed a new staging system in 2011 based on tumor characteristics, segregating SCCs from other non-melanoma skin cancers and indicating high-risk characteristics. “That’s important because if we have uniform documentation of the stage of the SCCs that we treat, and if pathologists routinely recorded the presence or absence of those high-risk characteristics on their pathology reports, then suddenly we have a very powerful way of collecting data on a large group of skin cancers that is currently not segregated,” Dr. Miller said.
“There are studies to show if an SCC is more than a couple of millimeters in depth, it does have a higher chance of metastasizing, especially if it’s more than 6 mm, which is a pretty deep squamous cell,” Dr. Goldenberg said. Brantsch and colleagues reported on this in 2008 in The Lancet Oncology (9(8):713-720). [pagebreak]
Perineural invasion is also an important indicator. “We know that squamous cells like to wrap around those nerves and they kind of track down the nerves,” he said. As a result, they may spread to another area of the skin. Furthermore, SCC is more aggressive in specific locations, such as the lips and ears, Dr. Goldenberg said.
Researchers increasingly are learning more about the epidemiology of BCC, which is associated with risk factors such as sun exposure, smoking, and obesity.
Vismodegib, which was approved in 2012 to treat metastatic BCC, advanced BCC that recurred after surgery, or patients who cannot be treated with surgery or radiation, is transforming treatment strategies by filling a previous void.
Although surgery is the mainstay in treating BCC (see article), this option may be difficult or impossible in patients with inoperable BCC, metastatic BCC, or patients with numerous BCCs, Dr. Miller said. “Vismodegib is a new systemic option to treat these inoperable or metastatic BCCs,” he said. [pagebreak]
Furthermore, vismodegib, which targets the molecular pathway of BCC, was used for operable BCCs, as reported by Gross and colleagues at the 2012 meeting of the Society of Investigative Dermatology (abstract 543). The study treated patients with vismodegib who had BCCs of approximately 1 cm, which normally would be excised or removed via Mohs surgery. “They had good response rates and patients tolerated the drug fairly well,” Dr. Goldenberg said.
Dr. Goldenberg explained that research needs to examine the use of vismodegib in shrinking BCCs in cosmetically sensitive areas and surgically removing the remaining tumor.
In preventing skin cancer, patient education regarding sunscreen use and sun protection remains critical. “Things of that nature are just vitally important, and unless we do a better job of encouraging sun protection the incidence of skin cancers is going to continue to increase,” Dr. Goldenberg said. [pagebreak]
Researchers are examining epidermal growth factor receptor inhibitors in SCC. “There are case reports showing some response in patients with cutaneous SCCs but no large studies,” Dr. Miller said.
Ongoing advancements will emerge to treat BCC and SCC. “There are a lot of developments on the horizon that are really based on basic research that’s been done over the past several years in the pathogenesis of skin cancer showing that the development of skin cancers proceeds through an orderly sequence of events in which molecular or biochemical changes occur,” Dr. Elmets said. “By targeting these various pathways and the mutations that are associated with them, a number of new drugs are being identified, which in the future may help to reduce the growing epidemic of non-melanoma skin cancer.”
Editor’s note: Dr. Goldenberg has served as a consultant for and received honoraria from Genentech, Graceway, Medicis, and LEO Pharma; he also has been an investigator for Graceway, Medicis, LEO Pharma, and PharmaDerm. Dr. Elmets has served as a consultant for Genentech. Dr. Miller and Dr. Qureshi have no financial interests related to their comments.