Skin cancer recurrence may be prevented with combo of surgery, adjuvant therapies

September 1, 2010

While surgical and medical oncologists do not think twice about combining treatments such as surgery, chemotherapy and radiation therapy, in the treatment of cancer patients, dermatologists rarely use adjuvant therapies once they have excised skin cancers, according to one dermatologist.

Key Points

James M. Spencer, M.D., M.S., associate professor of clinical dermatology, Mt. Sinai School of Medicine, New York, and a practicing dermatologist in St. Petersburg, Fla., spoke at the January 2010 Orlando Dermatology Aesthetic and Clinical conference in Orlando, Fla. He argued that dermatologists tend to use only one skin cancer treatment, despite the fact that there are tried-and-true adjuvant therapies (such as radiation) and emerging medical therapies, such as imiquimod cream.

"I think this is something that we should at least think about, especially when we are concerned about recurrence after excision," Dr. Spencer says.

Squamous cell carcinoma with perineural invasion has an ominous side, according to Dr. Spencer.

"I would go ahead with the surgery, but would strongly urge readers to consider radiation therapy, postoperatively. Even with clear margins, perineural spread in squamous cell carcinoma is a bad prognosis," he says.

While he admits these are not evidence-based decisions but rather judgment calls, Dr. Spencer also says that he considers radiation therapy with particularly dangerous tumors, such as Merkel cell carcinoma.

"After surgical excision, I think that many would recommend radiation to the surgical site and, possibly, to the draining lymph nodes," he says.

"Merkel cell carcinoma is an exquisitely radiosensitive tumor," Dr. Strasswimmer says. "The other case is the situation of either poorly differentiated squamous cell carcinoma or squamous cell carcinoma with perineural invasion. The former can lead to local in-transit metastases, which are hard to detect and lead to a very poor prognosis. The latter can lead to perineural extension, with an equally dim prognosis."

However, Dr. Strasswimmer says it is not enough to simply refer a patient to a radiation oncologist postoperatively.

"Rather, the Mohs surgeon should discuss the case and help plan a reasonable field of adjunct radiation," he says.

Reasoning and evidence

Every patient wants as small a scar as possible. With this in mind, Dr. Spencer asks if it is reasonable, then, to use imiquimod cream before surgery - not to cure the cancer, but to shrink the tumor.

There are only a few studies looking at outcomes of skin cancer surgery with and without prior treatment with imiquimod, and results are mixed. Torres A et al reported in December 2004 in Dermatologic Surgery that use of 5 percent imiquimod cream prior to Mohs surgery resulted in a smaller defect than with excision only of basal cell carcinoma.

In a more recent study by Butler DF, Parekh PK and Lenis A, in the January 2009 issue of Dermatologic Surgery, researchers found no statistically significant benefit in using imiquimod 5 percent cream as an adjunctive treatment of nodular, nasal basal cell carcinomas before Mohs surgery. These researchers noted, however, that a larger study might show a benefit.

Dr. Spencer says one valid question that researchers have yet to ask is whether imiquimod use prior to Mohs might introduce skip areas. "If you introduce skip areas into the tumor, it negates histology," he says.

Despite this potential concern and limited data showing effectiveness, Dr. Spencer says it is reasonable to consider imiquimod cream use prior to surgery for the bigger, trickier skin cancers.

"Now, let us consider another scenario. You do the surgery, like you always would, but are a little nervous. Maybe you did not get it all - it was a tough cancer. Would it be reasonable to try a cream after the surgery? I cannot imagine any downside to doing that," Dr. Spencer says.

His point: Surgery is not perfect, and the cream could be a patient's insurance policy against recurrence.

"Lentigo maligna, or melanoma in situ, has a local recurrence rate of 10 percent to 20 percent, according to the literature. That is significant," Dr. Spencer says. "Imiquimod has been studied as an effective monotherapy for lentigo maligna. So, in my practice, I excise lentigo maligna and follow that with topical imiquimod. Do I have proof that is helping anybody? No. But I would argue that falls into the 'Why not?' category."

Treatment possibilities

Some might also apply this thinking to certain basal cell skin cancers, known to recur more because of their size or location.

"The worst that could happen is nothing; the best that could happen is that your recurrence rate would go down," Dr. Spencer says.

Imiquimod is clearly proven in its ability to treat thin basal cell carcinoma and squamous cell carcinoma in situ, making it a good idea in these cases, according to Dr. Strasswimmer.

"In contrast, treatment preoperatively is fraught with potential for problems. First, the duration of treatments required places the patients at a two-month delay in treatment. Add in the needs time for the inflammation to quiet down, and there is a real potential for clinically important delay," Dr. Strasswimmer says.

There are certain cases in which post-operative treatment with imiquimod is not only a good idea - it might soon become standard treatment, according to Dr. Strasswimmer.

"As the link grows between oncogenic human papillomavirus (HPV) infection and squamous cell carcinoma tumors of certain locations, imiquimod offers a 'double whammy' to clear up other small subclinical squamous cell lesions and addresses this important viral etiologic factor at the same time. Periungual and genital squamous cell carcinoma are two such examples," he says.

Disclosures: Dr. Spencer is an investigator for Graceway Pharmaceuticals. Dr. Strasswimmer is a consultant to Nucletron BV and Graceway Pharmaceuticals.