Managing high-risk squamous cell carcinoma

National report - Because there are no separate guidelines for managing high-risk squamous cell carcinoma (SCC), patients who have it need an individualized approach, according to Chrysalyne D. Schmults, M.D.

"We don't have consensus about what constitutes high-risk SCC, and therefore we don't have the numbers that accurately predict such patients' prognoses," notes Dr. Schmults, an assistant professor of dermatology in the division of dermatologic surgery at the University of Pennsylvania, Philadelphia.

Although SCC has a high cure rate, ranging from 90 percent to 95 percent, approximately 10 percent have recurrences and metastases occur in 3 percent to 5 percent of cases.

Risk factors for metastatic SCC

One landmark review from 1992 showed that certain factors were associated with a higher risk of SCC metastases, Dr. Schmults recounts. These include:

More recently another team of investigators found that in cases with metastatic SCC, 70 percent were in patients with current disease (2005). Of these, only 18 percent had SCC in situ, which is "by definition a low-risk tumor," Dr. Schmults says.

"None were treated with Mohs surgery. The majority had wide excision, and several had lymph-node dissection and radiotherapy as well."

Patients who died of SCC were more likely to have had recurrence, tumor invasion beyond the fat layer, perineural invasion and a primary tumor diameter of at least 4 cm. Integrating the findings from the two studies, Dr. Schmults notes that dermatologists should consider tumors to be high-risk if they have wide diameters, or are deep, recurrent or have perineural invasion.

However, as with many issues in medicine, the devil is in the details.

"Perineural invasion is not a well defined concept," Dr. Schmults says. "It's unclear whether invasion of a few nerve twigs in the dermis is the same as tracking along a major named nerve branch. The latter is clearly associated with poor prognosis."

She says that she and a team of investigators will be addressing this issue in particular.

Radiotherapy decisions

Several factors influence how extensively to treat a high-risk SCC, she says.

"If you can remove the lesion by Mohs surgery and are comfortable with the margins, we don't know if adjuvant radiotherapy is beneficial," she says, noting that she is reviewing the literature on this topic.

"It appears that adjuvant radiotherapy patients actually do worse, but this is likely due to selection bias, in that the worst tumors (are) referred for adjuvant treatment."

Patient factors

In addition to tumor characteristics that can increase the risk, patient characteristics can increase the risk of SCC, she says.

Patients with a compromised immune system, those with chronic lymphocytic leukemia (CLL) and those with well-differentiated small lymphocytic lymphoma (SLL) have increased risks, as do organ transplant recipients.

"The highest risk [is] in heart transplant, while the risk for renal patients is somewhat intermediate," Dr. Schmults says. "Liver transplants have the lowest risk."

Other conditions associated with poor prognosis include epidermolysis bullosa, those with exposure to arsenic, those who have undergone psoralens ultraviolet A (PUVA) as well as patients who have received radiation exposure.