Understanding what defines a patient as being at high risk for developing a recurrence or metastasis from squamous cell carcinoma is important for optimally managing these patients. One expert reviews the clinical characteristics and current treatments of high-risk SCC patients.
Philadelphia - Though the cure rate of cutaneous squamous cell carcinoma (SCC) is 90 to 95 percent, overall, approximately 10 percent of these cancers do recur and a subset (up to 5 percent in some reports) of them do metastasize.
According to one specialist, the ability to better define those patients who are at high risk for developing recurrent or metastatic SCC can lead to better management and thereby a possible prevention of metastasis, ultimately leading to better prognoses.
Defining high-risk patients
"A squamous cell carcinoma with a poorly differentiated, acantholytic or infiltrative histology may also have a higher chance of metastasizing. Also, those patients who are immunocompromised are at a higher risk of developing metastasis," says Chrysalyne D. Schmults, M.D., assistant professor of dermatology and director of research of the division of dermatologic surgery at the University of Pennsylvania, Philadelphia.
Examining risk factors
Accurate prognostic models do not yet exist for cutaneous SCC.
Most high-risk tumors have more than one risk factor present, and it is difficult to estimate a particular patient's prognosis from the available literature. A recent study by Mullen, et al. (Ann Surg Oncol. 2006;13:902-909), showed that poor differentiation, diameter greater than 2 cm and occurrence within scar are significantly associated with death on univariate analysis with hazard ratios of 2.92, 3.79 and 3.12, respectively. Dr. Schmults says that for hazard ratios less than these, further studies involving more patients would need to be done.
Regarding whether a hazard ratio less than three has any clinical importance, Dr. Schmults says, "It depends on the baseline risk. A hazard ratio of three means there's a threefold increase in the risk as compared to whoever was used as the comparison group in the study. An increase in risk of metastasis from 2 to 5 percent is different than an increase of 10 to 30 percent."
Dr. Schmults notes that in the study cited above, multivariate analysis (which accounts for overlap and interaction of effect of different risk factors and isolates each risk factor individually) showed only nodal disease to be a significant risk factor for death, with a hazard ratio of 7.64. She says that the results indicated that the study was not sufficiently powered to find a hazard ratio less then 7.6, but that lesser risks are likely very important clinically.
A larger study is needed to accurately determine the risks of recurrence, metastasis and death associated with individual risk factors adjusting for overlap and interaction between factors.
Considering other factors
Patient or host factors, as well as tumor factors, may play a role in the outcome of SCC.
Results of one study on SCC in immunosuppressed patients showed a 13 percent metastasis rate in 417 patients considered immunosuppressed.
"HIV is not definitively associated with high-risk squamous cell carcinoma. Yet, the increased incidence of anal and penile SCC is usually associated with HPV," Dr. Schmults says.
She says that up to one-third of patients with chronic lymphocytic leukemia or small or well-differentiated lymphocytic lymphoma develop other malignancies, of which the most common is squamous cell carcinoma. These SCCs are often aggressive and multiple and have a mortality as high as 40 percent in chronic lymphocytic lymphoma patients.
According to Dr. Schmults, organ transplant recipients have a 65-fold increased risk of SCC. The incidence appears to correlate with the intensity of the immunosuppression, and the course can be aggressive.
She says that SCC is a common cause of death in heart transplant patients, and cites one study that showed that 4 percent of heart transplant patients developed an aggressive cutaneous SCC within 10 years of transplant. Sixty-seven percent of these patients had died from SCC or were suffering from distant metastasis when the study was published.