SCC staging update defines high-risk tumors

New York - A new tumor staging system for cutaneous squamous cell carcinoma (CSCC) has recently been put forward that, according to one recent study, improves prognostic discrimination by more precisely defining the small subset of tumors with a high risk of metastatic and death.

The tumor staging protocol put forth by the American Joint Committee on Cancer (AJCC) is the most widely accepted staging system used by U.S. physicians. In contrast to earlier AJCC staging systems that defined a greater than 2 cm tumor diameter as the only parameter that differentiated a patient from having T1 or T2 tumor stage, the newly revised AJCC staging system put forth in 2010 now includes additional risk factors, which essentially broadened the number of tumors that could be classified as T2 tumor stage.

“Appropriately defining the parameters for high-risk CSCC is instrumental in accurately defining risk. A staging system is supposed to be able to tell you which tumors are higher risk because they should have a higher tumor stage. Our study was the first to evaluate AJCC staging with actual patient data,” says Chrysalyne D. Schmults, M.D., assistant professor of dermatology, Harvard Medical School, Director, Brigham and Women’s Mohs and Dermatologic Surgery Center, Boston.

Testing the staging system

A staging system should ideally be designed to have more poor outcomes occurring at higher stages, Dr. Schmults says, so that patients with low stage disease should have a relatively low risk of having a poor outcome, and as one progressively moves towards higher and higher tumor stages, the risk of having a poor outcome (i.e. recurrence, metastasis or death) should increase with a higher tumor stage.

Dr. Schmults and colleagues recently conducted a study to test this premise, and validate the current AJCC staging system in a group of patients with CSCC (Jambusaria-Pahlajani A, Kanetsky PA, Karia PS, et al. JAMA Dermatol. 2013;149(4):402-410). The study design was aimed at quantifying how many patients were in each AJCC tumor stage, how outcomes varied across stages, and determine if any improvements could be made in staging criteria.

The single-center, retrospective cohort study included 256 CSCCs. Outcomes of nodal metastasis and death for AJCC tumor stages T2 to T4 were statistically indistinguishable because only four cases were AJCC stage T3 or T4, which require bone metastasis. Data showed that the bulk of poor outcomes including 83 percent of nodal metastasis and 92 percent of deaths occurred in AJCC stage T2.

Dr. Schmults and her colleagues then devised an alternative tumor staging system with the aim of better stratifying this stage T2 group into a high-risk and low-risk group. They found that four risk factors were statistically independent prognostic factors for at least two poor outcomes in multivariate modeling: poor differentiation, perineural invasion, a tumor diameter equal to or greater than 2 cm, and invasion beyond the subcutaneous fat.

These four risk factors were then incorporated in the alternative staging system with zero factors indicating T1, one factor indicating T2a, two to three factors for T2b, and four factors or bone metastasis for T3. The alternative staging system results showed that stages T2a and T2b significantly differed in incidences of poor outcomes. While stage T2b tumors comprised only 19 percent of the cohort, they accounted for 72 percent of nodal metastases and 83 percent of deaths resulting from CSCC.

Identifying high-risk patients

One of the central goals of this alternative staging system is to be able to better identify patients at risk for poor outcomes, and quantify the risk of lymph node metastases that may lead to death from SCC. A more accurate staging system can lead to more targeted treatments in those patients with a high risk of metastasis, Dr. Schmults says, and more aggressive treatment of high-risk patients will hopefully improve outcomes in this high-risk group, and ensure that low-risk patients are not over-treated.

“The vast majority of patients with CSCC do very well just with complete surgical excision. What we need to do is figure out which patients have a substantial risk of recurrence after a clear-margin surgery, because then we will know which patients need nodal staging or might benefit from adjuvant radiation and/or chemotherapy,” Dr. Schmults says.

According to Dr. Schmults, many clinicians today are torn regarding which patients need adjuvant treatment or nodal staging, as there is currently no clear-cut consensus regarding which patients need more than surgery.

“Different practitioners are doing different things in terms of when and in whom to move forward with nodal staging and adjuvant radiation,” she says. “This lack of certainty indicates that we are in dire need of better data to help guide us in managing our high-risk SCC patients better. Our proposed alternative staging system can hopefully be a first step in defining a high-risk group for further clinical trials of staging and adjuvant treatment,” Dr. Schmults says.

Disclosures: Dr. Schmults reports no relevant financial interests.