What Defines High-Risk SCC Is Not Always Clear-Cut

CORONADO, Calif. — Despite recent advances in the treatment of cutaneous squamous cell carcinoma (SCC), a lack of consensus remains on what defines high-risk disease, according to Travis W. Blalock, MD, MBA.

“There’s a lot of variability in regard to what we believe to be higher-risk tumors,” Blalock, director of Dermatologic Surgery, Mohs Micrographic Surgery, and Cutaneous Oncology at Emory University School of Medicine, Atlanta, said at the annual Melanoma and Cutaneous Oncology Symposium. “So as we convey these risks to patients or we make decisions based on our perceptions, the reality is we’re not quite unified.”

Clinicians often discuss with their patients the risk for local recurrence, metastatic disease, and disease-specific death using existing staging classification tools, he continued. However, these risk factors do not always align perfectly. “For example, if you look at diameter of the SCC lesion, which has been the quintessential tumor-specific factor that we’ve considered, that has a strong correlation with disease-specific death, which should not be surprising to us,” he said. “That doesn’t mean that some of the other factors aren’t important.”

In a 2023 study, French researchers compared the performance of the Brigham and Women’s Hospital (BWH) classification with the performances of the American Joint Committee on Cancer Eighth Edition (AJCC8), the Union for International Cancer Control Eighth Edition (UICC8), and the National Comprehensive Cancer Network (NCCN) classifications in classifying 217 head and neck cutaneous SCCs from 160 patients (mean age, 80 years). The investigators found that to predict poor outcomes, with local recurrence, lymph node recurrence, and disease-specific death combined as a single risk, the BWH classification had significantly lower sensitivity than the AJCC8, UICC8, and NCCN classifications (P = .01, P = .05, and P = .001, respectively) but better specificity (P

However, its concordance index was not significantly higher than indices of the AJCC8 and UICC8 classifications. The NCCN classification was the least discriminant. Blalock, who was not involved with analysis, noted that the NCCN guidelines classified about 210 (of the 217 tumors) as high risk. “If we’re classifying 97% of squamous cell carcinomas automatically as high-risk tumors, how are we able to discriminate for these patients?”

Going forward, Blalock called for a “middle ground” approach to predict the risk for poor outcomes in patients with cutaneous SCC. “What is the happy medium?” he asked at the meeting, which was hosted by the Scripps Cancer Center, San Diego. “You probably don’t want to include everybody as high risk, but we don’t want to be so specific that we can’t pick up [outliers]. There are other factors to consider integrating into these high-risk categories.”

Blalock discussed additional variables that could affect patient outcomes and should be considered in staging systems, such as the patient’s age or other histopathologic findings. He said that while “high risk” may seem like a simple, binary concept, “we’re not quite there yet for SCC — not for us, not for the patient, and not for researchers.”

Blalock reported having no financial disclosures.