Study Supports Updates to Staging Systems for Cutaneous Squamous Cell Carcinoma

A multi-institutional research effort led by Shlomo Koyfman, MD, Department of Radiation Oncology, Cleveland Clinic has demonstrated that cutaneous squamous cell carcinoma (CSCC) patients with satellitosis or in-transit metastasis (S-ITM) have similar outcomes to individuals with node-positive disease.

The study authors also observed an increased risk of recurrence and worse survival among this patient population when compared with T3 and T4 disease. These findings, which were published in JAMA Dermatology, identify S-ITM as an important prognostic factor that should be incorporated into clinical staging systems (2022;158(4):390-4).

Cutaneous squamous cell carcinoma is one of the most common skin cancers in the U.S., according to Dr. Koyfman, who notes that while the majority of cases are stage one and have an excellent prognosis, a subset of patients present with more advanced disease. Having the appropriate staging systems in place is important to help clinicians risk-stratify these patients and determine the appropriate treatment.

“S-ITM, or the presence of dermal lesions between the primary tumor and first-echelon lymphatic nodal basins, is a rare yet significant risk factor for cutaneous squamous cell carcinoma,” Dr. Koyfman explains. “However, S-ITM is not currently included in the AJCC Cancer Staging Manual, 8th edition (AJCC-8) and the Brigham and Women’s Hospital (BWH) staging systems.”

And so, determining the right treatment approach for patients with CSCC and satellitosis or in-transit metastasis can prove challenging. Dr. Koyfman and his colleagues set out to evaluate the connection between S-ITM and clinical outcomes in cutaneous squamous cell carcinoma patients as well as to better understand its prognostic value.

Methods & findings

A dual-institution database—Cleveland Clinic and Brigham and Women’s Hospital— was used to identify patients who received treatment for cutaneous squamous cell carcinoma between 2010 and 2020. These patients were node-negative and had satellitosis or in-transit metastasis.

The research team used subcohorts of patients with T3N0 tumors, T4N0 tumors (bone invasive), N1 to 3 and M1 disease for comparison. Cancer stages were defined based on the American Joint Committee on Cancer staging system.

Among 518 CSCC patients, satellitosis or in-transit metastasis was present in 72 (13.9 %) patients who were node-negative. They had a median age of 73.9 years. 82 percent were men, and 96 percent were White, non-Hispanic. Thirty-five percent of these individuals had immunosuppression. In the subcohorts, 341 patients had T3N0 cancer, 36 had T4N0, 70 had N1 to 3 and 19 had M1 disease.

Dr. Koyfman and his colleagues observed a lower cumulative incidence of CSCC recurrence rates in the T3N0 and T4N0 groups when compared with the S-ITM cohort. Additionally, the data showed no significance difference between node-positive patients and those with S-ITM.

The five-year disease-specific survival rates for T3N0, T4N0, S-ITM and N1 to 3 were 76 percent, 64 percent, 41 percent and 39 percent, respectively.

When compared with the S-ITM patient group, the study authors reported significantly higher disease-specific survival among T3N0 and T4N0 patients. However, it was not significantly different in the node-positive and metastatic cohorts.

Clinical significance

Based on their findings, the research team argues that S-ITM should be codified in cutaneous squamous cell carcinoma staging systems, similar to what has been done in Merkel cell carcinoma and melanoma. They are actively lobbying to adjust the staging systems to reflect the prognostic value of satellitosis or in-transit metastasis in CSCC.

Dr. Koyfman, who is involved in a number of national and international research studies, is also working with his colleagues to ensure CSCC patients with S-ITM are eligible for inclusion in high-risk clinical trials, such as KEYNOTE-630 which is exploring adjuvant pembrolizumab in high-risk locally advanced cutaneous squamous cell carcinoma (NCT03833167).

“Our work has significant implications for both research and clinical practice,” notes Dr. Koyfman. “This patient population, while at a relatively high risk for recurrence and death from skin cancer, is still curable. These findings can help inform clinical decision-making, particularly in the adjuvant setting.

When a patient presents with satellitosis or in-transit metastasis, don’t hesitate to reach out to your colleagues for support,” he says. “We have a Tumor Board that was started ten years ago to help us navigate the treatment of patients with advanced skin cancers. These are complicated cases that require a multidisciplinary approach.”

Dr. Koyfman and the multidisciplinary team will often choose primary immunotherapy as an initial management for these patients. “We have seen some of these patients be treated with immunotherapy alone and have complete response of their cancer that lasts for years. Immunotherapy should be considered as a primary therapy for some of these patients.”