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In-transit metastasis may be overlooked as an important risk factor in cSCC staging


Patients with S-ITM had a similar 5-year disease-specific survival (DSS) as those with positive lymph nodes (HR 0.77, 95%CI 0.84-3.93, p=.3) or distant metastasis (HR 1.81, 95%CI 0.84-3.93, p=.13) and worse than patients with T3N0 (HR 0.23, 95%CI 0.15-0.35, p=<.001) or T4N0 (HR 0.37, 95%CI 0.19-0.76, p=.01) disease.

Clinical Pearls

  • This was a retrospective, dual-institution cohort database study of patients with cutaneous squamous cell carcinoma (cSCC) treated between 2010-2020 comparing outcomes of similarly staged patients with and without satellitosis/in-transit metastases (S-ITM)

  • 72/518 patients with cSCC had S-ITM. Pairwise comparison stratified by American Joint Committee on Cancer 8th Edition (AJCC8) using Cox proportional hazard ratio (HR) showed patients with S-ITM had a similar 5-year disease-specific survival (DSS) as those with positive lymph nodes (HR 0.77, 95%CI 0.84-3.93, p= .3) or distant metastasis (HR 1.81, 95%CI 0.84-3.93, p= .13) and worse than patients with T3N0 (HR 0.23, 95%CI 0.15-0.35, p<.001) or T4N0 (HR 0.37, 95%CI 0.19-0.76, p=.01) disease.

  • Patients with S-ITM also had similar 2-year recurrence rates as patients with positive lymph nodes and distant metastasis (and worse than T3/4N0 disease).


Discussion:

Cutaneous squamous cell carcinoma (cSCC) affects upwards of 1 million patients a year in the United States alone. Despite improved public awareness regarding sun safety and improved clinicohistopathologic tools to catch disease earlier, aggressive variants of cSCC exist and can lead to increased morbidity and mortality. Several staging systems have been developed to risk stratify cSCCs, namely the American Joint Committee on Cancer 8th edition (AJCC) and the Brigham and Women’s staging system (BWH). While these systems account for a large variety of risk factors, they do not currently account for satellitosis/in-transit metastases (S-ITM).


The authors performed a retrospective, dual-institution cohort database study of patients with cSCC treated between 2010-2020, comparing outcomes of similarly staged patients with and without S-ITM. Among 518 patients treated for cSCC between 2010-2020, 72 were noted to have S-ITM (median age 73.9). Cox proportional hazard ratio found that patients with S-ITM had worse 2-year recurrence rates than T3N0 (HR 0.21, 95%CI 0.14-0.30, p<.001), T4N0 (HR 0.36, 95%CI 0.19-0.68, p=.001) and were not significantly different from node-positive patients (HR 0.74, 95%CI 0.48-1.14, p=.16).


S-ITM also had significantly worse 5-year disease-specific survival than T3N0 (HR 0.23, 95%CI 0.15-0.35, p<.001) or T4N0 (HR 0.37, 95%CI 0.19-0.76, p=.01) disease and were not significantly different from node-positive patients (HR 0.77, 95%CI 0.84-3.93, p= .3) or those with distant metastasis (HR 1.81, 95%CI 0.84-3.93, p= .13)


Limitations of this study include its retrospective design and failure to account for treatment variation as well as limited sample size.


The authors note the importance of S-ITM in other cutaneous malignancies (e.g., Merkel cell carcinoma (MCC) and cutaneous melanoma (CM)) but note that currently equivalent clinical findings do not translate to cSCC management. Findings that S-ITM carry similar disease-specific survival as regional nodal or even distant metastases may suggest that there are cSCC variants with aggressive biological adaptations and may be an area of future investigation for prognosis and management.

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