A RECENT study has revealed a clear pattern: as the number of risk factors in cutaneous squamous cell carcinoma (CSCC) increases, so does the likelihood of recurrence, metastasis, and disease-specific mortality. Rather than viewing each risk factor in isolation, the study highlights the cumulative impact of multiple risk factors, revealing a striking pattern of escalating risk with each additional factor.
One of the most compelling takeaways is the exponential nature of risk escalation. Patients with no risk factors exhibited low incidences of adverse outcomes, whereas those with even a single risk factor saw a notable increase in recurrence and metastatic potential. This trend intensified dramatically as the number of risk factors increased, with the most substantial jumps occurring between two and three risk factors. Notably, those with four risk factors faced markedly heightened risks, with over a third experiencing local recurrence and a quarter succumbing to disease-related mortality.
These results have significant clinical implications, particularly for risk stratification and treatment planning. Current staging systems, such as the Brigham and Women’s Hospital (BWH) classification, group certain CSCCs together despite variations in their number of risk factors. The findings suggest that this approach may overlook important distinctions between risk subsets. For example, within the BWH T2b classification, tumours with three risk factors demonstrated substantially higher recurrence and metastasis rates compared to those with two, suggesting that additional refinement of staging criteria could be beneficial in clinical decision-making.
From a therapeutic perspective, these findings advocate for a more tailored approach to treatment. Patients with higher numbers of risk factors may warrant more aggressive interventions, such as closer surveillance, earlier consideration of adjuvant therapies, or more extensive surgical excision. Conversely, those with fewer or no risk factors might avoid overtreatment, minimising unnecessary interventions and associated morbidities.
Ultimately, this study reinforces the importance of a nuanced approach to CSCC prognosis and management. By recognising the cumulative effect of risk factors, clinicians can better predict patient outcomes and refine treatment strategies accordingly, leading to improved patient care and resource allocation. The results highlight the need for ongoing research into personalised CSCC treatment protocols to further enhance patient outcomes.
Reference
Ran NA et al. Risk factor number and recurrence, metastasis, and disease-related death in cutaneous squamous cell carcinoma. JAMA Dermatol. 2025;DOI:10.1001/jamadermatol.2025.0128.
