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These studies suggest that cutaneous squamous cell carcinoma (cSCC) is a common and complex skin cancer with high recurrence and mortality rates, requiring proper identification, management, and new systemic therapies like immunotherapy for improved outcomes.
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Cutaneous squamous cell carcinoma (cSCC) is a prevalent form of non-melanoma skin cancer, representing 20% to 50% of all skin cancers . The incidence of cSCC is on the rise, particularly among individuals with fair skin, advanced age, and those with a history of prolonged sun exposure or immunosuppression. Other significant risk factors include previous skin cancer diagnoses and cumulative sun exposure.
cSCC can develop de novo or progress from actinic keratosis (AK), an in situ carcinoma. The progression from AK to invasive squamous cell carcinoma (iSCC) involves a multistage process characterized by genetic mutations, epigenetic modifications, viral infections, and changes in the microenvironment . Notably, AK with atypical basal cells (AK I) is frequently associated with the development of invasive SCC.
Accurate diagnosis of cSCC is crucial for effective management. Techniques such as dermoscopy and reflectance confocal microscopy have enhanced diagnostic accuracy. The American Joint Committee on Cancer (AJCC) has updated its staging guidelines to better reflect high-risk clinicopathologic features, aiding in the stratification of patients into high- and low-risk groups . These staging systems are essential for guiding treatment decisions and predicting outcomes .
Surgical excision remains the first-line treatment for most cSCC cases, offering high cure rates . Mohs micrographic surgery is particularly effective, as it spares the maximal amount of healthy tissue while ensuring complete tumor removal. For patients who are not candidates for surgery, radiotherapy is a viable alternative. Other treatment modalities include electrodessication and curettage, cryosurgery, topical medications, photodynamic therapy, and systemic therapies.
A subset of cSCC cases is associated with a higher likelihood of recurrence, metastasis, and mortality . For these high-risk tumors, additional treatments such as immunotherapy with immune checkpoint inhibitors (e.g., Cemiplimab) and epidermal growth factor receptor inhibitors have shown promise. Despite these advancements, there is a need for more randomized controlled trials to compare the efficacy of different interventions for primary non-metastatic cSCC.
Cutaneous squamous cell carcinoma is a common and increasingly prevalent skin cancer with significant potential for recurrence and metastasis. Early diagnosis, accurate staging, and appropriate treatment are critical for effective management. While surgical excision remains the cornerstone of treatment, emerging therapies offer hope for patients with advanced or high-risk cSCC. Continued research and well-designed clinical trials are essential to improve the evidence base and optimize patient outcomes.
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