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Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer. While most cases are curable, some can spread to other parts of the body, becoming life-threatening. Currently, physicians use physical features of the tumor to predict which cases might spread, but this method is not always accurate. A new test called gene expression profiling (GEP) looks at the activity of certain genes in the tumor to better predict which cases are high-risk. This review examines a specific 40-gene test for cSCC, evaluating how it works and reporting accuracy in predicting metastasis and potential impacts on patient care. We found that GEP can improve risk prediction when used alongside current methods. This could help doctors make better decisions about treatment and follow-up care, potentially improving outcomes for patients with cSCC. Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, with an increasing global incidence. While most cases are successfully treated with surgical excision, a subset can metastasize, leading to significant morbidity and mortality. Current staging systems based on clinical and histopathological features have shown limitations in accurately predicting metastatic risk. This review examines the role of gene expression profiling (GEP), particularly the 40-gene expression profile (40-GEP) test, in improving risk stratification and management of cSCC. We assess the prognostic value of the 40-GEP test, its integration with current staging systems, and its impact on clinical decision-making. Recent studies suggest that incorporating GEP results with traditional staging methods can enhance the identification of high-risk patients, potentially leading to more personalized treatment strategies. The review also explores the challenges of implementing GEP in routine clinical practice, including cost-effectiveness considerations and the need for standardization. Finally, we discuss the implications for future cSCC management and highlight areas for further research. As molecular profiling techniques continue to evolve, GEP represents a promising approach to optimizing care for cSCC patients, aligning with the growing emphasis on personalized medicine in oncology. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous melanoma is a malignancy of melanocytes with increasing global incidence. While most early-stage cases have favorable outcomes, melanomas can unexpectedly progress, highlighting the need for better risk prediction methods. This review examined the 31-gene expression profile (31-GEP) test, which analyzes the activity of 31 genes in melanoma tumors to predict the risk of metastasis. Data from multiple studies was systematically reviewed and analyzed to assess the 31-GEP test's efficacy in predicting melanoma patient outcomes. Our findings suggest that the 31-GEP test may improve risk prediction when used alongside standard clinical and pathological assessments. By using 31-GEP, physicians may be better able to make more informed decisions about treatment and follow-up care, potentially improving outcomes for melanoma patients. Background: Cutaneous melanoma is an increasingly common and potentially lethal form of skin cancer. Current staging systems based on clinical and pathological features have limitations in accurately predicting outcomes, particularly for early-stage disease. The 31-gene expression profile (31-GEP) test has emerged as a promising tool for improving risk stratification in melanoma patients. Methods: We conducted a systematic review and meta-analysis of studies evaluating the prognostic performance of the 31-GEP test in cutaneous melanoma. A comprehensive literature search was performed in multiple databases. Studies reporting survival outcomes stratified by 31-GEP class were included. Random-effects models were used to determine survival estimates across studies. Results: Thirteen studies comprising 14,760 patients were included in the meta-analysis. The 31-GEP test consistently stratified patients into risk groups with significantly different outcomes. The 5-year melanoma-specific survival rates were 99.8% (95% CI: 98–100%) for Class 1A, 97.6% (95% CI: 92.4–99.3%) for Class 1B/2A, and 83.4% (95% CI: 66.5–92.7%) for Class 2B. Similar trends were observed for recurrence-free and distant metastasis-free survival. Conclusions: This meta-analysis supports the prognostic utility of the 31-GEP test in cutaneous melanoma prognostication. The test consistently stratified patients into clinically meaningful risk groups across multiple survival metrics. These findings support the potential clinical utility of the 31-GEP test in enhancing current staging systems and informing personalized management strategies for melanoma patients. [ABSTRACT FROM AUTHOR]