The prognostic value of regression change in melanoma

Background: Regression in melanoma refers to an immune-mediated partial or whole vanishing of various tumor cells. It is important to note that regression is a common histopathological finding, but its prognostic significance is very controversial. This meta-analysis aims at evaluating the prognostic value of regression in cutaneous melanoma patients. Methods: A literature search will be undertaken across various electronic databases. The databases include PubMed, Embase, Web of Science, and Cochrane Library for studies published up to October 2024. Notably, it will include studies that investigated the existing relationship between histological regression and patient outcomes in melanoma. Studies reporting various hazard ratios (HRs) and sufficient data to calculate risk estimates for survival outcomes will be included. Various random-effects models will be applied in calculating pooled effect estimates. Results: Ten studies involving 3,782 melanoma patients attained the inclusion criteria. The presence of regression was not significantly related to overall survival (OS) (HR is equal to 0.87, 95% CI: 0.69-1.10, p = 0.24). The regression revealed a significant association with improved disease-free survival (DFS) (HR is equal to 0.72, 95% CI: 0.58-0.89, p is equal to 0.003). Subgroup analysis revealed that extensive regression (is more than 50% of tumor area) was related to better prognosis (HR is equal to 0. 65, 95% CI: 0.48 - 0.88, p is equal to 0.006) compared to partial regression. Regression in thin melanomas (is less than or equal to 1 mm) revealed a more substantial protective effect (HR is equal to 0.61, 95% CI: 0.45 - 0.83, p is equal to 0.002) than in thick melanomas. Conclusions: The meta-analysis suggests that regression in melanoma, especially extensive regression in thin melanomas, is related to improved disease-free survival. Therefore, the findings challenge the traditional view that regression represents a negative prognostic factor. It also challenges the suggestion that the extent of regression and tumor thickness are important considerations when evaluating its prognostic impact. Further prospective studies with standardized regression assessment criteria are essential in validating the findings.