Multidisciplinary treatment strategies in high-risk resectable melanoma: Role of adjuvant and neoadjuvant therapy

Abstract

Stage III melanoma encompasses a range of disease burdens, including microscopic foci of metastatic melanoma in a sentinel lymph node; bulky, clinically detected lymphadenopathy; and in-transit dermal metastases. After initial surgical management, patients with stage III melanoma at highest risk for recurrence are most likely to benefit from adjuvant therapy. Novel therapies that have improved the disease response rates and long-term survival of patients with advanced or metastatic melanoma have now been evaluated in the adjuvant setting, with the goal of eliminating residual microscopic disease to improve relapse-free and overall survival. Alternatively, implementing systemic therapies in the neoadjuvant setting for bulky, clinically detected disease can potentially limit surgical morbidity and improve understanding of an individual's response to applied therapy. With multiple therapeutic approaches currently under evaluation for adjuvant and neoadjuvant treatment of high-risk melanoma, establishing optimal treatment regimens, appropriate clinical endpoints, and treatment risk-benefit profiles has become increasingly challenging. There is also a critical need to identify and validate biomarkers predictive of melanoma patient outcomes or treatment efficacy. This article provides an overview of current clinical evidence and ongoing trials of targeted therapy and immunotherapy in this rapidly evolving area of oncology.

Neoadjuvant therapy with vemurafenib in Horner's syndrome as a very rare first diagnosis of a malignant melanoma of unknown primary

“…In about 50 % of all melanomas a BRAF mutation is detected [5,6]. The reduced risk of relapse and improvement of long-term survival have been discussed, but the individual response and tolerability before surgery still has to be evaluated [7]. The combination therapy has proven to be significantly more effective in terms of overall response rate and long-term survival [6].…”

“…Especially in the oligometastasized stage or when metastases cannot be entirely resected, neoadjuvant therapy can increase the probability of a complete metastasectomy. The reduced risk of relapse and improvement of long-term survival have been discussed, but the individual response and tolerability before surgery still has to be evaluated [7]. Previous case reports have reported the successful neoadjuvant use of vemurafenib.…”

ASO Author Reflections: Hematological Biomarkers of Survival in Cutaneous Melanoma

“…The use of adjuvant immunotherapy for resected stage III/IV disease is now commonplace. Trials of neoadjuvant immunotherapy in high-risk resectable and oligometastatic melanoma prior to resection are now underway,5 which is both interesting and concerning because immunotherapy induces serious adverse events in approximately 15% of patients receiving ipilimumab monotherapy, 2% receiving pembrolizumab, and approximately 5% receiving nivolumab. Therefore, we suggest that the selection of patients for neoadjuvant immunotherapy is of paramount importance to prevent treatment-related harm.…”

Immune Microenvironment Related Competitive Endogenous RNA Network as Powerful Predictors for Melanoma Prognosis Based on WGCNA Analysis

“…Early melanoma has a higher cure rate after complete resection, and the mortality rate of stage III/IV patients is as high as 70%, and the 5-year survival rate is less than 16% (4). In recent years, targeted therapy and immunotherapy for melanoma have made certain breakthroughs, while low response rates and severe adverse reactions have limited its long-term effects (5,6). Therefore, seeking in-depth understanding of the pathogenesis and malignant transformation mechanism of melanoma, exploring more biological targets, and making accurate prediction of the prognosis, will bring new hope for overcoming melanoma's recurrence and resistance, and improving the survival rate of patients.…”