Role of Isolated Limb Perfusion in the Era of Targeted Therapies and Immunotherapy in Melanoma. A Systematic Review of The Literature

SIMPLE SUMMARY: Melanoma still represents a major challenge for health systems around the world. A classical treatment for patients with a high tumor burden or rapidly recurrent in-transit metastases is isolated limb perfusion (ILP) therapy instead of locoregional surgical resection, or when the latter is no longer feasible. In this era of modern systemic treatments for melanoma, it still remains interesting to analyze the role of management approaches for locoregionally-advanced disease, such as isolated limb perfusion (ILP). With this purpose, we conducted a systematic review updating the available literature on ILP for malignant melanomas. The main objectives of this review were to focus on the effectiveness and safety of ILP. In conclusion, ILP, with its low incidence of regional and systemic toxicity, is a valuable palliative treatment not only for patients with disease confined to a limb, but also for patients with a metastatic melanoma with a bulky or symptomatic disease, in order to improve their quality of life. ABSTRACT: Background. Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP. Methods. PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000–2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures. Results. Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria. Discussion. ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era. Conclusions. ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies.