The Role of Systemic Therapies in Current and Emerging Opportunities for De-Intensification in Melanoma: a Scoping Review Protocol

Objective The purpose of this scoping review is to identify the role of systemic therapies in current and emerging opportunities to de-intensify systemic treatment of cutaneous melanoma. It will also seek to comment on the proportion of studies that include patient-reported outcomes and quality of life measures. Introduction With healthcare costs rising, focus is shifting towards maximising health outcomes per dollar. One approach to optimising value is through de-intensification, which is the rationalisation of routine treatment without compromising patient outcomes. Since 2013, successful clinical trials of high-cost immune checkpoint, BRAF and MEK inhibition have led to these drugs becoming ubiquitous in melanoma management. Pipeline therapies such as relatlimab and Tumour Infiltrating Lymphocyte (TIL) therapy are expected to have a similar or even greater cost. We hypothesize that neoadjuvant and response-directed strategies will be identified as well as the emerging potential of prognostic and predictive tools. Inclusion criteria This review aims to include studies of adult patients with cutaneous melanoma that report on de-escalation or de-intensification of internationally accepted standard-of-care systemic therapies or the use of systemic therapies to de-intensify subsequent surgery or radiotherapy. Systemic treatment across any stage of disease will be considered. A full-text English-language version must be available for a study to be eligible. Methods A systematic search strategy has been developed for MEDLINE, EMBASE and PubMed from 1 January 2013 to 30 June 2023. Additional texts will be sourced from grey literature, Google Scholar and reference scanning. Two authors will screen abstracts and full texts facilitated by the Covidence software. Disagreements will be resolved by consensus or a third reviewer. The first author (JS) will perform data extraction whilst a second author (FF) will review a random selection of papers to ensure consistent interpretation. De-intensification strategies will be categorised by concept, potential impact on resource utilisation and patient outcomes, and strength of evidence. Data will be synthesised qualitatively and quantitatively. Results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The results of this scoping review will directly inform a melanoma consumer and clinician survey exploring their perspectives on de-intensification strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript.