Immune checkpoint blockade for Merkel cell carcinoma: actual findings and unanswered questions

Purpose: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma arising from the skin. We aimed to review and deal with some of the most relevant controversial topics on the correct use of immunotherapy for the treatment of MCC. Methods: The primary search was carried out via PubMed, EMBASE, and the Cochrane Library (until 31st May, 2018), while other articles and guidelines were retrieved from related papers or those referenced in these papers. Additionally, we performed an extensive search on ClinicalTrials.gov to gather information on the ongoing clinical trials related to this specific topic. Results: We performed an up-to-date critical review taking into account the results of both retrospective and prospective published studies evaluating these issues: Are there any predictive criteria of response to immunotherapy? What is the correct place of immunotherapy in the treatment algorithm of MCC? What is the best choice after immunotherapy failure? What to do with patients for whom immunotherapy is not been feasible or contraindicated? How long should immunotherapy be prolonged, and what follow-up should be offered after complete response? Conclusion: The therapeutic landscape of MCC is rapidly evolving: many open issues will probably be resolved, and many other questions are likely to arise in the next few years. The results of ongoing prospective clinical trials and of several other studies on these issues are eagerly awaited.