Nationwide multidisciplinary consensus on the clinical management of Merkel cell carcinoma: a Delphi panel

Abstract

Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous neuroendocrine carcinoma. The MCC incidence rate has rapidly grown over the last years, with Italy showing the highest increase among European countries. This malignancy has been the focus of active scientific research over the last years, focusing mainly on pathogenesis, new therapeutic trials and diagnosis. A national expert board developed 28 consensus statements that delineated the evolution of disease management and highlighted the paradigm shift towards the use of immunological strategies, which were then presented to a national MCC specialists panel for review. Sixty-five panelists answered both rounds of the questionnaire. The statements were divided into five areas: a high level of agreement was reached in the area of guidelines and multidisciplinary management, even if in real life the multidisciplinary team was not always represented by all the specialists. In the diagnostic pathway area, imaging played a crucial role in diagnosis and initial staging, planning for surgery or radiation therapy, assessment of treatment response and surveillance of recurrence and metastases. Concerning diagnosis, the usefulness of Merkel cell polyomavirus is recognized, but the agreement and consensus regarding the need for cytokeratin evaluation appears greater. Regarding the areas of clinical management and follow-up, patients with MCC require customized treatment. There was a wide dispersion of results and the suggestion to increase awareness about the adjuvant radiation therapy. The panelists unanimously agreed that the information concerning avelumab provided by the JAVELIN Merkel 200 study is adequate and reliable and that the expanded access program data could have concrete clinical implications. An immunocompromised patient with advanced MCC can be treated with immunotherapy after multidisciplinary risk/benefit assessment, as evidenced by real-world analysis and highlighted in the guidelines. A very high consensus regarding the addition of radiotherapy to treat the ongoing focal progression of immunotherapy was observed. This paper emphasizes the importance of collaboration and communication among the interprofessional team members and encourages managing patients with MCC within dedicated multidisciplinary teams. New insights in the treatment of this challenging cancer needs the contribution of many and different experts.

TRK Protein Expression in Merkel Cell Carcinoma Is Not Caused by NTRK Fusions

“…MCC is a rare cutaneous malignant tumor with neuroendocrine differentiation, increasing incidence, high risk of recurrence, and aggressive behavior [ 1 , 2 , 3 , 29 , 30 ]. Patients with localized MCC are treated with surgery followed by adjuvant radiotherapy and, usually, show low rates of tumor relapse and mortality [ 12 , 31 ]. Those with metastatic MCC, instead, are treated with immunotherapy, but about half of them are unresponsive and still do not have an effective alternative treatment [ 1 , 8 , 10 , 11 , 12 , 32 ].…”

“…Patients with localized MCC are treated with surgery followed by adjuvant radiotherapy and, usually, show low rates of tumor relapse and mortality [ 12 , 31 ]. Those with metastatic MCC, instead, are treated with immunotherapy, but about half of them are unresponsive and still do not have an effective alternative treatment [ 1 , 8 , 10 , 11 , 12 , 32 ].…”

“…MCPyV-negative MCC is associated with a higher number of molecular alterations and a worse prognosis than its MCPyV-positive counterpart [ 3 ]. MCC systemic treatment was based on platinum agents and etoposide chemotherapy until recently, when the paradigm shifted to immune checkpoint inhibitors that were demonstrated to be much more effective in attaining a durable response in many cases [ 1 , 8 , 10 , 11 , 12 ]; however, approximatively half the patients were unresponsive, thus underscoring a critical need to find novel treatments [ 1 ].…”

Introducing Radiotherapy in Metastatic Merkel Cell Carcinoma Patients with Limited Progression on Avelumab: An Effective Step against Primary and Secondary Immune Resistance?

“…In MCC patients with limited disease progression, RT might have a crucial role in reversing incoming refractoriness to immunotherapy, particularly in such a setting devoid of further effective systemic treatments. This use of RT has also been cautiously endorsed by a recent Delphi consensus, although no clinical validation exists [ 9 ].…”