Merkel Cell Carcinoma: Evaluation of the Clinico-Pathological Characteristics, Treatment Strategies and Prognostic Factors in a Monocentric Retrospective Series (n=143)

Abstract

BackgroundMerkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The incidence of the disease has undergone a significant increase in recent years, which is caused by an increase in the average age of the population and in the use of immunosuppressive therapies. MCC is an aggressive pathology, which metastasizes early to the lymph nodes. These characteristics impose an accurate diagnostic analysis of the regional lymph node district with radiography, clinical examination and sentinel node biopsy. In recent years, there has been a breakthrough in the treatment of the advanced pathology thanks to the introduction of monoclonal antibodies acting on the PD-1/PD-L1 axis. This study aimed to describe the clinico-pathological characteristics, treatment strategies and prognostic factors of MCC.MethodsA retrospective cohort study was conducted involving 143 consecutive patients who were diagnosed and/or treated for MCC. These patients were referred to the Veneto Institute of Oncology IOV-IRCCS and to the University Hospital of Padua (a third-level center) in the period between December 1991 and January 2020. In the majority of cases, diagnosis took place at the IOV. However, some patients were diagnosed elsewhere and subsequently referred to the IOV for a review of the diagnosis or to begin specific therapeutic regimens.Results143 patients, with an average age of 71 years, were affected mainly with autoimmune and neoplastic comorbidities. Our analysis has shown that age, autoimmune comorbidities and the use of therapy with immunomodulating drugs (which include corticosteroids, statins and beta-blockers) are associated with a negative prognosis. In this sense, male sex is also a negative prognostic factor.ConclusionsAutoimmune and neoplastic comorbidities were frequent in the studied population. The use of drugs with immunomodulatory effects was also found to be a common feature of the population under examination. The use of this type of medication is considered a negative prognostic factor. The relevance of a multidisciplinary approach to the patient with MCC is confirmed, with the aim of assessing the risks and benefits related to the use of immunomodulating therapy in the individual patient.

Hemato-Oncological Diseases as Risk Factor for Recurrence or Metastasis of Pleomorphic Dermal Sarcoma

“…The risk of Merkel cell carcinoma is also significantly increased in patients with different types of immunosuppression including autoimmune diseases, neoplastic comorbidities, immunosuppression due to hemato-lymphoid disorders such as chronic lymphocytic leukemia/small lymphocytic lymphoma, and immune-modulating drugs or after solid organ transplantation. Moreover, immunosuppression significantly correlated with disease progression in these patients ( 34 – 37 ).…”

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

“…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 ].…”

Short-Interval, Low-Dose Peptide Receptor Radionuclide Therapy in Combination with PD-1 Checkpoint Immunotherapy Induces Remission in Immunocompromised Patients with Metastatic Merkel Cell Carcinoma

“…Conventional radiotherapy significantly improves relapse-free survival in adjuvant settings [ 8 ]. However, palliative radiation of MCC metastases is associated with poor distant metastasis-free survival [ 9 ]. A growing body of evidence suggests that external beam radiotherapy (EBRT), particularly when applied according to hypofractionated protocols as three single individual fractions of 5 Gy to 8 Gy, may sensitize the tumor in refractory patients to become responsive to re-challenging with ICI [ 10 , 11 ].…”