SerUM markers in MERkel Cell Carcinoma patients: a longitudinal moniTorIng study for optiMization of European guidelines.

Merkel cell carcinoma (MCC) is a rare aggressive skin carcinoma. Approximately
80% of MCC are related to the Merkel Cell Polyomavirus (MCPyV).
Although rates of relapse are high, the follow-up strategy lacks consensus.
Patients are usually assessed clinically every 3 to 6 months for the first 2-3
years, and every 6 to 12 months thereafter. In the European guidelines,
patients with early stages are monitored with clinical examination and
ultrasonography of lymph nodes, while wholebody imaging is optional in patients
with stage III disease, on a yearly basis for 5 years. Such strategy may
prevent the diagnosis of infraclinical recurrences, whereas patients could
still be treated with surgery or radiation therapy. Until 2017, patients with
advanced disease were treated with chemotherapies, with no long-term benefit.
Immunotherapies with PD-1/PD-L1 inhibitors currently allow durable responses in
50% of such patients. This major change in the management of MCC patients
argues for a follow-up strategy that would allow early diagnosis of
infra-clinical metastases, when tumoral burden is still low. Given that all
patients cannot be monitored by systematic regular imaging, additional
non-invasive tools are needed. Blood-based biomarkers as a surrogate of tumor
burden are advantageous as they can be repeated over time, providing guidance
on when imaging is necessary. The study aims to assess two blood biomarkers,
MCPyV T-Ag antibodies and cell-free miR-375, in a prospective fashion from
baseline diagnosis, in a cohort of 150 European MCC patients

PRIMARY OBJECTIVE
To assess the diagnostic performances (specificity, sensitivity, positive and
negative predictive values) of monitoring blood biomarkers (T-Ag antibodies and
miR375 levels) for detection of recurrence of disease during follow up.

SECONDARY OBJECTIVES
To assess the diagnostic performances (specificity, sensitivity, positive and
negative predictive values) of monitoring blood biomarkers (T-Ag antibodies and
miR375 levels) for progression of disease during follow up. To assess the
diagnostic performances (specificity, sensitivity, positive and negative
predictive values) of each blood monitoring strategy (either use of biomarker
1, biomarker 2 or both) for detection of recurrence of disease during follow
up. To assess clinical factors and biomarkers at baseline that are associated
with outcome (recurrence, response to treatments and death).

Prospective clinical trial

during regular meetings, 5 times 5 ml blood will be collecting in a period of 1
year.