Treatment of patients with locally advanced Merkel cell carcinoma: A multicenter study.
Authors: Dudzisz-Śledź Monika , Sobczuk Pawel , Kozak Katarzyna , Switaj Tomasz , Kosela-Paterczyk Hanna , Czarnecka Anna Malgorzata , Falkowski Slawomir , Rogala Pawel , Morysinski Tadeusz , Spalek Mateusz , Zdzienicki Marcin , Goryn Tomasz , Zietek Marcin , Cybulska-Stopa Bozena , Klek Stanislaw , Kaminska-Winciorek Grazyna , Ziolkowska Barbara , Szumera-Cieckiewicz Anna , Rutkowski Piotr 
Published: June 2021

e21566

Background: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with a high risk of recurrence and poor prognosis. The treatment of locally advanced disease includes surgery (SUR) and radiotherapy (RTH) to achieve high locoregional control rates. The sentinel lymph node biopsy (SLNB) is recommended procedure in cases without clinical nodal involvement. In selected cases, chemotherapy (CHT) may also be considered, but its role is not confirmed. This study aimed to analyze outcomes for locally advanced MCC pts treated in routine clinical practice. Methods: We conducted the retrospective analysis of data from 156 MCC pts treated with curative surgery in four oncological centers, diagnosed between 01/2010 and 12/2019, with data cut-off on 31/12/2020. The data collected included epidemiological and clinical information. Survival analyses were performed using the Kaplan-Meier method, log-rank test and multivariate Cox regression. Results: The median patient age at diagnosis was 72 years (30-94); 50.6% were male. The primary tumor (PT) locations were lower limbs (33.3%), upper limbs (30.1%), and head and neck (28.2%). MCC with no PT was diagnosed in 3.9%. In 62.0% the PT was located in the sun-exposed skin. The median tumor size was 25 mm (4-170). Lymph node (LN) involvement (clinical or positive SLNB or LND) at diagnosis was found in 26.9% (n = 42). The scar excision was done in 50.0% (positive in 16.6%), SLNB in 36.5% (positive in 10.5 %), 51.9% of pts received perioperative treatment, including RTH- 86.4%, CHT- 21%. The relapse rate was 38.3% (35.8% local-regional, 11.1% distant). With the median follow-up of 2.2-years, the median disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastases-free survival (DMFS) were not reached. The 1-year DFS, LRFS and DMFS rates were 65%, 68%, and 90%. The negative independent risk factors for DFS were male gender (HR 1.42, 95%CI 1.06-3.01), metastases in LN at diagnosis (HR 5.41, 95%CI 2.39-12.26), no SLNB in pts with no clinical metastases in LN (HR 5.45, 95%CI 2.41-12.3), and no perioperative RTH (HR 2.19, 95%CI 1.29-3.76). The median overall survival (OS) was 6.9 years (95%CI 4.64-9.15). The negative independent risk factors for OS were male gender (HR 1.95, 95%CI 1.16-3.27), age above 70 (HR 2.0, 95%CI 1.15-3.48), metastases in LN at diagnosis (HR 3.15, 95%CI 1.49-6.68), and no SLNB in pts with no clinical metastases in LN (HR 2.30, 95%CI 1.10-4.82). PT location, UV-exposure, and perioperative CHT or RTH were not independent risk factors for OS. Conclusions: Our results confirm that the MCC treatment should be done in an experienced multidisciplinary team. Male gender, nodal involvement at diagnosis, and no SLNB in pts without clinical metastases in LN are associated with poor prognosis in DFS and OS. The perioperative RTH improves the treatment outcomes and reduces disease progression risk but does not impact OS. Perioperative CHT does not affect pts survival.