Epidemiological trends in Merkel cell carcinoma in southern France: a registry-based study

Dear Editor, Merkel cell carcinoma (MCC) (Fig. 1) is a cutaneous malignancy derived from Merkel cells. The crude incidence of MCC has increased from 0·2 to 0·6 per 100 000 persons between 1990 and 2006 in the U.S.A.1 Number of cases of Merkel cell carcinoma in Hérault from 1995 to 2011. This study reports and analyses the MCC‐related epidemiological and outcome data obtained from the Hérault Registry database. This work is original compared with prior reports as it is comprehensive, taking into account all MCC cases diagnosed in this well‐circumscribed area over a predefined period of time, and thus it presents reliable epidemiological data in the target population. This observational study collected data on all patients with MCC diagnosed between January 1993 and December 2011, residing in a defined administrative department of southern France and registered in the departmental cancer registry during this period. This registry collects and records all incident cancer cases occurring in the department in a continuous and exhaustive manner. A Classification Internationale des Maladies pour l'Oncologie code for MCC (8247/3) was introduced in 1990 and has been used for all patients diagnosed after 1995. All cases included in the study were validated through systematic checking of the medical records. Demographic data, tumour characteristics, treatment and patient outcome were reliably obtained. The variables used to analyse survival included the date of diagnosis, date of last news and vital status. Vital status was obtained through the National Institute of Statistics and Economic Studies and the National Directory of Identifying Individuals. The incidence and outcome analysis considered cases diagnosed from 1995 to 2011 with an end date of 30 June 2013 regarding last news collection. Crude and age‐standardized incidence rates per 100 000 inhabitants were computed. Standardized incidences were based on a direct standardization method and used both European and world standard population references. For survival analysis, 10‐year overall and net survival rates were estimated. Overall survival was assessed according to the actuarial Kaplan–Meier method. Net survival was estimated using the Pohar Perme method. All statistical analysis was carried out using R packages. Overall, 68 cases of MCC were recorded in the Hérault Tumour Registry between 1995 and 2011. The main demographic characteristics and description of tumours are summarized in Table 1. Characteristics of patients with Merkel cell carcinoma in Hérault from 1995 to 2011 and 1‐year, 5‐year and 10‐year overall and net survival rates for Merkel cell carcinoma in Hérault Characteristics of patients with Merkel cell carcinoma in Hérault from 1995 to 2011 and 1‐year, 5‐year and 10‐year overall and net survival rates for Merkel cell carcinoma in Hérault A total of 30 of 47 patients with localized disease, benefited from the currently recommended treatment in France, i.e. wide surgery and radiotherapy of the tumour area.2 Conversely, 15 patients had surgery alone, one patient had radiotherapy alone and one patient was treated with surgery, radiotherapy and chemotherapy. The sentinel lymph node (SLN) biopsy procedure was performed in six patients, revealing histological invasion in three of these patients. Among the nine patients with regional disease at diagnosis, eight benefited from surgery and radiotherapy (primitive tumour site and lymph node area), and one was treated with surgery alone. The patient with metastatic disease at diagnosis died before treatment. Immune deficiency at diagnosis was noted in five of 68 patients; two solid‐organ transplant recipients and three patients receiving immunosuppressive treatment for inflammatory diseases. Other cancers developed in a significant number of patients, which included 21 cutaneous carcinomas, 13 solid tumours, two haematological malignancies and two melanomas. Merkel cell polyomavirus sequences were searched for the period from 2008 to 2011. Of the eight patients tested, viral sequences were found in four. Between 1995 and 2011, crude incidence rates increased from 0·1 to 0·5 per 100 000 persons per year; European‐ and world‐standardized incidence rates increased from 0·1 to 0·3 and from 0·1 to 0·2 per 100 000 persons per year, respectively. The longest follow‐up was 17 years and the shortest was 2 years and 8 months. Of the 47 patients with localized disease at diagnosis, 27 did not relapse, two and eight patients experienced local and regional lymphatic recurrences, respectively, and nine had distant metastases. Of the nine patients with regional disease at diagnosis, four did not relapse, one experienced further regional nodal evolution, and subsequent distant metastatic evolution occurred in four cases. The median time for recurrence after initial MCC diagnosis, regardless of the stage at diagnosis, was 7 months with a maximum of 48 months. By the end of the survey, 43 of 68 patients had died. MCC was the main cause of death in 18 patients. Survival rates are shown in Table 1. The European‐standardized MCC incidence rates in France from 2006 to 2010 were estimated at 0·43 and 0·39 per 100 000 persons for men and women, respectively. For both sexes, the European‐standardized incidence rate during the same period in Hérault was 0·32 per 100 000 persons. The finding of an overall slightly lower incidence of MCC in one of the most sun‐exposed areas in France may be explained by a more adapted phototype and/or better sun protection. The net survival rates at 1 year in Hérault are consistent with French data, with 82% for Hérault and 84% for France, but the observed 5‐year survival rate is higher in Hérault than in France (50% and 42%, respectively) (submitted for publication). Some of our results are consistent with data from the literature. The MCC incidence rate in Hérault tripled during the survey period, in agreement with data from the U.S.A.1 and the Netherlands.3 Median age and tumour locations are also consistent with prior studies.1,3,4,5,6,7,8 The rates of patients with immune deficiency and a second cancer are also comparable with the literature data.5 The male/female ratio varies depending on the country. We found a male predominance in our study, as found in studies from Israel9 and U.S.A.,4 whereas there is a female predominance in northern Europe3,6,8 and more surprisingly in French global data. Other results from our study are less consistent with the data in the literature. Although rates of patients with localized and nodal disease at diagnosis in our study are comparable with data acquired from almost all countries,3,7,8,10 the rate of patients with metastatic disease was lower. However, this rate may have been underestimated as the stage at diagnosis was actually unknown in 16% of our patients. Furthermore, the SLN status was evaluated in 9% of our patients vs. 32% in U.S. patients.10 This may explain the lower rate of nodal disease compared with American studies.1,4,10 Initial treatment was more aggressive (surgery and radiotherapy) in Hérault than in the Netherlands,3 which is the only country where such therapeutic data are available. The authors thank the staff at the Hérault Tumour Registry for their assistance. Conflicts of interest: none declared.