Cutaneous Merkel cell carcinoma

Abstract

Purpose

The aim of this study was to describe the treatment outcomes of patients with cutaneous Merkel cell carcinoma managed with curative intent.

Materials and Methods

Between December 1984 and November 2009, 40 patients with previously untreated Merkel cell carcinoma were managed with curative intent with radiotherapy alone (3 patients) or combined with surgery (37 patients). Adjuvant chemotherapy was administered to 11 patients. Primary sites were the following: head and neck, 32 patients; extremities, 6 patients; and trunk, 2 patients. Patients were staged according to the Yiengpruksawan staging system: stage I, local disease; stage II, regional disease; and stage III, distant metastases. Twenty-four patients had stage I disease, and 16 patients had stage II disease. Median follow-up on all patients was 3.0 years (range, 0.6–15.6 years). Median follow-up on survivors was 4.2 years (range, 2.2–14.2 years).

Results

The 5-year outcomes were local control, 92%; regional control, 78%; local-regional control, 79%; distant metastasis-free survival, 57%; cause-specific survival, 45%; and overall survival, 36%. The 5-year outcomes for those with stage I vs stage II disease were the following: local-regional control, 87% and 67% (P = .1607); distant metastasis-free survival, 71% and 37% (P = .0073); cause-specific survival, 58% and 27% (P = .0090); and overall survival, 48% and 18% (P = .0037). Local-regional recurrences were observed in 6 patients; one patient was successfully salvaged. Severe complications were observed in 3 patients.

Conclusions

Radiotherapy alone or combined with surgery results in a high local-regional control rate. The main mode of recurrence is distant. Approximately one half of patients are cured.

Introduction

Cutaneous Merkel cell carcinoma (MCC) is a rare skin cancer of neuroendocrine origin that was first described by Toker in 1972 [1], [2], [3]. The age-adjusted incidence is approximately 0.24 to 0.44 per 100 000 person years [3]. Although the incidence is reportedly rising, it is unclear whether this represents a true increased incidence or an increased recognition of MCC. Risk factors for MCC are sun exposure and immune suppression, including chronic lymphocytic leukemia, solid organ transplant, and HIV [4], [5], [6]. Human polyoma virus appears to be etiologic in a significant proportion of patients with MCC; the presence of human polyoma virus DNA in the MCC cells may be associated with an improved prognosis [5]. Heath et al [7] reported on 195 patients with MCC treated at 5 institutions (Boston, 3; Seattle, 2) between 1980 and 2007; 81% were located in ultraviolet-exposed sites. MCC exhibits a slight male preponderance [2], [8]. Mojica et al [8] reported on 1665 patients from the SEER database from 1973 to 2000; men accounted for 59% and women for 41% of patients. The vast majority (more than 90%–95%) was white and approximately 90% were older than 50 years [3], [7]. Mojica et al [8] reported a median age of 76 years (range, 22–101 years). The most common sites include the head and neck and extremities. Andea et al [3] reported on 156 patients treated at the Memorial Sloan Kettering Cancer Center between 1980 and 2005. They observed the following site distribution: extremity, 42%; head and neck, 37%; buttocks, 16%; and trunk, 5% [3].

Most MCCs appear relatively innocuous at diagnosis. Heath et al [7] reported a median maximum tumor diameter of 1.8 cm; 88% of patients were asymptomatic despite a history of rapid growth in 63% during the 3 months before diagnosis. The most common color was red/pink in 56%, followed by blue/violaceous in 26% [7]. The lesion was thought to be benign before biopsy in 56% [7].

The diagnostic evaluation of the patient with MCC includes taking a thorough history, physical examination, chest radiograph, and computed tomography of the primary site and regional lymphatics. Fluorodeoxyglucose positron emission tomography–computed tomography will likely contribute to altered staging and a change in the treatment plan and should be obtained in most patients [9]. The value of sentinel lymph node biopsy (SLNB) in the routine management of patients with MCC is debatable and depends on treatment philosophy [10]. On one hand, if patients with a pathologically negative SLNB were followed up and adjuvant nodal radiotherapy (RT) was withheld, then SLNB would be valuable to define this subset of patients. In addition, one could argue that those with pathologically positive SLNBs could be considered for adjuvant chemotherapy because of the increased risk of distant metastases.[11] Alternatively, adjuvant chemotherapy has not been shown to improve outcome in high-risk patients and, because of the high likelihood of subclinical disease in clinically negative regional nodes, it is the authors' bias to electively irradiate these regions regardless of SLNB status [11], [12]. Thus, in the latter instance, SLNB does not meaningfully contribute to management decisions.

Several staging systems have been described for MCC [13], [14]. The staging system described by Yiengpruksawan et al [13] is straightforward and has been widely used: stage I, local disease; stage II, regional disease; and stage III, distant metastasis. The staging system described by the American Joint Committee in Cancer is more complex and is ill-suited to an entity that is relatively rare and where the number of patients included in most single-institution outcome studies is relatively small [14]. Mojica et al [8] reported the following stage distribution in 1665 patients from the SEER database: stage I, 55%; stage II, 31%; stage III, 6%; and no data, 8%.

Surgery and RT are the mainstays of treatment for patients with stage I and II MCC [10], [12], [15], [16], [17], [18], [19], [20].

Although a subset of patients with stage I disease may be managed with surgery alone, the high likelihood of subclinical disease in the clinically negative regional lymphatics and the modest risk of in-transit metastases suggest that most patients benefit from the addition of RT [8], [20]. Patients with stage II disease have approximately a 75% local-regional control rate after RT alone or combined with surgery [15], [17]. Although debatable, the addition of surgery to RT probably results in improved local-regional control [15], [16], [17], [21].

The purposes of this article are to report the outcomes of a series of patients with MCC treated at our institution and to discuss the optimal management of patients with this disease.