title: Recurrence after complete resection and selective use of adjuvant therapy for stage I through III Merkel cell carcinoma.
abstract: BACKGROUND
  Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine neoplasm whose natural history is poorly understood. Here, the authors describe their experience with a large cohort of patients who were treated at a single institution to describe patterns of recurrence after curative therapy.
  
  
  METHODS
  Review of a prospective database was performed. Patient-related, tumor-related, and treatment-related variables were recorded, and the site and timing of initial recurrence were recorded. Factors associated with receipt of adjuvant therapy and recurrence were determined.
  
  
  RESULTS
  In total, 364 patients with stage I through III MCC who underwent complete resection were identified. Adjuvant local radiation therapy (RT), lymph node RT, and chemotherapy were received selectively by 23%, 23%, and 15% of patients, respectively. Factors associated with the receipt of adjuvant therapy included younger age, primary tumor features (larger size, lymphovascular invasion [LVI], positive margin excision), and increasing pathologic stage. With median follow-up of 3.6 years, 108 patients (30%) developed a recurrence, including 11 local recurrences (3%), 12 in-transit recurrences (3%), 43 lymph node recurrences (12%), and 42 distant recurrences (12%). Clinically involved lymph nodes, primary tumor LVI, and a history of leukemia/lymphoma were predictive of recurrence. The majority of recurrences (80%) occurred in patients who had clinically involved lymph nodes or patients who did not undergo pathologic lymph node evaluation.
  
  
  CONCLUSIONS
  A low recurrence rate in patients with clinically lymph node-negative MCC was achieved with adequate surgery (including sentinel lymph node biopsy) and the selective use of adjuvant RT for high-risk tumors. In contrast, patients with clinically lymph node-positive MCC had significantly higher rates of recurrence, especially distant recurrence. The authors concluded that contemporary natural history studies are critical in designing treatment pathways and clinical trials for MCC.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Fields
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Chou
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Pulitzer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kraus
authors.forename: Mary S
authors.initials: MS
authors.lastname: Brady
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Coit
mesh_terms: D000368:Aged; D015266:Carcinoma, Merkel Cell / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D015182:Lymphatic Irradiation; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D012008:Recurrence; D012878:Skin Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*