There is little randomised evidence of the use of adjuvant therapy in the management of Merkel cell carcinoma. Historically, surgery has been the mainstay of treatment but this has been associated with high rates of locoregional failure if not followed by post-operative radiotherapy. The addition of wide-field radiotherapy to surgery has become the standard of care and has been shown to improve locoregional control in this patient group.
A meta-analysis,r SEER report and numerous single institution retrospective studiesr have reported the benefit to locoregional control and local recurrence with the use of adjuvant radiotherapy.
The meta-analysis by Lewis et alr of 1254 patients from 132 studies reported that patients treated with combination therapy (surgery and radiation therapy) had improved outcomes and were significantly less likely to develop local recurrence (HR, 0.27; p<0.001). Local recurrence rates after surgery and combination therapy were, 71% (at 1 year) and 61% (at 5 years) for surgery compared with 90% (1 year) and 88% (5 years) after combination therapy. Local recurrences at 5 years were three times less likely (12% vs 39%, p<0.001) if adjuvant radiation was given and a similar association was found for regional recurrences (23% vs 56%, p<0.001). See figure 1 below.
© Arch Dermatol Lewis 2006r
Management of draining lymph nodes is an essential component of treatment. Sentinel lymph node biopsy may be useful to guide either elective lymph node dissection or delineation of radiotherapy fields. Radiotherapy to nodes, either as definitive management or as adjuvant treatment after nodal dissection has been reported to improvement regional control.
The study by Jouray et alr included 83 patients with stage 1 Merkel cell carcinoma treated by wide excision and local radiotherapy; patients were then randomised to adjuvant regional node radiotherapy (n=39) or observation (n=44). Median follow up was at 58 months for all patients. Overall survival (OS) at 3 and 5 years was 92.3% and 89.2% respectively for the entire group. Probability of regional recurrence (PRR) for both groups was 8.4% at 1year and 17.7% at 5 years. The progression free survival (PFS) was not statistically significant between the groups although it tended to be higher in the RT group with 89.7% vs 81.2% at 3 years. OS rates didn’t differ between groups however the study demonstrated a significantly lower PRR in the group receiving regional node radiotherapy with 16.7% in the observation arm versus 0% in the treatment arm (p=0.007).
Figure 2 Patients’ overall survival according to the randomization group
Group A: n = 39 patients; group B: n = 44 patients; p=0.989.
Figure 3. Regional recurrence probability according to the randomization group
Group A: n = 39 patients; group B: n = 44 patients; p=0.007
The group A curve intermingles with the abscises line as no patient experienced regional recurrence in this group.
Figure 4. Progression-free survival according to the randomization group
Group A: n = 39 patients; group B: n = 44 patients; p=0.4
© Ann Oncol Jouray 2012r
Based on this, and the proclivity of Merkel cell carcinoma to spread via dermal lymphatics to locoregional nodes, we recommend that radiotherapy fields encompass the primary with a wide-field, in-transit lymphatics and the first echelon of draining lymph nodes.
Concurrent chemotherapy remains an active area of investigation, with early studies suggesting high locoregional control rates.