INVESTIGATIVE REPORT
699 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV
Outcome of Combined Treatment of Surgery and Adjuvant Radiotherapy in Merkel Cell Carcinoma
Eckhard FIEDLER 1 and Dirk VORDERMARK 2
1
Department of Dermatology, and 2 Department of Radiation Oncology, Martin Luther University Halle-Wittenberg, Halle( Saale), Germany
In recent analyses of Merkel cell carcinoma, prognosis is poor even in stages I and II. We performed a monocentric retrospective study of 37 consecutive cases with Merkel cell carcinoma stage I to III treated with a combination of surgery and adjuvant radiation to evaluate progression-free and overall survival. The median primary tumour diameter was 17.9 mm. Cases consisted of 31 primary tumours, of which 13 had negative sentinel lymph node biopsy( IA n = 10 and IIA n = 3) and 18 no sentinel lymph node biopsy( IB n = 15 and IIB n = 3), 2 tumours with positive sentinel lymph node biopsy( IIIA) and 4 with local macrometastasis( IIIB). The median age was 71 years and the median follow-up was 60.4 months. The 5-year progressionfree survival was 83.8 % and 5-year disease-specific survival was 95.7 %( overall survival 93.0 %). So far, our results show a high survival rate with combined treatment of surgery and adjuvant radiotherapy in early tumour stages of Merkel cell carcinoma.
Key words: Merkel cell carcinoma; MCC; combined treatment; adjuvant radiotherapy.
Accepted Jan 29, 2018, Epub ahead of print Jan 30, 2018 Acta Derm Venereol 2018; 98: 699 – 703.
Corr: Eckhard Fiedler, MD, Department of Dermatology, Martin Luther University Halle-Wittenberg, Ernst-Grube-Straße 40, DE-06120 Halle( Saale), Germany. E-mail: eckhard. fiedler @ halle-hautarzt. de
In the literature, Merkel cell carcinoma( MCC) is described as an aggressive metastasizing neuroendocrine skin tumour. In current papers, high mortality rates are reported even in low tumour stages( 1, 2). A 5-year overall survival( OS) rate of 64 % is reported for localized tumours( stage I and II), and 39 % for loco-regional lymph node metastases( stage III)( 2). Beside excision with wide margins, adjuvant radio therapy( RT) of the primary tumour site and regional lymph node bed in early tumour stages has been widely recommended for more than 20 years( 3), though it still remains controversial( 4). The question of suitable tumour stages for systemic approaches arises in light of new therapeutic strategies, including PD1 inhibitors( 2, 5).
This research is a retrospective monocentric study of consecutive patients with MCC who were treated with excision and adjuvant RT and followed up at the Department of Dermatology of the Martin Luther University Halle-Wittenberg from 2000 to 2017.
SIGNIFICANCE
In literature Merkel cell carcinoma is depicted as a rare but aggressive and metastasizing skin tumour. Our results of 37 consecutive patients treated by combined surgery and adjuvant radiotherapy show a low regional recurrence rate as well as a high 5-year disease-specific survival rate( 95.7 %). The combination of surgery and adjuvant radiotherapy may improve the management of localized MCC with or without limited involvement of loco regional lymph nodes. Because of the discrepancy between the effects of combined therapy versus surgery alone systemic therapies could also be considered if due to contraindication to RT a combined therapy is impossible.
MATERIAL AND METHODS
Between 2000 and 2017, 41 consecutive patients with histologically and immunohistologically-confirmed diagnosis of MCC came for therapy and follow-up care to the Department of Dermatology.
If there was neither contraindication nor refusal of treatment, an R0-resection – if possible with wide excision margins – and adjuvant RT of the primary tumour site and regional lymph node bed were performed. Doses of 48 to 60 Gy were used. Due to side effects of radiotherapy 2 patients received 28 Gy and 34 Gy only. After therapy, the patients were transferred to regular follow-up.
Sentinel lymph node biopsy( SLNB) was performed in 13 patients( 35.1 %). The median excision margin was dependent on the location of the primary tumour site: limbs 18 mm( n = 24; range 0.1 – 30), head and neck 10 mm( n = 11; range 1.0 – 20), and trunk 20 mm( n = 2; range 20.0 / 20.0). The median excision margin was 10 mm in all 37 cases. Cases with primary distant metastases( stage IV) or inoperable bulky disease were excluded, as were cases in which the patient refused combined treatment( excision and RT). Ten-year follow-up included clinical( months 0 to 48: every 3 months, months 48 to 120: every 6 months) and ultra sound examination of primary tumour site and regional lymph nodes( months 0 to 24: every 3 months, months 24 to 60: twice a year, months 60 to 120: once a year), chest X-rays and abdominal ultra sound: months 0 to 120: once a year. TNM staging was made according to UICC TNM 7 th edition( 6). Statistics including Kaplan Meier survival analysis were performed using IBM SPSS statistical software.
RESULTS
Of 41 MCC patients, 3 were in need of systemic therapy( 2 stage IV and 1 with bulky metastatic disease( stage III)). Another patient refused radiotherapy. The remaining 37 cases are shown in Table I. The group under
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica. doi: 10.2340 / 00015555-2895 Acta Derm Venereol 2018; 98: 699 – 703