Postoperative radiotherapy in stage I–III Merkel cell carcinoma

• Published in: Radiotherapy and oncology 2022-01, Vol.166, p.203-211
• Main Authors: Levy, Sonja, Blankenstein, Stephanie A., Grünhagen, Dirk Jan, Jalving, Mathilde, Hamming-Vrieze, Olga, Been, Lukas B., Tans, Lisa, van Akkooi, Alexander C.J., Tesselaar, Margot E.T.
• Format: Article
• Language: English
• Subjects: Aged; Carcinoma, Merkel Cell - pathology; Carcinoma, Merkel Cell - radiotherapy; Carcinoma, Merkel Cell - surgery; Humans; Lymphatic Metastasis; Merkel cell carcinoma; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; PORT; Radiotherapy; Radiotherapy, Adjuvant; Recurrence; Retrospective Studies; Skin Neoplasms - pathology; Skin Neoplasms - radiotherapy; Skin Neoplasms - surgery; Survival
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2021.11.017

•PORT is associated with less recurrences in stage III MCC.•PORT does not improve MCC-related survival.•OS benefit of PORT in MCC patients is likely associated with selection bias. Postoperative radiotherapy (PORT) is currently recommended for the treatment of Merkel cell carcinoma. Nevertheless, deviations occur frequently due to the generally elderly and frail patient population. We aimed to evaluate the influence of PORT on survival in stage I-III MCC patients treated in the Netherlands. Patients were included retrospectively between 2013 and 2018. Fine-Gray method was used for cumulative incidence of recurrence and MCC-related death, cox regression was performed for overall mortality. Analyses were performed in patients with clinical (sentinel node biopsy [SN] not performed) stage I/II (c-I/II-MCC), pathologic (SN negative) stage I/II (p-I/II-MCC) and stage III MCC (III-MCC), separately. Propensity score matching (PSM) was performed to assess confounding by indication. In total 182 patients were included, 35 had p-I/II-MCC, 69 had c-I/II-MCC and 78 had III-MCC. Median follow up time was 53.5 (IQR 33.4–67.4), 30.5 (13.0–43.6) and 29.3 (19.3–51.0) months, respectively. Multivariable analysis showed PORT to be associated with less recurrences and reduced overall mortality, but not with MCC-related mortality. In stage III-MCC, extracapsular extension (sub-distribution hazard [SDH] 4.09, p = 0.012) and PORT (SDH 0.45, p = 0.044) were associated with recurrence, and ≥ 4 positive lymph nodes (SDH 3.24, p = 0.024) were associated with MCC-related mortality. PORT was associated with less recurrences and reduced overall mortality in patients with stage I-III MCC, but not with MCC-related mortality. Trends in overall survival benefit are likely to be caused by selection bias suggesting further refinement of criteria for PORT is warranted, for instance by taking life expectancy into account.