Postoperative radiotherapy in Merkel cell carcinoma (MCC).

Abstract

9575 Background: MCC is a rare and aggressive neuroendocrine malignancy of the skin. Postoperative radiotherapy (PORT) is recommended by current guidelines to reduce recurrences and improve survival in patients with locoregional MCC. However, evidence supporting these recommendations is conflicting and deviations from the protocol occur frequently, due to the generally elderly and frail patient population. We aim to evaluate the influence of PORT on survival in stage I-III MCC patients treated in the Netherlands. Methods: All patients with stage I-III MCC treated in three referral centers between 2013 and 2018 were included retrospectively. Recurrence free survival (RFS) and disease specific survival (DSS, including death from unknown causes) were compared between patients with and without PORT. Prognostic factors for DSS were analyzed using Kaplan-Meier curves, logrank test and cox regression. Since sentinel node biopsies (SN) are frequently omitted in this patient population, analyses were performed in patients with clinical (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 possible confounding by indication. Results: In total 219 patients were included, of whom 54 had p-I/II-MCC, 82 had c-I/II-MCC and 83 had III-MCC. Median follow up time was 53.4 (IQR 32.8-62.4), 28 (11.8-43.3) and 30.8 (19.5-50.0) months, respectively. PSM identified no confounding by indication, analyses were therefore performed in the unmatched cohort. Majority of recurrences were regional in p-I/II-MCC (77.8%) and c-I/II-MCC (74.2%), and distant in III-MCC (61.7%). RFS was significantly different across all stages (p<0.001), DSS was similar for patients with c-I/II-MCC and III-MCC, which was significantly worse compared to patients with p-I/II-MCC (p=0.003). Survival times are shown in table. PORT did not improve RFS and DSS in patients with p-I/II-MCC and c-I/II-MCC. In patients with III-MCC, PORT was associated with improved RFS, but not with DSS. Multivariable analysis identified male gender (hazard ratio (HR) 1.94, p=0.030), performance status (PS) of 3 (HR 3.87, p=0.014) and an unknown PS (HR 5.45, p=0.004), primary tumor on the trunk (HR 2.67, p=0.008), c-I/II-MCC (HR 5.38, p=0.001) and III-MCC (HR 6.44, p<0.001) as predictors for DSS. Effect of PORT was not significant. Conclusions: In this retrospective cohort PORT did not show a DSS benefit in patients with stage I-III MCC. RFS was improved by PORT in III-MCC. PSM showed no confounding by indication.[Table: see text]