LAUSR

Background No adequate biomarker for Merkel cell carcinoma (MCC) has been identified. Serum neuron-specific enolase (NSE) has been tested and is commonly used as a biomarker for several other small cell malignancies. However, the role of NSE in MCC is still unclear. The purpose of this study was to investigate the role of NSE as a biomarker in MCC. Methods A prospective cohort of MCC patients was analyzed using Kaplan–Meier curves with log-rank test, ROC curves, Cox regression, and mixed models. A separate evaluation was performed for patients treated with immunotherapy. Results Eighty-four patients were included [47 males, median age 71 years, stages I & II, III, and IV MCC in respectively 39 (46%), 42 (50%), and 4 (3%) patients at time of diagnosis] with 565 NSE samples (median 15; interquartile range 12.6–22 ng/ml). Baseline NSE had no association with prognosis. NSE correlated with extent of disease ( P  = 0.01) and increased with 15 ng/ml per class (no tumor load, localized MCC, regional or distant metastases, respectively). NSE was able to detect progression (AUC 0.89). A NSE of 18.2 ng/ml was considered the most optimal level for clinical use (sensitivity 91%, specificity 78%, PPV 48%, NPV 98%). During immunotherapy ( N  = 23; 248 NSE values), all complete responders ( N  = 10) had a normalized NSE (< 18.2 ng/ml), all partial responders ( N  = 5) had a decreasing NSE. In nonresponders ( N  = 8), all NSE levels remained elevated. Conclusions NSE could be a valuable biomarker in MCC. NSE correlates with extent of disease; it is able to rule out progression and distinguishes responders from nonresponders during immunotherapy.