Introducing MCC-PS: a Novel Prognostic Score for Merkel Cell Carcinoma

Introduction: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a poor prognosis, which only improved with the introduction of immunotherapies. An MCC prediction model with high diagnostic accuracy is lacking. The aim was to develop an MCC prognostic score (MCC-PS) based on combinations of previously proposed risk factors.

Methods: A multicentric, retrospective study was conducted to develop MCC-PS, which included age, neuron-specific enolase (NSE), C-reactive protein (CRP), creatinine, bilirubin, and international normalized ratio (INR). Creatinine, bilirubin, and INR were used to calculate the model of end-stage liver disease (MELD) score. A total of 98 patients were included in the study, including 36.7% with stage I according to American Joint Committee on Cancer 2018 ( = 36), 30.6% with stage II ( = 30), 25.5% with stage III ( = 25), and 7.1% with stage IV ( = 7). Survival data of MCC patients were correlated with selected laboratory parameters and risk factors. Primary endpoint was MCC-specific survival (MSS) and the secondary endpoint was progression-free survival. Several statistical methods were used to develop the prognostic score, including correlation analysis, Kaplan-Meier curves, Cox regression, and time-dependent receiver operating characteristic analysis.

Results: The MCC-PS is based on the sum of the following baseline variables: elevated CRP (≥5.5 mg/l), elevated NSE (≥22.8 µg/l), MELD score ≥ 11, and age ≥ 75 years. An MELD score ≥ 11 was scored as 4 points, elevated NSE level as 3 points, elevated CRP level as 2 points, and age ≥ 75 years as 1 point. A high-risk group according to the MCC-PS was characterized by a score of 4 or more points. The high-risk group was associated with a worse prognosis than the low-risk group (1-year MSS 62%, 2-year 43.1%, 5-year 17.6% as compared to 1-year MSS 79.5%, 3-year 75%, 5-year 72%). Notably, the developed MCC-PS predicts MCC outcome measures with high accuracy (3-year MSS: area under the curve (AUC) 0.934, sensitivity 87.5% and specificity 82.2%; 5-year MSS: AUC 0.93, sensitivity 89% and specificity 82%).

Conclusion: MCC-PS is the first prognostic score predicting MCC outcome with a high accuracy based on five easily available laboratory parameters and patient's age. An MCC-PS of 4 or more indicates a high-risk patient associated with a poor prognosis.