A machine-learning modified CART algorithm informs Merkel cell carcinoma prognosis

Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with a high mortality rate. MCC staging is currently based on tumour primary size, clinical detectability of lymph node metastases, performance of a lymph node biopsy, and presence of distant metastases.

We aimed to use a modified classification and regression tree (CART) algorithm using available data points in the National Cancer Database (NCDB) to elucidate novel prognostic factors for MCC.

Retrospective cohort study of the NCDB and Surveillance, Epidemiology, and End Results (SEER) registries. Cases from the NCDB were randomly assigned to either the training or validation cohorts. A modified CART algorithm was created with data from the training cohort and used to identify prognostic groups that were validated in the NCDB validation and SEER cohorts.

A modified CART algorithm using tumour variables available in the NCDB identified prognostic strata as follows: I: local disease, II: ≤3 positive nodes, III: ≥4 positive nodes, and IV: presence of distant metastases. Three-year survival for these groups in the NCDB validation cohort were 81.2% (SE: 1.7), 59.6% (SE: 3.0), 38.0% (SE: 6.0), and 20.2% (SE: 7.0), respectively. These strata were exhibited greater within-group homogeneity than AJCC groups and were more predictive of survival.

Risk-stratified grouping of MCC patients incorporating positive lymph node count were strongly predictive of survival and demonstrated a high degree of within-group homogeneity and survival prediction. Incorporation of positive lymph node count within overall staging or sub-staging may help to improve future MCC staging criteria.