BACKGROUND: The incidence of MCC is increasing. Immuno-oncology agents are the standard of care in stage IV MCC. However, less is known for stage I-III MCC, and there is a need for new treatments to minimize progression to late stages. A systematic literature review was conducted to understand how patients with early-stage MCC are treated and assess efficacy and safety of current therapies. METHODS: Embase and PubMed were used to identify publications from January 2014 to October 2019, capturing studies with efficacy and safety outcomes with relevant interventions in patients with stage I-III MCC. The review included monotherapies or combinations of pharmacological treatments, radiotherapy (RT), chemotherapy (CT), and surgery (SUR). Adjuvant (adj), neoadjuvant, and maintenance/consolidation therapies after SUR were included. First, 2 reviewers independently reviewed titles and abstracts for eligibility. Second, the full text of all selected titles were reviewed. Discrepancies were reconciled by an independent reviewer. The 2 reviewers carried out the data extraction and quality check. RESULTS: There were 72 studies included in the review, comprising 5 clinical trials, 57 retrospective and 4 prospective studies, 3 case studies/reports, and 3 economic studies. The identified treatments in stage I-III MCC were RT alone, SUR alone, adjCT, SUR + adjRT, and SUR + adjRT + adjCT. Overall survival (OS) was the most commonly reported efficacy outcome. One large study (n=6908) showed improved OS with SUR + adjRT vs SUR alone in stages I and II; however, this was not shown in stage III. Treatment with adjCT did not demonstrate improved OS in any of stages I-III. Only 4 studies with neoadjuvant treatment were identified in this review. The table below summarizes key efficacy results for OS. Limited safety data regarding RT, SUR, and SUR + adjRT were reported in 4 studies in patients with stage I-III MCC. CONCLUSIONS: While SUR + adjRT was the most commonly used treatment, there is no clear standard of care in stages I-III MCC. Some treatments show benefits; however, there still remains an unmet need to improve treatment outcomes, and safety data are limited. A majority of studies were retrospective and had limited sample sizes; hence, findings should be interpreted with caution. There is potential to assess newer immuno-oncology agents in this patient population.
Summary of Efficacy Results for OS