Recurrence and Mortality Risk of Merkel Cell Carcinoma by Cancer Stage and Time From Diagnosis
Authors: Aubriana M. McEvoy, Kristina Lachance, Daniel S. Hippe, Kelsey Cahill, Yasman Moshiri, Christopher W. Lewis, Neha Singh, Song Y. Park, Zoe Thuesmunn, Maclean M. Cook, Nora A. Alexander, Lauren Zawacki, Hannah Thomas, Kelly G. Paulson, Paul Nghiem
Journal: JAMA Dermatology (2022)

<h3>Importance</h3> Merkel cell carcinoma (MCC) often behaves aggressively; however, disease-recurrence data are not captured in national databases, and it is unclear what proportion of patients with MCC experience a recurrence (estimates vary from 27%-77%). Stage-specific recurrence data that includes time from diagnosis would provide more precise prognostic information and contribute to risk-appropriate clinical surveillance. <h3>Objective</h3> To estimate risk of stage-specific MCC recurrence and mortality over time since diagnosis. <h3>Design, Setting, and Participants</h3> This prospective cohort study included 618 patients with MCC who were prospectively enrolled in a Seattle-based data repository between 2003 and 2019. Of these patients, 223 experienced a recurrence of MCC. Data analysis was performed July 2019 to November 2021. <h3>Main Outcomes and Measures</h3> Stage-specific recurrence and survival, as well as cumulative incidence and Kaplan-Meier analyses. <h3>Results</h3> Among the 618 patients included in the analysis (median [range] age, 69 [11-98] years; 227 [37%] female), the 5-year recurrence rate for MCC was 40%. Risk of recurrence in the first year was high (11% for patients with pathologic stage I, 33% for pathologic stage IIA/IIB, 30% for pathologic stage IIIA, 45% for pathologic stage IIIB, and 58% for pathologic stage IV), with 95% of recurrences occurring within the first 3 years. Median follow-up among living patients was 4.3 years. Beyond stage, 4 factors were associated with increased recurrence risk in univariable analyses: immunosuppression (hazard ratio [HR], 2.4; 95% CI, 1.7-3.3;<i>P</i> &lt; .001), male sex (HR, 1.9; 95% CI, 1.4-2.5;<i>P</i> &lt; .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; 95% CI, 1.4-4.0;<i>P</i> = .001), and older age (HR, 1.1; 95% CI, 1.0-1.3;<i>P</i> = .06 for each 10-year increase). Among 187 deaths in the cohort, 121 (65%) were due to MCC. The MCC-specific survival rate was strongly stage dependent (95% at 5 years for patients with pathologic stage I vs 41% for pathologic stage IV). Among patients presenting with stage I to II MCC, a local recurrence (17 arising within/adjacent to the primary tumor scar) did not appreciably diminish survival compared with patients who had no recurrence (85% vs 88% MCC-specific survival at 5 years). <h3>Conclusions and Relevance</h3> In this cohort study, the MCC recurrence rate (approximately 40%) was notably different than that reported for invasive melanoma (approximately 19%), squamous cell carcinoma (approximately 5%-9%), or basal cell carcinoma (approximately 1%-2%) following definitive therapy. Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest.