IMPORTANCE 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. OBJECTIVE To estimate risk of stage-specific MCC recurrence and mortality over time since diagnosis. DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOMES AND MEASURESStage-specific recurrence and survival, as well as cumulative incidence and Kaplan-Meier analyses. RESULTS Among the 618 patients included in the analysis (median [range] age, 69 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; P < .001), male sex (HR, 1.9; 95% CI, 1.4-2.5; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; 95% CI, 1.4-4.0; P = .001), and older age (HR, 1.1; 95% CI, 1.0-1.3; P = .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). CONCLUSIONS AND RELEVANCEIn 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.

A Phase 1b, multi-center, randomized, double-blind, vehicle-controlled study was conducted in 48 adult patients with mild-to-moderate atopic dermatitis (AD). 17, and 14 patients received SB414 2% cream, SB414 6% cream and vehicle, respectively, twice daily for 2 weeks. SB414 showed trends suggestive of efficacy based on the change in eczema area severity index (EASI), itch numerical rating score (NRS) and target lesion severity score. Both SB414 2% and 6% were well tolerated, but 2% had a more favorable local tolerability profile with no quantifiable systemic exposure. Skin biopsies were obtained at baseline and Week 2 from a representative target lesion (LS) and from non-lesional skin (NL) at baseline. Gene expression analyses were conducted to assess lesional changes from baseline in the SB414 2%, 6% and vehicle-treated groups and difference between groups, as well as comparing with NL. Quantitative RT-PCR was performed using TaqMan Low Density Array (TLDA). Biomarkers from the Th2 and Th22 inflammatory pathways known to be highly associated with AD, including Interleukin 13 (IL-13), IL-4R, IL-5 and IL-22, were downregulated after two weeks of treatment with SB414 2%, achieving statistically significant 10.5 (p<0.01), 2.5 (p<0.01), 7.1 (p<0.05) and 7.5-fold (p<0.05) reductions over vehicle, respectively. The changes in Th2 and Th22 biomarkers as well as Th17 markers including IL-17A and IL-17F and clinical efficacy assessed as the percent change in EASI scores were significantly correlated in patients treated with SB414 2%. Overall, topical nitric oxide releasing 2% SB414 cream but not vehicle or 6% cream induced significant changes in AD biomarkers after 2 weeks of treatment. Further studies are ongoing.

Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin cancer, has a high rate (20%) of distant metastasis. Within a prospective registry of 582 patients with metastatic MCC (mMCC) diagnosed between 2003–2021, we identified 9 (1.5%) patients who developed cardiac metastatic MCC (mMCC). We compared overall survival (OS) between patients with cardiac and non-cardiac metastases in a matched case–control study. Cardiac metastasis was a late event (median 925 days from initial MCC diagnosis). The right heart was predominantly involved (8 of 9; 89%). Among 7 patients treated with immunotherapy, 6 achieved a complete or partial response of the cardiac lesion. Among these 6 responders, 5 received concurrent cardiac radiotherapy (median 20 Gray) with immunotherapy; 4 of 5 did not have local disease progression or recurrence in the treated cardiac lesion. One-year OS was 44%, which was not significantly different from non-cardiac mMCC patients (45%, p = 0.96). Though it occurs relatively late in the disease course, cardiac mMCC responded to immunotherapy and/or radiotherapy and was not associated with worse prognosis compared to mMCC at other anatomic sites. These results are timely as cardiac mMCC may be increasingly encountered in the era of immunotherapy as patients with metastatic MCC live longer.

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