Outcomes after first recurrence of Merkel cell carcinoma: A retrospective cohort of 159 patients

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of 40%. Data on outcomes after a first recurrence remains scarce. OBJECTIVE: To evaluate survival and prognostic factors after a first recurrence of MCC. METHODS: We analyzed patients from a historical-prospective cohort (1998-2023) who developed recurrence after completion of treatment for stage I-III disease. The primary endpoint was disease-specific survival (DSS) after first recurrence. Secondary objectives included identification of prognostic factors for MCC-related death after first recurrence. RESULTS: Among 383 stage I-III patients, 159 (41.5%) recurred. Median DSS after first recurrence was 18.3 months (95% CI 12.8-75.3). Among patients receiving systemic therapy at recurrence, median DSS was shorter in those receiving chemotherapy/targeted therapy vs immunotherapy (10.4 months vs not reached, p = 0.015). In multivariable analysis, immunosuppression (hazard ratio (HR) 2.69) and early recurrence (<6 months) (HR 1.92) were associated with increased mortality, while locoregional recurrence (HR 0.45) and radiotherapy administered at recurrence (HR 0.45) were associated with a reduced risk of death. Absence of systemic treatment at first recurrence was associated with a significantly higher risk of death compared with ICI therapy (HR 3.04). LIMITATIONS: Retrospective design, low rates of sentinel lymph node biopsy procedures, heterogeneity of therapeutic regimens over two decades. CONCLUSION: Immunosuppression, early recurrence, and distant recurrence are associated with poor prognosis after first recurrence of MCC, whereas radiotherapy administered at recurrence is associated with improved survival. Although immune checkpoint inhibitors did not retain an independent prognostic impact in multivariable analysis, univariate findings suggest a potential survival benefit in selected patients receiving systemic therapy.