Stage distribution, treatment patterns, and stage-specific survival in Merkel cell carcinoma before and after the immunotherapy era: A SEER analysis (2004–2022).

Abstract

e21556 Background: Merkel cell carcinoma (MCC) survival has improved in recent years. Whether this reflects earlier diagnosis or better stage-specific treatment is unclear. Methods: We performed a retrospective cohort study of MCC in the SEER database (2004–2022). Eras were defined as pre-immunotherapy proxy (Pre-IO, 2004–2015) and IO-era proxy (2016–2022). Stage at diagnosis was categorized as localized, regional, distant, or unknown (Summary Stage). Overall survival (OS) was assessed using the Kaplan–Meier method and stage-specific Cox models, adjusted for age (<65, 65–79, ≥80), sex, and race/ethnicity. Local therapy patterns (surgery, radiation) for localized/regional cases were examined by era and age. Results: Among 5,969 MCC patients (3,313 Pre-IO; 2,656 IO-era), stage distribution was localized 54.7%, regional 26.9%, distant 9.8%, unknown 8.6%. Compared with Pre-IO, the IO-era showed more regional (24.3%→30.2%; +5.8 pp) and less localized disease (56.6%→52.3%; −4.3 pp); distant stage was stable. Stage-specific survival improved in the IO-era proxy. Distant: median OS 10→12 mo; 2-yr OS 24.2%→40.6%; 5-yr OS 14.0%→23.4%; adjusted HR 0.75 (p=0.004). Regional: median OS 30→64 mo; 2-yr OS 54.5%→69.6%; 5-yr OS 38.0%→51.0%; HR 0.71 (p<0.001). Localized: median OS 71 mo→NR; 2-yr OS 72.5%→76.6%; 5-yr OS 53.3%→58.1%; HR 0.91 (p=0.11). Decomposition of the overall 2-yr OS (61.8%→69.1%) showed a minimal stage-shift effect (−0.61 pp) and gains driven by within-stage survival (+7.97 pp). Treatment patterns indicated age-related de-intensification. In localized IO-era MCC, surgery + RT occurred in 49.4% (<65) vs 27.4% (≥80). In regional MCC ≥80, surgery+RT declined (53.0%→42.1%) while neither therapy increased (7.1%→14.5%). Conclusions: MCC stage distribution showed minimal stage migration, yet OS improved substantially after 2016—especially in Regional and Distant disease. Survival gains were driven primarily by within-stage improvements rather than stage migration. Persistent age-related differences in local therapy suggest undertreatment of older adults. OS Pre-IO proxy vs IO-era proxy by stage. Stage Median OS (mo) 2-yr OS % 5-yr OS % Adjusted HR P value Localized 71→NR 72.5→76.6 53.3→58.1 0.91 0.11 Regional 30→64 54.5→69.6 38.0→51.0 0.71 <0.001 Distant 10→12 24.2→40.6 14.0→23.4 0.75 0.004 Unknown 31→34 55.8→52.0 35.6→38.8 1.06 0.66