Beyond Event-Free Survival: A Multi-State Analysis of Local Recurrence, Metastasis, and Death in Soft Tissue Sarcoma
7 affiliations
- 1Sarcoma Service, Department of Orthopedics and Trauma, Kantonsspital Winterthur, 8400 Winterthur, Switzerland
- 2Department of Hip and Knee Surgery, Schulthess Clinic Zurich, 8008 Zurich, Switzerland
- 3Department of Neuroradiology, Heidelberg University, D-69117 Heidelberg, Germany
- 4Department of Biostatistics at the Epidemiology, Biostatistics and Prevention Institute, University of Zurich, 8001 Zurich, Switzerland
- 5Faculty of Health Sciences & Medicine, University of Lucerne, Frohburgstrasse 3, 6002 Luzern, Switzerland
- 6Sarcoma Service, Department of Radiation Oncology, Sarcoma Center, LUKS University Hospital, 6000 Lucerne, Switzerland
- 7Sarcoma Service, Department of Orthopedics and Trauma, Sarcoma Center, LUKS University Hospital, 6000 Lucerne, Switzerland
Abstract
Background/Objectives: Event-free survival (EFS) is widely used in soft tissue sarcoma (STS) research but combines clinically distinct outcomes such as local recurrence (LR), distant metastasis (DM), and death into a single endpoint. We aimed to decompose conventional EFS and characterize STS progression as a longitudinal process of transitions between clinically distinct disease states. Methods: Prospectively and retrospectively collected registry data from 662 patients with STS at two tertiary sarcoma centers were retrospectively analyzed. EFS was decomposed by first-event type, and longitudinal disease evolution was assessed using multi-state modeling and time-dependent Cox regression. Results: Among 585 patients included in the EFS analysis, first events were isolated LR in 114 (19.5%), DM in 106 (18.1%), synchronous LR and DM in 21 (3.6%), and death without documented recurrence in 19 (3.2%). In the full cohort, 151 deaths occurred. After multivariable adjustment, isolated LR showed a moderate but statistically imprecise association with mortality compared with the no documented LR or DM state (HR 2.55, 95% CI 0.93–7.02), whereas substantially greater mortality hazards were observed for isolated DM (HR 17.56, 95% CI 9.46–32.60) and combined LR and DM (HR 32.63, 95% CI 16.86–63.17). Conclusions: STS progression is characterized by clinically distinct, evolving disease states with markedly different prognostic implications. A disease-state framework complements conventional EFS by preserving the nature and longitudinal evolution of recurrence and may provide a more informative representation of STS progression.
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BibTeX
@article{scharer2026beyond,
title = {{Beyond Event-Free Survival: A Multi-State Analysis of Local Recurrence, Metastasis, and Death in Soft Tissue Sarcoma}},
author = {Markus Schärer and Philip Heesen and Gabriela Studer and Bettina Vogel and Bruno Fuchs and on behalf of the Swiss Sarcoma Network},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213414},
url = {https://www.mdpi.com/2072-6694/18/21/3414},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond Event-Free Survival: A Multi-State Analysis of Local Recurrence, Metastasis, and Death in Soft Tissue Sarcoma
AU - Markus Schärer
AU - Philip Heesen
AU - Gabriela Studer
AU - Bettina Vogel
AU - Bruno Fuchs
AU - on behalf of the Swiss Sarcoma Network
PY - 2026
DA - 2026/10/22
JO - Cancers
DO - 10.3390/cancers18213414
UR - https://www.mdpi.com/2072-6694/18/21/3414
AB - Background/Objectives: Event-free survival (EFS) is widely used in soft tissue sarcoma (STS) research but combines clinically distinct outcomes such as local recurrence (LR), distant metastasis (DM), and death into a single endpoint. We aimed to decompose conventional EFS and characterize STS progression as a longitudinal process of transitions between clinically distinct disease states. Methods: Prospectively and retrospectively collected registry data from 662 patients with STS at two tertiary sarcoma centers were retrospectively analyzed. EFS was decomposed by first-event type, and longitudinal disease evolution was assessed using multi-state modeling and time-dependent Cox regression. Results: Among 585 patients included in the EFS analysis, first events were isolated LR in 114 (19.5%), DM in 106 (18.1%), synchronous LR and DM in 21 (3.6%), and death without documented recurrence in 19 (3.2%). In the full cohort, 151 deaths occurred. After multivariable adjustment, isolated LR showed a moderate but statistically imprecise association with mortality compared with the no documented LR or DM state (HR 2.55, 95% CI 0.93–7.02), whereas substantially greater mortality hazards were observed for isolated DM (HR 17.56, 95% CI 9.46–32.60) and combined LR and DM (HR 32.63, 95% CI 16.86–63.17). Conclusions: STS progression is characterized by clinically distinct, evolving disease states with markedly different prognostic implications. A disease-state framework complements conventional EFS by preserving the nature and longitudinal evolution of recurrence and may provide a more informative representation of STS progression.
SN - 2072-6694
ER -