A new Policy Review by EORTC–ESTRO published in The Lancet Oncology addresses one of the field’s most persistent challenges: selecting meaningful clinical trial endpoints that reflect both disease biology and real-world treatment strategies.
Title: Clinical trial endpoints for metastases-directed therapy in oligometastatic cancer a review and Delphi consensus on behalf of the EORTC–ESTRO OligoCare consortium
Authors: Joachim Widder, Guus Bol, Inga-Malin Simek, Felix Ehret, Hoda Abdel-Aty, Selma Basic, David Chuter, Jacqueline Daly, Patricia Fairbrother, Donjeta Zeqa, Frank Aboubakar Nana, Verane Achard, Stefanie Corradini, Dora Correia, Dirk De Ruysscher, Anne-Marie Dingemans, Corinne Faivre-Finn, Silke Gillessen, Marianne Guren, Lizza Hendriks, Matthias Guckenberger
Published in: The Lancet Oncology, Volume 27, Issue 5, May 2026
Background
Oligometastatic cancer is increasingly recognized as a distinct clinical state between localized and widely metastatic disease, where a limited number of lesions may be amenable to local therapies such as stereotactic radiotherapy, surgery, or ablation. However, evaluating the true impact of these approaches remains challenging. Traditional endpoints such as overall survival and progression-free survival, while well established, do not always capture the dynamic nature of oligometastatic disease, particularly in settings where repeated local interventions are feasible and clinically meaningful .
Methods
To address this issue, investigators conducted a systematic review of international clinical trial registries alongside a structured Delphi consensus process. A total of 150 trials evaluating metastases-directed therapy were analyzed, followed by four rounds of expert consensus involving clinicians and patient representatives. The goal was to identify endpoints that are applicable across tumor types and better aligned with contemporary treatment strategies, particularly those integrating systemic therapies.
Results
The analysis revealed substantial heterogeneity in the endpoints currently used in clinical trials. Progression-free survival and overall survival remain the most commonly reported primary endpoints, yet both were recognized as having important limitations in this context. Overall survival, although considered the most definitive outcome, requires prolonged follow-up and is influenced by subsequent treatments, making it difficult to isolate the effect of metastases-directed therapy.
Through the Delphi process, consensus was reached that overall survival should remain a key endpoint, but not as a standalone measure. Additional endpoints were identified as particularly relevant for oligometastatic disease. Among these, polymetastatic progression-free survival and systemic therapy–free survival emerged as meaningful alternatives, especially in trials that combine local and systemic treatments. These endpoints acknowledge that new lesions or limited progression do not necessarily represent treatment failure, as repeat local therapy can still achieve disease control.
Importantly, patient representatives emphasized the relevance of quality of life, highlighting time-to-deterioration as a critical outcome that should be incorporated into future trial designs.
Clinical Implications
These findings underscore a broader shift in oncology: endpoints must evolve alongside treatment paradigms. Metastases-directed therapy is not a single intervention but often part of a longitudinal strategy, where disease control may be achieved through repeated, targeted treatments. In this setting, conventional definitions of progression may inadequately reflect clinical benefit.
By adopting more tailored endpoints, future trials may become more comparable, more clinically relevant, and more aligned with patient priorities.
Conclusion
This consensus represents an important step toward refining clinical trial design in oligometastatic cancer. While overall survival remains central, integrating additional endpoints such as polymetastatic progression-free survival and systemic therapy–free survival provides a more comprehensive assessment of treatment benefit.
As the role of metastases-directed therapy continues to expand, aligning endpoints with both biology and patient experience will be essential to inform clinical practice and guide future research.
Read full article here.
Written by Aren Karapetyan, MD