Clinical trial endpoints for metastases-directed therapy in oligometastatic cancer: a review and Delphi consensus on behalf of the EORTC–ESTRO OligoCare consortium

Widder J, Bol GM, Simek IM, Ehret F, Abdel-Aty H, Basic S, Chuter D, Daly J, Fairbrother P, Zeqa D, Aboubakar Nana F, Achard V, Corradini S, Correia D, De Ruysscher D, Dingemans AMC, Faivre-Finn C, Gillessen S, Guren MG, Hendriks L, Kunz WG, Lecouvet FE, Levy A, Lievens Y, McDonald F, Meattini I, Oppong F, Oprea-Lager D, Palma D, Fredberg Persson G, Remon J, Vandemaele M, van Laarhoven HW, Verkooijen HM, Visani L, Zilli T, Ost P, Guckenberger M (2026)

Publication Type: Journal article, Review article

Publication year: 2026

Journal

Book Volume: 27

Pages Range: e238-e247

Journal Issue: 5

DOI: 10.1016/S1470-2045(26)00075-6

Abstract

Oligometastatic cancer is characterised by a low volume of metastases to a small number of anatomical sites. However, evaluating the impact of metastases-directed therapies (MDTs) on overall survival or quality of life is often challenging. Current clinical trials use a wide range of primary endpoints that might not be validated or suited to MDT. To address this issue, we did a systematic review of international trial registries, alongside a Delphi consensus process involving 30 experts and five patient representatives. The aim was to identify preferred primary endpoints for MDT trials in oligometastatic disease, regardless of tumour type. Overall survival and progression-free survival were the most frequently used endpoints across the 121 comparative trials reviewed. Over four Delphi consensus rounds, overall survival had the highest level of agreement, although its limitations as a sole endpoint were emphasised. In addition to the widely used progression-free survival endpoint, polymetastatic progression-free survival and start-or-switch of systemic therapy-free survival also reached consensus, particularly for trials integrating systemic therapies. Both polymetastatic progression-free survival and systemic therapy-free survival permit repeat MDT without classifying it as treatment failure. Patient representatives highlighted the importance of time-to-deterioration of quality of life. This consensus supports overall survival as a primary endpoint and, in addition to progression-free survival, recommends polymetastatic progression-free survival and systemic therapy-free survival, especially in combination with systemic therapies. Adopting these endpoints will make MDT trials more relevant, comparable, and patient-centred, thereby empowering future clinical and policy decisions.

Authors with CRIS profile

Involved external institutions

Universiteit Gent (UGent) / Ghent University Belgium (BE) Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra Netherlands (NL) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL) Careggi University Hospital / Azienda Ospedaliero Universitaria Careggi Italy (IT) Geneva University Hospitals / Hôpitaux universitaires de Genève (HUG) Switzerland (CH) Universitätsspital Zürich (USZ) Switzerland (CH) Independent Cancer Patients' Voice (ICPV) United Kingdom (GB) Europa Donna Albania - The European Breast Cancer Coalition Albania (AL) de Duve Institute Belgium (BE) Institut Gustave-Roussy France (FR) University Hospital Ghent Belgium (BE) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) Maastricht University Medical Center (UMC+) Netherlands (NL) European Organisation for Research and Treatment of Cancer (EORTC) Belgium (BE) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) Netherlands (NL) Western University Canada (CA) Gentofte Hospital Denmark (DK) Institut Bergonié France (FR) Kantonsspital Aarau AG Switzerland (CH) Erasmus University Medical Center (MC) Netherlands (NL) University of Manchester United Kingdom (GB) Oncology Institute of Southern Switzerland / Istituto Oncologico della Svizzera Italiana Switzerland (CH) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Klinikum der Universität München (LMU Klinikum) Germany (DE) Cliniques universitaires Saint-Luc (CHU St-Luc) Belgium (BE) Medizinische Universität Wien Austria (AT) Allergan Pharmaceuticals, Inc. United States (USA) (US) Charité - Universitätsmedizin Berlin Germany (DE) EGM Cancer Support Ireland (IE)

How to cite

APA:

Widder, J., Bol, G.M., Simek, I.M., Ehret, F., Abdel-Aty, H., Basic, S.,... Guckenberger, M. (2026). Clinical trial endpoints for metastases-directed therapy in oligometastatic cancer: a review and Delphi consensus on behalf of the EORTC–ESTRO OligoCare consortium. Lancet Oncology, 27(5), e238-e247. https://doi.org/10.1016/S1470-2045(26)00075-6

MLA:

Widder, Joachim, et al. "Clinical trial endpoints for metastases-directed therapy in oligometastatic cancer: a review and Delphi consensus on behalf of the EORTC–ESTRO OligoCare consortium." Lancet Oncology 27.5 (2026): e238-e247.

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