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Clinical Studies

Association between effectiveness of treatment with curative intent and outcomes of first-line systemic therapy in metachronous metastatic gastroesophageal adenocarcinoma

British Journal of Cancer (2026)Cite this article

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Abstract

Background

Almost half of the patients with gastroesophageal cancer treated with curative intent develop recurrence. It is unknown whether the effectiveness of curative treatment is associated with the outcomes of subsequent first-line systemic therapy.

Methods

From the Netherlands Cancer Registry, we identified patients with metachronous metastatic gastroesophageal adenocarcinoma(mGEA) initially treated for nonmetastatic disease(2015–2017) with perioperative chemotherapy or neoadjuvant chemoradiotherapy, who later received first-line systemic therapy. Effectiveness of the treatment with curative intent was assessed by time-to-treatment-failure(TTF) and by pathological response. First-line systemic therapy outcomes were assessed by TTF and overall survival(OS). Associations were analysed using Kaplan–Meier curves and multivariable Cox models.

Results

Patients treated with perioperative chemotherapy (n = 81) and neoadjuvant chemoradiotherapy (n = 249) with a TTF longer than the median (19.6 and 14.9 months, respectively) had significantly longer first-line TTF(HR 1.94 95% CI: 1.18–3.19; HR 1.36, 95%CI: 1.04–1.78). This also translated into longer OS for neoadjuvant chemoradiotherapy (HR 1.35 95% CI 1.03–1.77). Pathological response was not associated with systemic therapy outcomes.

Conclusions

A longer TTF of curative treatment was positively associated with improved first-line systemic therapy outcomes in patients with metachronous mGEA. When counselling patients, TTF of their curative treatment may be considered, whereas pathological response may not.

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Fig. 1
Fig. 2
Fig. 3: Kaplan–Meier curves of outcomes of first-line systemic therapy in patients treated with perioperative chemotherapy.
Fig. 4: Kaplan–Meier curves of outcomes of first-line systemic therapy in patients treated with neoadjuvant chemoradiotherapy.

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Data availability

Data can be made available by the Netherlands Comprehensive Cancer Organisation on justified request.

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Acknowledgements

The authors acknowledge the use of ChatGPT (OpenAI) to improve the readability and clarity of the manuscript. No text was generated or copied directly from the tool; all scientific content and wording were conceived and written by the authors.

Funding

This work was financially supported by UMC Utrecht & Wilhelmina Kinderziekenhuis Foundation [project number 1522166]. The funder was not involved in the study design, collection, analysis and interpretation of data, writing of the report or the decision to submit the article for publication.

Author information

Authors and Affiliations

  1. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    D. Kamp & A. M. May

  2. Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands

    A. M. May

  3. Department of Medical Oncology, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands

    M. J. M. van Velzen, R. H. A. Verhoeven & H. W. M. van Laarhoven

  4. Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands

    M. J. M. van Velzen, R. H. A. Verhoeven & H. W. M. van Laarhoven

  5. Department of Radiotherapy, Imaging and Cancer, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

    S. Mook

  6. Department of Pathology, Imaging and Cancer, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

    J. E. Freund

  7. Department of Medical Oncology, Erasmus MC Cancer Institute University Medical Center Rotterdam, Rotterdam, the Netherlands

    B. Mostert

  8. Department of Research & Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands

    R. H. A. Verhoeven

  9. Department of Medical Oncology, Imaging and Cancer, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

    N. Haj Mohammad

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Contributions

DK: writing—original draft, investigation, formal analysis, data curation, methodology. AMM: writing—review & editing, supervision, methodology, investigation. HWMvL: writing—review & editing, supervision, methodology, investigation, conceptualisation. NHM: writing—review & editing, supervision, methodology, investigation, conceptualisation, resources. MJMvV: writing—review & editing, conceptualisation, investigation. SM, JEF, BM, RHAV: writing—review & editing, investigation

Corresponding author

Correspondence to N. Haj Mohammad.

Ethics declarations

Competing interests

HWMvL has acted as a consultant or in an advisory role for Auristone, Incyte, Merck, Myeloid, Servier; and has received research funding and/or medication/material supply from Amphera, Anocca, Astellas, AstraZeneca, Beigene, Boehringer, BMS, Daiichy-Sankyo, Dragonfly, MSD, MyeloidTx, ORCA, Servier and speaker roles for Astellas, Beigene, Benecke, BMS, Daiichy-Sankyo, JAAP, Medtalks, Novartis, Springer, Travel Congress Management B.V, and has received travel support from AstraZeneca. NHM has acted as a consultant or in an advisory role for BMS, Astra Zeneca, Servier, MSD, and Eli Lilly; and has received research funding and/or medication/material supply from Servier. RHAV has received research funding from BMS and Amgen and has acted as consultant for Daiichi Sankyo. BM: has received research funding and/or medication supply from BMS and Pfizer; and has acted as a consultant or in an advisory role for Amgen. AMM, MJMvV, SM, JEF and DK declare no conflicts of interest.

Ethics approval

This study did not require approval from an Institutional Review Board in the Netherlands, as determined by the Central Committee on Research Involving Human Subjects. However, it was approved by the Privacy Review Board of the Netherlands Cancer Registry (request number K19.288) and the scientific committee of the Dutch Upper GI Cancer Group. The study was approved in accordance with the Declaration of Helsinki.

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Kamp, D., May, A.M., van Velzen, M.J.M. et al. Association between effectiveness of treatment with curative intent and outcomes of first-line systemic therapy in metachronous metastatic gastroesophageal adenocarcinoma. Br J Cancer (2026). https://doi.org/10.1038/s41416-026-03374-5

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