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Original research
Impact of time-to-treatment on survival for advanced non-small cell lung cancer patients in the Netherlands: a nationwide observational cohort study
  1. Sosse E Klarenbeek1,
  2. Mieke J Aarts2,
  3. Michel M van den Heuvel3,
  4. Mathias Prokop1,
  5. Marcia Tummers4,
  6. Olga C J Schuurbiers3
  1. 1Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands
  2. 2Research and Development, Dutch Association of Comprehensive Cancer Centres, Utrecht, The Netherlands
  3. 3Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
  4. 4Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands
  1. Correspondence to Sosse E Klarenbeek, Department of Medical Imaging, Radboudumc, Nijmegen 6500 HB, Gelderland, The Netherlands; sosse.klarenbeek{at}


Background The assumption that more rapid treatment improves survival of advanced non-small cell lung cancer (NSCLC) has not yet been proven. We studied the relation between time-to-treatment and survival in advanced stage NSCLC patients in a large multicentric nationwide retrospective cohort. Additionally, we identified factors associated with delay.

Method We selected 10 306 patients, diagnosed and treated between 2014 and 2019 for clinical stage III and IV NSCLC, from the Netherlands Cancer Registry that includes nationwide data from 109 Dutch hospitals. Associations between survival and time-to-treatment were tested with Cox proportional hazard regression analyses. Time-to-treatment was adjusted for multiple covariates including diagnostic procedures and type of therapy. Factors associated with delay were identified by multilevel logistic regression.

Results Risk of death significantly decreased with longer time-to-treatment for stage III patients receiving only radiotherapy (adjusted HR, aHR >21 days: 0.59 (95% CI 0.48 to 0.73)) or any type of systemic therapy (aHR >49 days: 0.72 (95% CI 0.56 to 0.91)) and stage IV patients receiving chemotherapy and/or immunotherapy (aHR >21 days: 0.81 (95% CI 0.73 to 0.88)). No significant association was found for stage III patients treated with chemoradiotherapy and stage IV patients treated with targeted therapy. More complex diagnostic procedures often delay treatment.

Conclusion Although in general it is important to start treatment as early as possible, our study finds no evidence that a more rapid start of treatment improves outcomes in advanced stage NSCLC patients. The benefit of urgent treatment is probably confounded by unmeasured patient and tumour characteristics and, clinical urgency dictating timelines of treatment. Time-to-treatment and its impact should be continuously evaluated as therapeutic strategies continue to evolve and improve.

  • Non-Small Cell Lung Cancer
  • Clinical Epidemiology
  • Lung Cancer

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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  • Contributors Conceptualisation: MP, OCJS, MMvdH, MJA and SEK. Methodology: MP, OCJS, MJA and SEK. Formal analysis and Interpretation: MJA and SEK. Writing-original draft preparation: OCJS, MT, MJA and SEK. Writing-review and editing: MP, OCJS, MMvdH, MJA, MT and SEK. Supervision: MP, OCJS, MMvdH and MT. Project administration: SEK. Guarantor: OCJS.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests Outside the submitted work MJA has received a research grant from Amgen (paid to the institution).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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