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Lung metastases

Nature Reviews Disease Primers volume 11, Article number: 60 (2025) Cite this article

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Abstract

Up to 50% of patients with metastatic cancer develop lung metastases during their disease course. Lung metastases are linked to poor prognosis across various cancer types and might impair the quality of life of patients, causing dyspnoea, cough, haemoptysis and pain, potentially diminishing physical, functional and emotional well-being. Lung metastases arise from a complex interplay of tumour-secreted factors such as VEGF, TGFβ and CCL2, which drive vascular remodelling, immune cell recruitment and extracellular matrix reprogramming. Additionally, tumour-derived exosomes and microparticles contribute to organotropism and immunosuppression by altering the lung microenvironment. The ensemble of these modifications creates a pre-metastatic niche conducive to tumour cell colonization and outgrowth. Lung metastases are primarily diagnosed through imaging; histological confirmation is sometimes required to distinguish them from primary lung cancer. The size and number of lung metastases, timing of primary cancer treatment, histology, and the patient’s clinical condition are all considered to determine the most appropriate treatment. When a locoregional approach is not possible, histology-based, molecular-driven systemic therapy is the choice. No systemic treatment is currently available specifically for lung metastases. Advances in understanding the distinct stages of pre-metastatic niche formation and lung metastasis outgrowth might lead to the development of prevention strategies and tailored treatments.

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Fig. 1: Common primary tumours that metastasize to the lung.
Fig. 2: Establishment of the pulmonary pre-metastatic niche.
Fig. 3: Tumour–microenvironment interplay in establishment and maintenance of the pre-metastatic niche.
Fig. 4: Radiological appearance of lung metastases and primary lung tumour.
Fig. 5: Histology of lung metastasis of different primary tumours.

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Authors and Affiliations

  1. Cancer Medicine Department, Gustave Roussy, Villejuif, France

    Lodovica Zullo & Benjamin Besse

  2. Department of Experimental Medicine, University of Genova, Genova, Italy

    Lodovica Zullo

  3. 2nd Department of Radiology, University General Hospital “Attikon” Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Dimitris Filippiadis

  4. Department of Pulmonary Diseases, GROW – Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands

    Lizza E. L. Hendriks

  5. European Organisation for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium

    Daniel Portik

  6. Department of Radiation Oncology (Maastro), GROW – Research Institute for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands

    Daniel Portik

  7. Department of Surgery, Faculty of Medicine and Health Sciences, McGill University, Montréal, Quebec, Canada

    Jonathan D. Spicer

  8. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ignacio I. Wistuba

  9. Paris-Saclay University, Orsay, France

    Benjamin Besse

Authors
  1. Lodovica Zullo
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  2. Dimitris Filippiadis
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  3. Lizza E. L. Hendriks
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  4. Daniel Portik
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  5. Jonathan D. Spicer
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  6. Ignacio I. Wistuba
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  7. Benjamin Besse
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Contributions

Introduction (L.Z.); Epidemiology (L.E.L.H.); Mechanisms/pathophysiology (L.Z.); Diagnosis, screening and prevention (L.Z., D.F. and I.I.W.); Management (D.F., D.P., J.D.S. and L.Z.); Quality of life (L.Z.); Outlook (L.Z. and L.E.L.H.); overview of the Primer (L.Z. and B.B.).

Corresponding author

Correspondence to Benjamin Besse.

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Competing interests

B.B. declares advisory board participation (paid to institution): Abbvie, Biontech SE, BristolMyerSquibb, Chugai Pharmaceutical, CureVac AG, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Pharmamar, Regeneron, Sanofi Aventis, Turning Point Therapeutics; conseil (paid to institution): Abbvie, Eli Lilly, Ellipses pharma Ltd, F. Hoffmann-La Roche Ltd., Genmab, Immunocore, Janssen, MSD, Ose Immunotherapeutics, Owkin, Taiho Oncology; Steering Committee (paid to institution): AstraZeneca, Beigene, GENMAB A/S, GlaxoSmithKline, Janssen, MSD, Ose Immunotherapeutics, Pharmamar, Roche-Genentech, Sanofi, Takeda; speaker (paid to institution): Abbvie, AstraZeneca, Chugai Pharmaceutical, Daichii Sankyo, Hedera Dx, Janssen, MSD, Roche, Sanofi Aventis and Springer Healthcare Ltd., none related to this work. L.E.L.H. declares grants and/or research support (all paid to institution) from Roche, Boehringer Ingelheim, AstraZeneca, Takeda, Merck, Pfizer, Novartis and Gilead; is on the advisory boards (all to institution) of Amgen, Boehringer Ingelheim, Lilly, Novartis, Pfizer, Takeda, Merck, Janssen, Merck Sharp & Dohme (MSD), AnHeart Therapeutics, Bayer, Daiichi, Pierre Fabre, BMS, AbbVie, AstraZeneca and Summit Therapeutics; was a speaker on educational seminars or webinars for AstraZeneca, Bayer, Lilly, MSD, high5oncology, Takeda, Janssen, GlaxoSmithKline (GSK), Sanofi and Pfizer (all paid to the institution), and Medtalks, Benecke, VJOncology and Medimix (personal payment); performed local principal investigator pharma studies (all paid to institution) with AstraZeneca, GSK, Novartis, Merck, Roche, Takeda, Blueprint, Mirati, AbbVie, Gilead, MSD, Pfizer, Amgen and Boehringer Ingelheim; and was on member guideline committees in a personal capacity for Dutch guidelines on non-small cell lung cancer, brain metastases and leptomeningeal metastases (personal payment), and ESMO guidelines on non-small cell lung cancer and small cell lung cancer (unpaid). J.D.S. declares grants to the institution from AstraZeneca, MSD, Roche, BMS, CLS Therapeutics, Protalix Biotherapeutics, Pfizer and Regeneron; consulting fees from AstraZeneca, Merck, Roche, BMS, Novartis, Chemocentryx, Amgen, Protalix Biotherapeutics, Xenetic Biosciences, Regeneron, Eisai and Pfizer; payment for a speaking role from Peerview, OncLive and Medscape; support for attending meetings or travel from AstraZeneca, Merck and BMS; participating on a clinical trial safety monitoring board for AstraZeneca; and receiving equipment, materials, drugs, gifts or other services via grants to the institution from Roche, MSD, BMS and AstraZeneca. I.I.W. declares consulting or advisory roles for AstraZeneca/MedImmune, Bayer, Bristol Myers Squibb, Genentech/Roche, GlaxoSmithKline, Guardant Health, HTG Molecular Diagnostics, Merck, MSD Oncology, OncoCyte, Jansen, Novartis, Flame Inc., Regeneron and Pfizer; grants and personal fees from Genentech/Roche, Bristol Myers Squibb, AstraZeneca/MedImmune, HTG Molecular, Merck and Guardant Health; personal fees from GlaxoSmithKline and Oncocyte, Daiichi Sankyo, Roche, AstraZeneca, Regeneron, Sanofi, Pfizer and Bayer; research funding (paid to the institution) from 4D Molecular Therapeutics, Adaptimmune, Adaptive Biotechnologies, Akoya Biosciences, Amgen, Bayer, EMD Serono, Genentech, Guardant Health, HTG Molecular Diagnostics, Iovance Biotherapeutics, Johnson & Johnson, Karus Therapeutics, MedImmune, Merck, Novartis, OncoPlex Diagnostics, Pfizer, Takeda and Novartis. D.P. declares a consulting role for MVision AI. L.Z. and D.F. declare no competing interests.

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Nature Reviews Disease Primers thanks M. Reck; J. Minna; L. Sholl, who co-reviewed with I. Odintsov; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Zullo, L., Filippiadis, D., Hendriks, L.E.L. et al. Lung metastases. Nat Rev Dis Primers 11, 60 (2025). https://doi.org/10.1038/s41572-025-00642-1

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