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The multifactorial effect of obesity on the effectiveness and outcomes of cancer therapies

Nature Reviews Endocrinology (2024)Cite this article

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Abstract

Epidemiology studies have demonstrated a clear association between obesity and the development of several distinct malignancies, with excessive visceral adiposity being an increasingly prevalent feature in patients with cancer presenting for therapeutic intervention. Clinical trials and meta-analyses have helped to inform effective and safe dosing of traditional systemically administered anticancer agents in adult patients with cancer and obesity, but there remains much debate not only regarding the effect of obesity on the more novel targeted molecular and immune-based therapies, but also about how obesity is best defined and measured clinically. Low muscle mass is associated with poor outcomes in cancer, and body composition studies using biochemical and imaging modalities are helping to fully delineate the importance of both obesity and sarcopenia in clinical outcomes; such studies might also go some way to explaining how obesity can paradoxically be associated with favourable clinical outcomes in certain cancers. As the cancer survivorship period increases and the duration of anticancer treatment lengthens, this Review highlights the challenges facing appropriate treatment selection and emphasizes how a multidisciplinary approach is warranted to manage weight and skeletal muscle loss during and after cancer treatment.

Key points

  • Obesity drives pathological inflammation and simultaneously disrupts ongoing antitumour immune responses.

  • Patients with overweight or obesity and low muscle mass experience more surgical complications, treatment-related toxicities, a higher risk of recurrence and cancer-specific mortality than patients with a BMI in the normal range.

  • Research into dose optimization in patients with cancer and obesity is required, focusing on how body composition and BMI can affect drug distribution, dosing and toxicities.

  • Both muscle mass and quality are important factors to consider when assessing the functional influence of sarcopenia and obesity on toxicities and outcomes following cancer treatment.

  • During cancer treatment, patients with cancer can experience unintentional muscle loss owing to factors including treatment adverse effects, changes in food taste and changes in lifestyle.

  • The interplay of obesity with sex, psychosocial and socioeconomic factors influences access to cancer screening, diagnosis and treatments, ultimately affecting outcomes.

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Fig. 1: Obesity-associated cancers, relative risk, treatment efficacy, toxicities and outcomes.
Fig. 2: Increased visceral adiposity influences tumour growth at distal sites.
Fig. 3: The BMI paradox in patients with cancer.
Fig. 4: Weight management after cancer treatment.

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Authors and Affiliations

  1. Cancer Immunology and Immunotherapy Group, Department of Surgery, School of Medicine, Trinity Translational Medicine Institute and Trinity St. James’s Cancer Institute, Trinity College Dublin, St James’s Hospital, Dublin, Ireland

    Joanne Lysaght

  2. Cancer Immunology Research Group, Department of Anatomy, School of Medicine, Trinity Biomedical Sciences Institute and Trinity St. James’s Cancer Institute, Trinity College Dublin, Dublin, Ireland

    Melissa J. Conroy

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Lysaght, J., Conroy, M.J. The multifactorial effect of obesity on the effectiveness and outcomes of cancer therapies. Nat Rev Endocrinol (2024). https://doi.org/10.1038/s41574-024-01032-5

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