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

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. This Review outlines the multifaceted influence of obesity on cancer treatment effectiveness and associated toxicities, and explores complex issues, such as body composition and the obesity paradox, that link obesity with outcomes for patients with cancer.