Multimodal prehabilitation to prevent loss of cardiorespiratory fitness in patients with locally advanced lung cancer undergoing chemoimmunotherapy: protocol for a non-randomized multicentre study

Background: Non-small cell lung cancer (NSCLC) is the second most common cancer globally and a leading cause of cancer-related mortality. Although 5-year survival rates remain lower than those of other cancer types, significant improvements have been observed in recent years, largely due to the introduction of immunotherapy and targeted therapies. Recently, immune checkpoint inhibitors (ICIs) have been approved for use in combination with standard double-platinum chemotherapy in the neoadjuvant setting for resectable NSCLC, improving outcomes and extending time to recurrence. However, neoadjuvant therapy (NAT) can lead to declines in pulmonary function and cardiorespiratory fitness (CRF), thereby increasing the risk of postoperative complications. This study aims to evaluate the effects of multimodal prehabilitation on maintaining CRF and enhancing surgical resilience in patients with NSCLC undergoing neoadjuvant chemoimmunotherapy. Methods: Ambispective cohort study to evaluate the feasibility and preliminary efficacy of multimodal prehabilitation in patients with NSCLC undergoing NAT with chemoimmunotherapy. Eligible patients will be recruited from tertiary cancer centres in Spain and France. The intervention will include: (I) a supervised exercise training conducted twice weekly through the duration of NAT until surgery; (II) a nutritional assessment with a personalized dietary plan; and (III) psychological support. Additional services (such as smoking cessation counselling) will be provided if needed. The primary outcome will be changes in peak oxygen uptake (VO2peak), measured via cardiopulmonary exercise test (CPET) before and after NAT. Secondary outcomes will include: (I) feasibility (recruitment rate, treatment completion rate, adherence and training compliance); (II) functional capacity; (III) mood; (IV) treatment-related toxicity and adverse events; (V) postoperative outcomes (complications and length of hospital stay); and (VI) postoperative recovery of functional capacity. Discussion: This trial aims to provide data on efficacy, safety, and feasibility to support the implementation of prehabilitation for patients with resectable NSCLC undergoing NAT. Trial Registration: ClinicalTrials.gov; NCT05636969.