Effect of Pre-operative Exercise Training on Cardiorespiratory Fitness in Patients With Locally Advanced Non-small Cell Lung Cancer Undergoing Induction Chemo-immunotherapy Followed by Surgery - a Randomized Controlled Study

The PREHAB study is a prospective, multicenter, randomized controlled trial designed to evaluate the efficacy of a structured, supervised prehabilitation program in patients with locally advanced non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemotherapy and/or immunotherapy prior to surgical resection.

Patients with stage III NSCLC increasingly receive multimodal treatment strategies combining systemic therapy followed by surgery. While neoadjuvant chemotherapy and immunotherapy have improved oncologic outcomes, these treatments frequently induce treatment-related deconditioning, sarcopenia, fatigue, and reduced cardiopulmonary reserve. Consequently, a subset of patients experiences functional decline significant enough to compromise surgical eligibility. Moreover, thoracic surgery itself is associated with substantial postoperative morbidity, particularly cardiorespiratory complications, and long-term impairment in physical performance.

The PREHAB trial is based on the hypothesis that early, structured, and supervised exercise training initiated concomitantly with systemic therapy and continued until surgery can mitigate treatment-induced physiological deterioration, preserve or enhance cardiorespiratory fitness, and ultimately improve perioperative and postoperative outcomes.

A total of 74 patients will be randomized in a 1:1 ratio to either:

• Intervention group: participation in a 12-16 week supervised exercise program consisting of three weekly sessions combining endurance and resistance training, delivered by trained physiotherapists.
• Control group: standard oncologic care without a structured exercise intervention.

The primary endpoint is change in peak oxygen uptake (VO₂peak), measured by cardiopulmonary exercise testing, as an objective marker of cardiorespiratory fitness and surgical resilience.

Secondary endpoints include:

• Postoperative complication rates
• Length of hospital stay
• Pulmonary function parameters
• Skeletal muscle mass
• Health-related quality of life

Safety considerations focus primarily on the risk of falls and overexertion, both minimized through professional supervision and individualized exercise prescription.

By targeting the vulnerable neoadjuvant window - when patients are exposed to systemic therapy but have not yet undergone surgery - PREHAB aims to redefine perioperative optimization in locally advanced NSCLC. If positive, this trial could provide high-level evidence supporting the integration of structured exercise prehabilitation into standard multimodal lung cancer care pathways.

Inclusion criteria

• Age ≥18 years.
• Confirmed diagnosis of stage IIB, IIIA, IIIB or oligo-metastatic stage IV NSCLC.
• Planned induction therapy with either chemotherapy, immunotherapy or a combination of immuno-chemotherapy followed by an anatomical pulmonary resection.
• Absence of musculoskeletal conditions preventing safe physical exercise.
• Absence of any history of uncontrolled or unstable cardiac disease.
• Agreement to participate in the study by signing the study specific informed consent form.

Exclusion criteria

• Pregnancy (confirmed by a test if applicable).
• Induction therapy already initiated.
• Inability to walk independently.
• Lack of decision-making capacity.
• Oxygen-dependency before the initiation of the induction protocol.
• No capacity for discernment.
• Does not speak French.