Locally Advanced Non-small Cell Lung Cancer (NSCLC)
Conditions
Keywords
Non-small cell lung cancer, Locally advanced NSCLC, Neoadjuvant therapy, Immunotherapy, Prehabilitation, Exercise training, VO2peak, Cardiopulmonary exercise testing, Thoracic surgery, Postoperative complications
Brief summary
The PREHAB study focuses on patients with locally advanced non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemotherapy and/or immunotherapy prior to surgical resection. These systemic treatments frequently impair patients' physiological reserve, reduce physical fitness, and may occasionally lead to cancellation of surgery. Surgery itself carries a substantial risk of cardiorespiratory complications and long-term functional decline. The primary objective of this study is to determine whether a supervised exercise program, initiated concomitantly with systemic therapy and continued until surgery, can improve cardiorespiratory fitness, surgical tolerance, and postoperative outcomes. A total of 74 patients will be randomly assigned to one of two groups: an "intervention" group participating in three weekly sessions of supervised endurance and resistance training for 12 to 16 weeks under the guidance of a physiotherapist, and a "control" group receiving usual care without a structured exercise program. The primary endpoint will be peak oxygen uptake (VO₂peak). Secondary outcomes will include postoperative complication rates, length of hospital stay, pulmonary function, skeletal muscle mass, and quality of life. Intervention-related risks, primarily falls or overexertion, will be mitigated through professional supervision. This multicenter study, with recruitment scheduled to begin in 2026, is expected to provide robust evidence regarding the effectiveness of targeted exercise training in improving preoperative fitness and postoperative recovery in patients with locally advanced NSCLC.
Detailed description
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.
Interventions
PROCEDUREPreoperative Exercise Training
The intervention consists of a structured, supervised pre-operative exercise training program initiated concomitantly with induction chemo- and/or immunotherapy and continued until 24-72 hours prior to surgery. The program is delivered in an outpatient setting and supervised by trained physiotherapists following a standardized protocol across study sites. Participants randomized to the intervention group will complete three sessions per week, each lasting 45-60 minutes, for a total duration of 12 to 16 weeks depending on the length of induction therapy. Each session combines aerobic and resistance training components. Aerobic exercise is performed on a cycle ergometer at an initial intensity of approximately 60% of baseline VO₂peak, with progressive increases in duration and intensity aiming for 30-40 minutes at a Borg perceived exertion score of 4-6. Resistance training targets major upper and lower muscle groups using functional exercises.
Sponsors
Hôpital du Valais
University Hospital, Geneva
Centre Hospitalier Universitaire Vaudois
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in peak oxygen uptake (VO₂peak) from baseline to pre-surgery | From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks. | The primary endpoint is peak oxygen uptake (VO₂peak), measured by standardized cardiopulmonary exercise testing (CPET). VO₂peak reflects the integrative capacity of the cardiovascular, pulmonary, and muscular systems during maximal exertion and is a validated indicator of surgical fitness and perioperative risk. VO₂peak will be assessed at baseline (before induction therapy) and repeated 24-72 hours prior to surgery. The primary analysis will compare pre-surgery VO₂peak between groups using ANCOVA adjusted for baseline VO₂peak. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in ventilatory efficiency (VE/VCO₂ slope) from baseline to pre-surgery | From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks. | VE/VCO₂ slope measured during CPET as an index of ventilatory efficiency and ventilation-perfusion matching. Elevated values are associated with increased perioperative risk. The outcome is the between-group difference at pre-surgery adjusted for baseline value. |
| Change in 6-minute walk distance from baseline to pre-surgery | From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks. | Distance walked during the standardized 6-minute walk test (6MWT) performed indoors on a 30-meter corridor according to established guidelines. The outcome is the between-group difference in walking distance at pre-surgery adjusted for baseline. |
| Rate of 30-day postoperative cardiopulmonary complications | From surgery to 30 days postoperatively. | Proportion of patients experiencing at least one predefined cardiopulmonary complication within 30 days after surgery, including atrial fibrillation, pneumonia, prolonged air leak, pulmonary embolism, ARDS, pneumothorax, or myocardial infarction. Between-group comparison. |
| Length of postoperative hospital stay | From surgery until hospital discharge. | Number of days from the date of surgery to hospital discharge. Comparison of mean length of stay between intervention and control groups. |
| Change in health-related quality of life (EORTC QLQ-C30 global score) | From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks. | Health-related quality of life assessed using the EORTC QLQ-C30 questionnaire (version 3.0). The primary QoL endpoint is the global health status/quality of life score. Between-group comparison of change from baseline to pre-surgery. |
| Change in skeletal muscle cross-sectional area on CT imaging | From baseline to 4-6 weeks prior to surgery at approximately 12 weeks. | Skeletal muscle cross-sectional area and radiodensity measured on CT scans at the L3 vertebral level. Change from baseline to pre-surgery compared between groups as an index of sarcopenia and muscle quality. |
| Change in pulmonary function (FEV1 and DLCO) from baseline to pre-surgery | From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks. | Forced expiratory volume in 1 second (FEV1) and diffusing capacity for carbon monoxide (DLCO) measured using standardized pulmonary function testing. Between-group comparison of change from baseline to pre-surgery. |
Countries
Switzerland
Outcome results
None listed