Precision Exercise Effect on Fatigue and Function in Lung Cancer Surgery
Authors: Cornelia M. Ulrich, Caroline Himbert, Christopher A. Barnes, Kenneth M. Boucher, Bailee Daniels, Victoria M. Bandera, Jennifer A. Ligibel, David W. Wetter, Rachel Hess, Jaewhan Kim, Kelly Lundberg, Brian Mitzman, Robin Marcus, Samuel R. G. Finlayson, Paul C. LaStayo, Thomas K. Varghese
Journal: JAMA Surgery (2025)

Importance Exercise intervention studies have shown benefits for patients with lung cancer undergoing surgery, yet most interventions to date have been resource intensive and have followed a one-size-fits-all approach. Objective To determine whether a personalized, clinic-aligned perioperative exercise program with remote monitoring and instructions can improve physical function and fatigue among patients undergoing surgery for lung cancer. Design, Setting, and Participants The Precision-Exercise-Prescription (PEP) randomized clinical trial is a single-center phase 3 trial. Adult patients with primary lung cancer (stages I-IIIa) or oligometastatic disease to the lung (where all disease could be removed) were assessed for eligibility and randomized to either an exercise intervention or standard care. Patients were enrolled between November 2017 and 2021, and the trial continued during the COVID-19 pandemic. Data were analyzed from November 2022 to December 2023. Interventions The structured exercise program, personalized based on mobility scores, was a home-based exercise intervention prescribed and monitored remotely by a licensed physical therapist. The program started approximately 2 weeks before surgery and continued after surgery. Standard care included use of incentive spirometer and encouragement to exercise without a formal program. Main Outcomes and Measures Physical function (6-minute walk test [6MWT]), the Short Physical Performance Battery, and cancer-related fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue) were assessed at baseline and 2 months after surgery. Results A total of 182 patients (92 receiving exercise intervention, 90 receiving standard care) were assessed in the intention-to-treat population. Patients had a mean (SD) age of 62.7 (13.8) years, 108 (59%) were female, and 89 (49%) had low mobility scores (Activity Measure for Post-Acute Care scores, 1-3). Physical function in the exercise group increased at 2 months after surgery (mean [SE] 6MWT at baseline, 467.9 [13.0] m; at 2 months, 482.2 [14.1] m), compared with a decrease in the standard-care group (mean [SE] 6MWT at baseline, 481.4 [11.1] m; at 2 months, 471.5 [14.0] m). Mean (SE) between-group changes in 6MWT distance for intent to treat from baseline to 2 months were 22.7 (12.7) m ( P = .08), with greater effect sizes among women (mean [SE], 37.8 [17.3] m; P = .03). Similarly, women showed greater improvements in the Short Physical Performance Battery (mean [SE], 0.9 [0.4]; P = .04). Patients in the exercise group maintained stable fatigue scores at 2 months, whereas participants in the standard-care group deteriorated (mean [SD], 3.7 [1.4]; P = .009), with greater effect sizes among individuals who were younger, from rural areas, had overweight or obesity, and had primary lung cancer. Conclusions and Relevance The PEP intervention, a personalized, clinic-aligned, and remotely monitored perioperative exercise program for patients with lung cancer undergoing surgery demonstrated improvements in physical function for women and significant improvements in fatigue scores across all groups. Trial Registration ClinicalTrials.gov Identifier: NCT03306992