JAMA Netw Open. 2026 Oct 1;9(10):e2640136. doi: 10.1001/jamanetworkopen.2026.40136.
ABSTRACT
IMPORTANCE: Physical deterioration and disease progression during neoadjuvant treatment can preclude tumor surgery in patients with gastroesophageal cancer. Whether preoperative exercise training can increase the probability of undergoing tumor surgery remains unknown.
OBJECTIVE: To compare exercise training with usual care on the likelihood of not undergoing tumor surgery with curative intent after neoadjuvant treatment for gastroesophageal cancer.
DESIGN, SETTING, AND PARTICIPANTS: PRESET-RCT was a single-blinded, parallel-group, 2-arm, superiority randomized clinical trial. Patients with gastroesophageal adenocarcinoma scheduled to undergo treatment with curative intent, including neoadjuvant treatment, and with no contraindication to exercise training were eligible. Participants were enrolled at University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark, from August 16, 2018, to September 23, 2022, with final follow-up on October 22, 2024. Data analysis was performed from March 2023 to May 2025.
INTERVENTION: The participants were randomized 1:1 to preoperative exercise training from diagnosis until tumor surgery or control. The intervention consisted of twice-weekly concurrent aerobic exercise and resistance training.
MAIN OUTCOMES AND MEASURES: The primary outcome was not undergoing tumor surgery with curative intent. The secondary outcomes were treatment tolerance and overall survival.
RESULTS: In total, 207 participants (73.7%) were randomized and 202 were included in the modified intention-to-treat analyses (mean [SD] age, 65.3 [8.5] years; 161 [78.9%] male; 170 [83.3%] with gastroesophageal junction cancer), with 101 randomized to each group. In the exercise group, 10 (9.9%) did not undergo tumor surgery with curative intent compared with 8 (7.9%) in the control group (odds ratio, 1.28; 95% CI, 0.48-3.38; P = .62). There were no between-group differences in permanent discontinuation of neoadjuvant treatment (odds ratio, 0.81; 95% CI, 0.38-1.72) or postoperative complications (odds ratio, 1.16; 95% CI, 0.61-2.20). The overall survival rates at 3 years for the exercise and control group were 51.0% and 65.0%, respectively (hazard ratio, 1.58; 95% CI, 1.02-2.45).
CONCLUSION AND RELEVANCE: In this randomized clinical trial, preoperative exercise training did not increase the likelihood of undergoing tumor surgery for patients with gastroesophageal cancer. The findings do not support the use of exercise training during neoadjuvant treatment to improve surgical outcomes, and further research is needed to determine its effects on long-term outcomes.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03490565.
PMID:42949746 | DOI:10.1001/jamanetworkopen.2026.40136
