Physical functioning of patients undergoing neoadjuvant treatment for cancer of the oesophagus and the subsequent impact of exercise prehabilitation—results of a cohort study within the PREHIIT trial

Background: Multimodality treatment {surgery + pre-operative chemoradiation [chemoradiotherapy for oesophageal cancer followed by surgery (CROSS)] or perioperative chemotherapy [fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT)]} is the standard of care for locally advanced oesophageal cancer. Whilst highly tolerated, clinically, patients may experience toxicities which negatively impact their functional status. Exercise prehabilitation aims to improve functional status in advance of oesophagectomy to minimise postoperative morbidities. The PRE-HIIT trial examined the ability of a high-intensity interval training (HIIT) exercise programme to improve cardiorespiratory fitness in advance of complex cancer surgery. This cohort study charts the physical functioning of a sub-cohort of participants recruited at the point of oesophageal cancer diagnosis to the PRE-HIIT trial and examines the impact of neoadjuvant treatment and subsequent exercise prehabilitation on these measures. Methods: Patients with a confirmed diagnosis of oesophageal cancer, scheduled for pre-operative chemoradiation or perioperative chemotherapy, who were free from co-morbidity which would preclude cardiopulmonary exercise test (CPET) completion, were recruited from the Upper Gastrointestinal Cancer Clinic at St James’s Hospital, Dublin. As per the Functional Ability Framework, participants completed a comprehensive physical function assessment battery inclusive of physical parameters [CPET (peak power), leg press 1-repetition maximum (1-RM)], function [short physical performance battery (SPPB)], and activity goals {self-reported physical activity levels [International Physical Activity Questionnaire (IPAQ)]}. Measures were completed at diagnosis of oesophageal cancer (T0), post-neoadjuvant treatment (T1), and post-prehabilitation (T2). Following completion of the T1 assessment, participants were randomised to complete either HIIT or standard of care (referral to moderate intensity exercise prehabilitation). Results: From June 2021 to September 2023, fourteen patients with a confirmed diagnosis of oesophageal cancer and scheduled for neoadjuvant treatment [CROSS (n=9), FLOT (n=5)] were recruited. Participants were a mean [standard deviation (SD)] 63.29 (7.28) years old and mostly male (n=9). The physical parameter of peak power was sub-optimal in this cohort, with only 1 (7.14%) achieving normative values at T0, none at T1, and 2/8 (25%) at T2. Significant changes in peak power from T0 to T2 were observed (P=0.004, η_p² =0.547). The physical parameter muscle strength (leg press 1-RM) (P=0.40,η_p² =0.143) and function (SPPB) (P=0.27, W=0.163) remained stable across the three time points. In terms of activity goals, significant changes in self-reported total leisure (P=0.045, W=0.388), total vigorous (P=0.001, W=0.851) and total physical activity were observed from T0 to T2 with post-hoc testing demonstrating significant difference between T0 and T1 for both total vigorous (P=0.001, effect size =1.28) and total physical activity (P=0.04, effect size =0.89). Conclusions: Cardiorespiratory fitness (peak power), a validated predictor of post-operative outcomes, was sub-optimal in this cohort. In addition, a significant decline in physical activity engagement was observed post-neoadjuvant treatment, highlighting the need for interventions to mitigate this. Further randomised controlled trials are required to determine the optimum parameters for exercise prehabilitation for those undergoing multimodality treatment for cancer of the oesophagus.