Exercise prehabilitation may lead to augmented tumor regression following neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Abstract

 

Purpose: We evaluate the effect of an exercised prehabilitation programme on tumour response in rectal cancer patients following neoadjuvant chemoradiotherapy (NACRT).

Patients and Methods: Rectal cancer patients with (MRI-defined) threatened resection margins who completed standardized NACRT were prospectively studied in a post hoc, explorative analysis of two previously reported clinical trials. MRI was performed at Weeks 9 and 14 post-NACRT, with surgery at Week 15. Patients undertook a 6-week preoperative exercise-training programme. Oxygen uptake (VO2) at anaerobic threshold (AT) wasmeasured at baseline (pre-NACRT), after completion of NACRT and at week 6 (post-NACRT). Tumour related outcome variables: MRI tumour regression grading (ymrTRG) at Week 9 and 14; histopathological T-stage (ypT); and tumour regression grading (ypTRG)) were compared.

Results: 35 patients (26 males) were recruited. 26 patients undertook tailored exercise-training with 9 unmatched controls. NACRT resulted in a fall in VO2 at AT −2.0 ml/kg⁻¹/min⁻¹(−1.3,−2.6), p < 0.001. Exercise was shown to reverse this effect. VO2 at AT increased between groups, (post-NACRT vs. week 6) by +1.9 ml/kg⁻¹/min⁻¹(0.6, 3.2), p = 0.007. A significantly greater ypTRG in the exercise group at the time of surgery was found (p = 0.02).

Conclusion: Following completion of NACRT, exercise resulted in significant improvements in fitness and augmented pathological tumour regression.

Trial registration: ClinicalTrials.gov identifier: NCT01325909.

Trial registration: ClinicalTrials.gov identifier: NCT01859442.

Acknowledgment

Special thanks go to Dr Monica Terlizzo, Consultant Histopathologist, for histopathological analysis.

Disclosure statement

All authors confirm that they have no disclosures or conflicts of interest pertaining to this study.

Additional information

Funding

This work was undertaken while MW and MPWG were funded by the National Institute of Health Research and the Royal College of Anaesthetists British Oxygen Company Fellowship awarded by the National Institute of Academic Anaesthesia for the Fit-4-Surgery program of research, Aintree University Hospitals NHS Foundation Trust, Liverpool, Colorectal Multi-Disciplinary Team. MW, HM, DZHL, JC, MPWG and SJ are partly supported by the Southampton NIHR Biomedical Research Centre at University Hospital Southampton NHS Foundation Trust. RA is partly supported by the NIHR Biomedical Research Centre at University College London Hospitals. Funders and study sponsors had no role in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.