The effects of cancer therapies on physical fitness before oesophagogastric cancer surgery: a prospective, blinded, multi-centre, observational, cohort study

Abstract

Background: Neoadjuvant cancer treatment is associated with improved survival following major oesophagogastric cancer surgery. The impact of neoadjuvant chemo/chemoradiotherapy on physical fitness and operative outcomes is however unclear. This study aims to investigate the impact of neoadjuvant chemo/chemoradiotherapy on fitness and post-operative mortality. Methods: Patients with oesophagogastric cancer scheduled for chemo/chemoradiotherapy and surgery were recruited to a prospective, blinded, multi-centre, observational cohort study. Primary outcomes were changes in fitness with chemo/chemoradiotherapy, measured using cardiopulmonary exercise testing and its association with mortality one-year after surgery. Patients were followed up for re-admission at 30-days, in-hospital morbidity and quality of life (exploratory outcomes). Results: In total, 384 patients were screened, 217 met the inclusion criteria, 160 consented and 159 were included (72% male, mean age 65 years). A total of 132 patients (83%) underwent chemo/chemoradiotherapy, 109 (71%) underwent chemo/chemoradiotherapy and two exercise tests, 100 (63%) completed surgery and follow-up. A significant decline in oxygen uptake at anaerobic threshold and oxygen uptake peak was observed following chemo/chemoradiotherapy: -1.25ml.kg-1.min-1 (-1.80 to -0.69) and -3.02ml.kg-1.min-1 (-3.85 to -2.20); p<0.0001). Baseline chemo/chemoradiotherapy anaerobic threshold and peak were associated with one-year mortality (HR=0.72, 95%CI 0.59 to 0.88; p=0.001 and HR=0.85, 0.76 to 0.95; p=0.005). The change in physical fitness was not associated with one-year mortality. Conclusion: Chemo/chemoradiotherapy prior to oesophagogastric cancer surgery reduced physical fitness. Lower baseline fitness was associated with reduced overall survival at one-year. Careful consideration of fitness prior to chemo/chemoradiotherapy and surgery is urgently needed.

Cardiopulmonary exercise variables and their association with postoperative morbidity and mortality after major oesophagogastric cancer surgery—a multicentre observational study

“… 17 , 23 , 24 , 26 Neoadjuvant treatment has become increasingly prevalent, 22 however, neither post-neoadjuvant treatment fitness, nor the change in fitness with neoadjuvant treatment were associated with outcomes, as previously reported by our group. 17 , 18 Although overall survival has moderately improved for oesophagogastric surgery patients as a result of the improvement in tumour regression grading with neoadjuvant treatment, the reduction in perioperative fitness and increased postoperative mortality needs to be acknowledged during shared decision-making. 37 In some unfit patients, preoperative treatment might have no meaningful survival benefit and may even cause harm.…”

“…We assumed that the death event rate would increase in the unfit (control) patient group up to 50%, while the fit group would average 33.5%, a difference of 16.5% based on previous data. 18 We consider this effect size clinically relevant. Assuming 5% (two-sided) significance and 90% power, 150 events are needed to detect this size of difference in a log-rank survival comparison between the two groups.…”

“…Recently, a retrospective pooled analyses from six centres 21 showed that the discriminatory ability of CPET for determining risk of morbidity and mortality after oesophagogastric cancer surgery was poor. Given the early data reporting that preoperative CPET predicts postoperative outcomes, 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 these findings are surprising, however the single-centre nature of these studies, combined with relatively small cohort sizes may contribute. The reasons for the limited predictive utility of CPET and outcomes published recently in oesophagogastric surgery patients in comparison to other surgical settings remains unclear.…”

“…In oesophagogastric surgery, the evidence for CPET is based on relatively small single-centre observational studies ( n =78–273). 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 These studies have yielded inconsistent associations between CPET (VO 2 at peak, 12 AT, 13 , 19 both VO 2 at peak and AT, 15 and V E /VCO 2 14 ) and surgical outcomes. A meta-analysis 20 demonstrated associations between VO 2 at peak, cardiopulmonary complications and 1-yr survival, however the effect size was small and its risk discrimination poor.…”