Cardiopulmonary Exercise Variables Are Associated With Postoperative Morbidity and Mortality After Major Oesophagogastric Cancer Surgery - A Multicentre Observational Study

Study overview and background

We hypothesise that reduced physical fitness (measured objectively using Cardiopulmonary Exercise Testing (CPET)) will result in worse post-operative surgical outcome (reduced overall survival, and increased in-hospital morbidity measured by Clavien-Dindo-Demartines Score). We propose multicentre patient recruitment and analyses of routinely collected clinical data, in an attempt interrogate this hypothesis in patients prior to upper gastrointestinal cancer surgery. Patients undergoing cancer therapies pre-operatively (neoadjuvant chemotherapy or chemoradiotherapy) will be included in the analyses. Patients that become ineligible for an operation, mainly due to metastasis or progression of their cancer on neoadjuvant cancer treatments will also be included but will be analysed separately.

Despite advances in anti-cancer therapies, surgery remains the most important treatment for oesophageal and gastric cancer. Major UGI cancer surgery carries substantial morbidity and mortality, particularly in elderly patients and those with co-morbidities. Recent UK cancer audits show 30-day mortality of up to 3% for elective surgery and a 90-day mortality rate of 5.2%. Outcomes after major cancer surgery depend on modifiable factors such as peri-operative medical care and intra-operative technique and what were previously thought to be unmodifiable components, such as the ability of the patient to tolerate surgical trauma. Centralisation of services and optimisation of perioperative pathways have led to improved outcomes, but substantial gains may yet be achieved with accurate and objective preoperative risk prediction.

Current approaches to risk prediction include a plethora of prediction scores and tests, but none have proven efficacy above experienced clinical acumen. More recently reduced physical fitness (objectively measured using CardioPulmonary Exercise Testing - CPET) has been associated with increased postoperative morbidity in a variety of major surgical cohorts. CPET provides an objective method of evaluating physical fitness under stress, partly mimicking the stress of a major surgical event. Accurate risk prediction methods prior to surgery or indeed other forms of 'trauma' like pre-operative cancer therapies might allow better patient selection, permit modification of the patients preoperative status, as well as improve the optimisation of intra- and postoperative management, and enhances shared decision-making. Furthermore CPET allows interrogation of the causes of exercise intolerance, when exercise capacity is reduced, with the exciting opportunity of intolerance modulation for therapeutic gain (Fit for Surgery).

To date, 37 cohort studies (including over 7,800 patients) have reported the relationship between preoperative CPET-derived variables and postoperative outcome. These data have been brought together in several systematic reviews that, in summary, show a remarkably consistent positive correlation between physical fitness and postoperative outcome. The Southampton based Fit-4-Surgery group have clearly demonstrated this in patients undergoing major colorectal surgery, however the relationship between fitness and post-operative outcomes in UGI cancer surgery is not yet well defined.