The effects of neoadjuvant chemoradiotherapy on physical fitness and morbidity in rectal cancer surgery patients.
BACKGROUND
Neoadjuvant chemoradiotherapy (NACRT) followed by surgery for resectable locally advanced rectal cancer improves outcome compared with surgery alone. Our primary hypothesis was that NACRT impairs objectively-measured physical fitness. We also wished to explore the relationship between fitness and postoperative outcome.


METHODS
In an observational study, we prospectively studied 27 consecutive patients, of whom 25 undertook cardiopulmonary exercise testing (CPET) 2 weeks before and 7 weeks after standardized NACRT, then underwent surgery. In-hospital post-operative morbidity and mortality were recorded. Patients were followed up to 1 year for mortality. Data was analysed blind to clinical details. Receiver-operating characteristic (ROC) analysis defined the predictive value of CPET for in-hospital morbidity at day 5.


RESULTS
Oxygen uptake ( [Formula: see text] in ml kg(-1) min(-1)) at estimated lactate threshold (θˆL) and at peak exercise ( [Formula: see text] at peak in ml kg(-1) min(-1)) both significantly decreased post-NACRT: [Formula: see text] at θˆL 12.1 (pre-NACRT) vs. 10.6 (post-NACRT), p < 0.001 (95%CI -1.7, -1.2); [Formula: see text] at peak 18.1 vs. 16.7, p < 0.001 (95%CI -3.1, -1.0). Optimal [Formula: see text] at θˆL and peak pre-NACRT for predicting postoperative morbidity were 12.0 and 18.1 ( [Formula: see text] at θˆL - AUC = 0.71, 77% sensitive and 75% specific; [Formula: see text] at peak - AUC = 0.75, 78% sensitive and 76% specific). Optimal [Formula: see text] at θˆL and peak post-NACRT for predicting postoperative morbidity were 10.7 and 16.7 ( [Formula: see text] at θˆL - AUC = 0.72, 77% sensitive and 83% specific; [Formula: see text] at peak - AUC = 0.80, 85% sensitive and 83% specific).


CONCLUSIONS
NACRT before major rectal cancer surgery significantly decreased physical fitness as assessed by CPET.
NCT01334593.
Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom. Electronic address: mwest@liverpool.ac.uk.
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MA
West
Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address: lisa.loughney@uhs.nhs.uk.
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Loughney
Colorectal Surgery Research Group, Aintree University Hospitals NHS Foundation Trust, Liverpool, United Kingdom. Electronic address: chris.barben@aintree.nhs.uk.
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Barben
Clatterbridge Cancer Centre, Wirral, United Kingdom. Electronic address: rajaram.sripadam@ccotrust.nhs.uk.
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Sripadam
Department of Musculoskeletal Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom. Electronic address: gkemp@liverpool.ac.uk.
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Kemp
Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Integrative Physiology and Critical Illness Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address: mike.grocott@soton.ac.uk.
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Grocott
Critical Care Research Area, Southampton NIHR Respiratory Biomedical Research Unit, Southampton, United Kingdom; Anaesthesia and Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address: s.jack@soton.ac.uk.
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Jack
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000069287:Capecitabine; D059186:Chemoradiotherapy, Adjuvant; D015331:Cohort Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005080:Exercise Test; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010101:Oxygen Consumption; D010809:Physical Fitness; D011183:Postoperative Complications; D011446:Prospective Studies; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000628:therapy*; D012007:Rectum / Q000601:surgery*
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil
Cancer surgery; Cardiopulmonary exercise testing; Morbidity; Neoadjuvant chemoradiotherapy; Physical fitness; Rectal cancer