The role of prehabilitation in improving peri-operative outcomes in elective colorectal and hepatobiliary cancer surgery

Lambert, Joel and Gaffney, Christopher and Subar, Daren and Keegan, Thomas (2025) The role of prehabilitation in improving peri-operative outcomes in elective colorectal and hepatobiliary cancer surgery. PhD thesis, Lancaster University.

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Abstract

Introduction (chapter 1): This thesis constitutes two studies and a systematic review & meta-analysis. All three have involved different methodologies and two out of the three have been designed to investigate the relationship between prehabilitation and clinical outcomes Methods (chapter 2) Data chapter: This retrospective analysis involved interrogation of a prospectively maintained single-site cardiopulmonary exercise testing (CPET) database to determine what CPET and oncological factors were associated with complications and survival. Methods (chapter 3) The SPECS Trial: This was a randomised-controlled trial comparing standard care with prehabilitation in patients undergoing elective major hepatobiliary (HB) and colorectal cancer resections. Patients were randomised 1:1 to either standard care or prehabilitation. Blood biochemistry, circulatory cytokines, CPET, body composition and handgrip strength(HGS) were measured at baseline, preoperatively and postoperatively to determine biological and physiological responses to an exercise-based prehabilitation programme. Results (chapter 1): Prehabilitation led to a statistically significant reduction in length of hospital stay (LoS) by 2 days. There were no difference in complication rates or mortality. Results (chapter 2): In colorectal cancer patients, a R0 resection margin was associated with improved survival (HR: 0.392 CI 0.167 – 0.998 p=0.038) while female sex conferred significantly better survival (HR 0.464 CI 0.215 – 0.930 p=0.038) compared with males. An increasing number of CRI factors was associated with significantly poorer survival (HR 1.746 CI 1.163 – 2.573 p=0.005). A high VE/VCO2 was associated with a trend towards reduced survival (HR:1.870 CI 0.920 – 3.659 p=0.073). In colorectal liver metastases(CRLM), the main determinants of survival were R0 resection margin (HR 0.341 CI 1.153 – 7.144 p=0.019) and total number of metastasectomies (HR 0.639 CI 0.485 – 0.956 p=0.032). Results(chapter 4): Prehabilitation was associated with a potential cardiovascular protective effect evidenced by reduced PAI-1 and leptin levels. There was a statistically significant improvement in anaerobic threshold (AT) noted in the prehabilitation group compared to standard in the postoperative period. Prehabilitation did not demonstrate improvements in LoS, complication rates or mortality. Conclusions: A moderate intensity exercise-based prehabilitation programme can improve cardiovascular fitness by promoting biological and physiological adaptation in the short to medium term.