Outcomes of surgery for oesophageal cancer with focus on fatigue

• Oesophageal cancer is the 6th leading cause of cancer mortality globally. Extensive surgery (oesophagectomy) with neoadjuvant chemo(radio)therapy is the backbone of curative treatment for oesophageal cancer. The thesis aimed to provide better knowledge of survivorship after oesophagectomy, focusing on cancer-related fatigue. Study I was a population-based cohort study with 2576 patients who underwent oesophageal cancer surgery between 1987 and 2015 in Sweden. Modified Poisson regression models were used to estimate risk ratios (RR) with 95% confidence intervals (CI) comparing patients with or without comorbidity for the risk of reoperation or death within 90 days of oesophagectomy, adjusting for confounders. Patients with Charlson Comorbidity Index ≥2 were associated with 78% increased risk of reoperation or death compared with those with Charlson Comorbidity Index 0 (RR 1.78, 95% CI 1.44-2.20). Study II was a nationwide cohort study with 331 patients operated on for oesophageal cancer between 2013 and 2018 in Sweden. Linear mixed-effect models were used to produce adjusted cancer-related fatigue scores and mean score differences (MD) with 95% CIs between patients with and without predefined postoperative complications within 30 days after oesophagectomy. Patients with any postoperative complications had increased cancer-related fatigue scores with clinical relevance (MD 5.8, 95% CI 2.6-9.0) between 1-1.5 years, and remained at the same level until 2 years after the surgery. By stratification, medical and pulmonary complications were associated with increased cancer-related fatigue. Study III was a nationwide cohort study with 356 patients surgically treated for oesophageal cancer between 2013 and 2019 in Sweden. Longitudinal cancer-related fatigue trajectories were identified by growth mixture models. Linear and logistic regression models were fitted and showed that no associations were found between body mass index adjusted weight loss grading system and cancer-related fatigue between 1-3 years after oesophagectomy, with adjustment for confounders. Study IV was a nationwide, longitudinal cohort study including 409 patients who underwent oesophagectomy for oesophageal cancer between 2013 and 2020 in Sweden. Growth mixture models identified 2 distinct overall cancer-related fatigue trajectories between 1-5 years after the surgery. Weighted logistic regression models were fitted to explore factors underlying such trajectories. Comorbidity, pathological tumour stage, postoperative complications, and patient-reported outcomes including anxiety, depression, and pain were associated with high levels of fatigue trajectories. To conclude, preoperative comorbidities were associated with increased risk of reoperation or death after oesophagectomy, and patients after oesophageal cancer surgery might have distinctly different cancer-related fatigue trajectories. More comorbidities, advanced tumour stage, postoperative complications, anxiety, depression, and pain might be associated with the trajectory with higher levels of cancer-related fatigue.

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