Esophageal cancer and its curative treatment, typically consisting of neoadjuvant chemoradiotherapy followed by esophagectomy, place a substantial physiological burden on patients. During treatment, many patients experience a decline in physical fitness and nutritional status, both of which are important determinants of postoperative recovery and long-term outcomes. Prehabilitation, a multimodal intervention aimed at improving physical fitness and nutritional status before surgery, has emerged as a promising strategy to strengthen patients’ resilience and support recovery. However, patients with esophageal cancer vary substantially in their response to treatment, highlighting the need to understand treatment trajectories. This thesis investigated trajectories of physical fitness and nutritional status during curative treatment for esophageal cancer, explored differences between patients in these trajectories, and examined factors associated with treatment outcomes and response to prehabilitation. A review of the existing literature demonstrated that physical fitness declines significantly during neoadjuvant therapy and in the first months after esophagectomy. Current evidence further suggests that exercise-based prehabilitation can reduce postoperative pulmonary complications and may improve postoperative quality of life, although evidence for other clinical outcomes remains limited. The studies in this thesis were conducted within the PRIOR study, a multicenter observational study including 240 patients participating in multimodal prehabilitation integrated into routine care.
The program combined nutritional support with exercise guidance during neoadjuvant therapy, followed by supervised exercise training and continued dietary support in the period before surgery. The findings showed that, on average, physical fitness and nutritional status declined during neoadjuvant therapy, improved during prehabilitation, and declined again after surgery. Yet these average patterns masked substantial individual variation. Fewer than half of the patients followed a trajectory that reflected the overall group average, highlighting the individual nature of treatment-related changes. Notably, patients with higher baseline fitness levels experienced larger postoperative declines, emphasizing that even patients who initially appear physically fit require careful monitoring throughout treatment. Approximately 65% of patients improved their exercise capacity during prehabilitation, while more than one-third did not. Responses varied considerably between individuals. Patients with lower baseline fitness, greater decline during neoadjuvant therapy, and higher levels of fatigue were more likely to demonstrate improvement. Distinct patient subgroups with different exercise intensity profiles and training capacities were identified, underscoring the importance of tailoring prehabilitation to individual characteristics and needs. The studies also showed that lower exercise capacity, poorer upper leg muscle function, higher fatigue levels, and a higher body mass index before surgery were associated with less favorable postoperative outcomes, supporting a multidimensional preoperative assessment. Patients regarded prehabilitation as both feasible and valuable. Understanding the purpose of the program, feeling personally responsible for contributing to recovery, and receiving support from healthcare professionals and family members were important facilitators of participation. In conclusion, this thesis demonstrates that patient trajectories during curative treatment for esophageal cancer are highly heterogeneous. A comprehensive understanding of these trajectories, combined with multidimensional assessment and individualized support, is essential for developing personalized prehabilitation strategies and optimizing recovery after esophageal cancer surgery.
