Background:
Observational studies report exercise improves cancer outcomes. However, definitive level 1 evidence is required, along with greater understanding of theoretical models to motivate individuals to exercise.
Methods:
International, phase III RCT conducted at 55 centres (25 Australian). Patients with stage III or high-risk stage II colon cancer who had completed adjuvant chemotherapy were assigned 1:1 to 3-year structured exercise program (SEP) or health-education material (HEM). SEP was delivered in 48 exercise sessions: Phase I, 1-6 months; Phase 2, 7-12 months; Phase 3, 19-36 months. Adherence was defined as attendance at 75+% SEP sessions in each Phase. Achieving the physical activity target required increase in exercise by 10 MET hrs/week from baseline to 6 months, then maintenance or further increase to a maximum of 27 MET/hrs/week. Primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS), fitness, and physical functioning.
Results:
From 2009 to 2024, 889 patients were randomised to SEP (n=445) or HEM (n=444). With 7.9 years median follow-up, DFS was significantly longer in SEP than HEM (HR for disease recurrence, new primary cancer, or death, 0.72; 95%CI, 0.55-0.94; P=0.02). 5-year DFS was 80.3% in SEP and 73.9% in HEM (difference, 6.4 percentage points; 95% CI, 0.6-12.2). OS was greater in SEP than HEM (HR for death 0.63; 95%CI, 0.43 to 0.94). The 8-year overall survival was 90.3% in SEP and 83.2% in HEM (difference, 7.1 percentage points; 95%CI, 1.8-12.3). Musculoskeletal adverse events were higher in SEP (18.5% vs. 11.5%).
Rates of adherence to SEP sessions were 77%, 63%, and 53% in each Phase respectively. The proportion increasing physical activity levels by 8+ MET hrs/week were 52% (189/362), 55% (186/336), and 47% (111/236) in each of the 3 Phases. SEP reported significantly more positive beliefs for perceived benefit, enjoyment, support, difficulty, confidence, motivation, planning, and opportunity. All social cognitive variables were significantly associated with moderate-to-vigorous physical activity at all follow-up points (Spearman correlations: 0.30 to 0.45).
Conclusion:
A 3-year SEP in colon cancer survivors after completing adjuvant chemotherapy, resulted in significantly improved DFS, OS, physical functioning, objective physical functioning, and fitness. The SEP intervention successfully targeted social cognitive constructs from the theory of planned behavior. Structured exercise programs should be standard of care for patients with localised colon cancer.