Non-Pharmacological Interventions for Return to Work and Multidimensional Health-Related Quality of Life in Adults...

Background: Improving health-related quality of life (HRQoL) and return to work (RTW) among adults with cancer are central to cancer survivorship care, but the effects of different non-pharmacological interventions remain unclear. We evaluated exercise, psychoeducational, vocational, and multidisciplinary interventions across RTW and overall and domain-specific HRQoL. Methods: PubMed/MEDLINE, Embase, and CENTRAL were searched from inception to 3 June 2026 for randomised controlled trials reporting HRQoL or RTW. Random-effects models were used to pool standardised mean differences (SMDs) for HRQoL and odds ratios (ORs) for RTW. Risk of bias and evidence certainty were assessed using RoB 2 and GRADE. The protocol was registered in PROSPERO (CRD420261432617). Results: Eighty-one randomised controlled trials involving 11,257 participants were included; 67 assessed HRQoL, 17 assessed RTW, and 3 included both outcomes. Of the 67 HRQoL trials, 39 (58%) enrolled exclusively female participants. Compared with usual care, overall HRQoL improved with psychoeducational (SMD, 0.40; 95% CI, 0.16-0.65), exercise (SMD, 0.38; 95% CI, 0.26-0.50), and multidisciplinary interventions (SMD, 0.39; 95% CI, 0.23-0.55), whereas vocational interventions showed no clear benefit (SMD, -0.09; 95% CI, -0.43-0.25). Exercise was associated with improvements across all six evaluable HRQoL domains. Psychoeducational interventions improved emotional and physical functioning, while multidisciplinary interventions produced a small improvement in physical functioning. For RTW, psychoeducational interventions were associated with higher odds of returning to work (OR, 1.41; 95% CI, 1.15-1.73), as were multidisciplinary interventions (OR, 2.26; 95% CI, 1.15-4.48), although the latter estimate was based on only three trials. Exercise interventions also showed a favourable estimate, although the confidence interval included the null (OR, 1.95; 95% CI, 0.99-3.87), whereas vocational interventions showed no clear benefit (OR, 1.29; 95% CI, 0.81--2.08). Conclusions: The effects of non-pharmacological rehabilitation differed by intervention type and recovery outcome. Exercise provided the broadest HRQoL benefits, whereas psychoeducational interventions showed the clearest benefits for emotional functioning and RTW. These findings support goal-directed, needs-based rehabilitation and may inform clinical and policy decisions on the delivery of psychological, physical, and workplace support in cancer survivorship care.