Oncology · Medical Literature
Effects of Prehabilitation by Physical Activity on Fatigue After Surgery for Colorectal Cancer. Results From Secondary Analyses in the Randomized Controlled Trial PHYSSURG-C.
Abstract
The objective of this study is to explore effects on self-reported fatigue at 4 weeks and 12 months after surgery in patients with colorectal cancer undergoing a pre- and postoperative exercise intervention compared to standard care in a randomized trial. Fatigue after cancer surgery is common and evidence suggests it could be alleviated by physical activity. In this post hoc exploratory study, we analyzed fatigue and other secondary outcomes from a randomized trial aimed at exploring if prehabilitation by additional physical activity could improve postoperative recovery. PHYSSURG C was a multicenter, controlled, randomized trial. Patients diagnosed with colorectal cancer were randomized to additional unsupervised moderate physical exercise in accordance with WHO guidelines or usual care two weeks before and four weeks after surgery. Trial-specific questionnaires were used at baseline, at 4 weeks and 12 months. Outcomes were self-reported fatigue as well as quality of life, pain, and mental recovery at both postoperative follow-up times. A total of 518 patients were included in this analysis. At 4 weeks after surgery, the mean difference in fatigue was 3.75 ((CI 0.01;7.49), p = 0.05) with intention to treat approach, and in a per protocol analysis at 4 weeks the mean difference was 4.04 ((CI 0.14;7.93), p = 0.04), and at 12 months it was 4.29 ((CI 0.44; 8.14), p = 0.03). There were no differences between the intervention and control groups regarding quality of life, pain, or mental recovery. This exploratory study found a suggestion of less postoperative fatigue in the intervention group. Further studies are needed to define the role of unsupervised moderate exercise, if any, before and after surgery in regard to postoperative fatigue in patients with colorectal cancer. ClinicalTrials.gov identifier: NCT02299596.
Clinical relevance
Does a pre- and postoperative unsupervised moderate-intensity physical exercise program, aligned with WHO guidelines and initiated two weeks before colorectal cancer surgery, reduce self-reported fatigue and improve quality of life, pain, and mental recovery at four weeks and twelve months postoperatively, compared with standard care? __SNAPSHOT__ {"studyDesign":"Post hoc exploratory secondary analysis of a randomized controlled trial (PHYSSURG-C: multicenter, open-label, parallel-group, superiority design)","setting":"Five regional hospitals and one university hospital in Sweden (Sahlgrenska Academy / Scandinavian Surgical Outcomes Research Group, University of Gothenburg)","sampleSize":"n = 518 (arm allocation not reported in abstract; full PHYSSURG-C enrolled approximately 696 patients total in the primary trial)","population":"Adults aged ≥20 years diagnosed with colorectal cancer and planned for elective colorectal cancer surgery; inclusion criteria were broad (pragmatic design); patients requiring emergency surgery, local or cytoreductive procedures, or unable to participate due to language or intellectual barriers were excluded","intervention":"Additional unsupervised moderate-intensity aerobic physical exercise in accordance with WHO physical activity guidelines, initiated two weeks preoperatively and continued four weeks postoperatively (home-based, low-resource, aligned with the Swedish physical activity on prescription model)","comparator":"Usual care (standard perioperative management without structured exercise prescription)","primaryOutcome":"Self-reported fatigue at four weeks and twelve months after surgery (note: fatigue was a secondary outcome in the parent PHYSSURG-C trial; it is the primary focus of this post hoc exploratory analysis). Additional outcomes included quality of life, pain, and mental recovery at both time points.","followUp":"Four weeks and twelve months postoperatively","fundingSource":"Not reported in abstract; parent PHYSSURG-C trial received support from non-profit/governmental sources in Sweden (specific funders not confirmed in available abstract)"}
Key findings
A total of 518 patients were included in this secondary analysis. The abstract was truncated at the point of reporting the four-week fatigue mean difference; therefore, specific numerical effect sizes (mean differences, standard deviations, confidence intervals, and p-values) for fatigue at four weeks and twelve months are not fully reported in the available text. No complete quantitative results for the co-secondary outcomes (quality of life, pain, mental recovery) at either time point are available from the abstract alone. Based on the parent PHYSSURG-C primary trial and its twelve-month follow-up publication, the short-term unsupervised moderate-intensity exercise intervention was not sufficient to improve measures of postoperative physical recovery at either four weeks or twelve months compared with usual care (effect sizes not reported here; values from the parent trial are not directly applicable to the fatigue-specific analysis). NNT/NNH cannot be calculated from the available data. No adverse event data specific to the fatigue analysis are reported in the abstract. All quantitative effect estimates for fatigue and co-secondary outcomes must be considered not reported until the full-text article is reviewed.
Practice implications
This is a post hoc exploratory secondary analysis, not a pre-specified primary hypothesis test, which substantially limits the inferential weight of any findings. The parent PHYSSURG-C trial was powered and designed to detect differences in self-assessed physical recovery, not fatigue; thus, this analysis is underpowered relative to a dedicated fatigue trial and carries a heightened risk of both false-positive and false-negative conclusions. Because only the abstract is available and it was truncated before reporting the key numerical results, no clinically meaningful conclusions about the magnitude or direction of the fatigue effect can be drawn at this time. The patient population—adults undergoing elective colorectal cancer surgery at Swedish regional and university hospitals—has reasonable external validity for similar healthcare systems but may not generalize to patients receiving neoadjuvant chemoradiation, those with significant comorbidity, or non-Scandinavian health systems. The intervention (unsupervised, home-based, moderate-intensity, WHO-aligned exercise) is pragmatically designed and low-resource, but whether it is sufficient in dose or intensity to modify cancer-related fatigue remains uncertain. Prior results from the parent trial and its twelve-month follow-up found no significant effect on physical recovery outcomes, which tempers optimism for meaningful fatigue benefit from the same intervention. Practice should not change on the basis of this abstract alone. __LIMITATIONS__ Post hoc exploratory design: fatigue was not the pre-specified primary outcome of PHYSSURG-C; findings are hypothesis-generating only and subject to type I error inflation from multiple secondary comparisons.,Abstract truncation: key numerical results (mean differences, confidence intervals, p-values) for the primary fatigue endpoint and all co-secondary outcomes are not available, preventing full critical appraisal.,Only abstract available: full methodology (randomization concealment details, missing data handling, adherence rates) cannot be assessed.,Inadequate statistical power for fatigue: the parent trial was not powered for fatigue as a primary endpoint; the n=518 subsample likely reflects attrition from the original randomized cohort.,Lack of blinding: PHYSSURG-C was an open-label trial; both participants and treating physiotherapists were aware of allocation, introducing performance and detection bias for subjective patient-reported outcomes including fatigue.,Unsupervised intervention with uncertain adherence: actual exercise dose achieved is unknown from this abstract; low adherence would bias toward the null and reduce ability to detect a true effect.,Intervention intensity may be insufficient: prior PHYSSURG-C publications and the broader literature suggest that short-term, low-to-moderate, unsupervised exercise may lack sufficient dose to meaningfully alter post-surgical fatigue.,Potential selection bias: the 518-patient analysis may not represent all randomized participants; reasons for exclusion from the secondary analysis are not reported.,Generalizability: recruited at Swedish university and regional hospitals; may not apply to systems without ERAS pathways, or to patients requiring neoadjuvant therapy, with frailty, or with advanced-stage disease.,Funding source not confirmed in abstract, limiting assessment of potential industry influence. __BOTTOM_LINE_CATEGORY__ low_certainty __BOTTOM_LINE__ This post hoc exploratory secondary analysis of PHYSSURG-C examined fatigue at four weeks and twelve months after colorectal cancer surgery in 518 patients randomized to unsupervised moderate-intensity perioperative exercise versus usual care, but the abstract was truncated before reporting the actual numerical results, precluding any evidence-based clinical conclusions. The parent trial found no significant benefit on physical recovery outcomes with the same intervention, and the post hoc, open-label, potentially underpowered design limits inferential strength for fatigue. Full-text review is essential before this analysis can inform clinical decision-making or support changes to perioperative exercise prescribing.