Postoperative Exercise Training and Colorectal Cancer Liver Metastasis (mCRC-POET)

Up to 25% of colorectal cancer (CRC) patients are diagnosed with liver metastases, which is the most common site of metastasis, already during the primary tumor diagnosis. Another 30% of the patients will develop liver metastases at a later stage. Even though patient can be treated by surgical resection of the metastatic tumor, 50-75% of the patients experience a relapse in less than two years. Due to the high probability of relapse, mCRC patients undergo multiple rounds of surgery and adjuvant treatment (chemotherapy/radiotherapy) which results in substantial physical de-conditioning. Physical activity has been shown to increase the progression-free survival rates in mCRC patients, when applied post-diagnosis. Increased cardiorespiratory fitness (VO2peak) at the time of diagnosis among CRC individuals has been associated with lower risk of all-cause mortality. Although data on the effect of chronic exercise on VO2peak have emerged, thus far, there is no randomized clinical trial that has investigated the effects of exercise training in mCRC patients early after surgical treatment with curative intent. Therefore, this project aims to address the beneficial effect of structured exercise training primarily on VO2peak and tumor recurrence in mCRC patients immediately after surgical treatment and while they are undergoing adjuvant chemotherapy/radiotherapy. A total of 66 participants will be recruited from the Department of Surgery and Transplantation, Rigshospitalet and randomly allocated to a standard care control group (n=22), standard care plus 150 min/week exercise training (n=22) or standard care plus 300 min/week exercise training (n=22). Participants will undergo exercise training for 6 months, starting immediately after surgery, and they will be followed for additional 6 months. Tumor recurrence will be evaluated up to 3 years after training initiation.

Changes in VO2peak assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer

Changes in ventilatory threshold assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer

Changes in peak power output assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer

Changes in resting leukocyte differential counts (total and per type [eosinophils, basophils, lymphocytes, monocytes, neutrophils])

Patient-reported symptomatic adverse events, assessed using the using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Changes in patient-reported physical well-being assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-28, the higher the score the better quality of life)

Changes in patient-reported social well-being assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-28, the higher the score the better quality of life)

Changes in patient-reported emotional well-being assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-24, the higher the score the better quality of life)

Changes in patient-reported functional well-being assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-28, the higher the score the better quality of life)

Changes in patient-reported general health-related qualify of life assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-108, the higher the score the better quality of life)

Changes in patient-reported colorectal-cancer specific health-related quality of life assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-28, the higher the score the better quality of life)

Changes in patient-reported in health-related quality of life (total score) assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-136, the higher the score the better quality of life)

Changes in patient-reported trial outcome index assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-84, the higher the score the better quality of life)

Changes in patient-reported fatigue assessed using the Functional Assessment of Cancer Therapy - Fatigue scale (FACIT-Fatigue) (scale score: 0-52, the higher the score the less fatigue)

Changes in patient-reported depression, assessed using the Hospital Anxiety and Depression Scale (HADS) (scale scoring: 0-21, the higher the score the worse the condition)

Changes in patient-reported anxiety, assessed using the Hospital Anxiety and Depression Scale (HADS) (scale scoring: 0-21, the higher the score the worse the condition)

Changes in patient-reported weekly duration of walking, assessed using the International Physical Activity Questionnaire (IPAQ)

Changes in patient-reported weekly duration of moderate intensity physical activity, assessed using the International Physical Activity Questionnaire (IPAQ)

Changes in patient-reported weekly duration of vigorous intensity physical activity, assessed using the International Physical Activity Questionnaire (IPAQ)

Changes in patient-reported weekly duration of total intensity physical activity, assessed using the International Physical Activity Questionnaire (IPAQ) (Expressed as metabolic equivalent (MET)-min per week: MET level x minutes of activity x events per week)

Changes in patient-reported weekly sitting time, assessed using the International Physical Activity Questionnaire (IPAQ)

RDI (%) of adjuvant chemotherapy, calculated as the actual dose intensity / standard dose intensity x 100%

Incidence of postoperative hospital re-admissions, defined as any non-scheduled ≥ 24 h hospitalization

Incidence of postoperative complications up to 30 days after surgery (total and by grade and type), assessed using the Clavien-Dindo classification

Inclusion Criteria: Colorectal cancer patients diagnosed with liver metastasis and scheduled for liver metastasis surgical resection Exclusion Criteria: Age <18 Pregnancy Physical or mental disabilities that prohibit execution of test or training procedures Inability to understand the Danish language.