Review question/objective

The quantitative objectives are to identify the impact of curative colorectal cancer treatment (surgery or adjuvant therapy) on physical activity, functional status and quality of life within one year of treatment or diagnosis.

Background

Physical activity and quality of life are vital in colorectal cancer (CRC) survivorship.It has been established that adequate physical activity levels prevents cancer recurrence,1 decreases the risk of overall mortality,2 and maintains acceptable functional status and quality of life (QoL).3 In the same way, good QoL of life enhances the chances of survival.4

Most published observational studies report the long-term (usually one year or more since diagnosis or treatment) impact of CRC treatment on physical activity and QoL. Short-term (usually within one year since diagnosis or treatment) outcomes of CRC treatment are equally important because they determine the long-term outcomes;5 however this is poorly understood.6 It is vital to understand the immediate impact of treatment, so interventions, resources or services that can potentially be provided for survivors can be determined as early as possible.7,8

Australia and New Zealand have the highest incidence of colorectal cancer.9 The latest data from the Australian Institute of Health and Welfare and Australian Association of Cancer registries (2012) estimates the incidence to be 72.8 and 51.5 per 100,000 in men and women respectively.10 Colorectal cancer mostly affects individuals aged 45 to 64, and is the most frequently occurring cancer in individuals aged 65 and over.11

Surgical resection of the tumor with tumor free margins is the primary treatment modality, but adjuvant treatment is often administered to "mop up"' potential metastases to enhance the probability of survival.12 Adjuvant treatment modalities are dependent on the site and the stage of cancer. As a "gold" standard, Stage 3 colon cancer requires postoperative chemotherapy, and preoperative radiation and/or pre- or postoperative chemotherapy is necessary for rectal cancer.12,13,14 In some cases of high-risk Stage 2 cancers (with T4 involvement, tumor perforation, bowel obstruction, poorly differentiated tumor or venous involvement), adjuvant chemotherapy is also recommended.15,16,17 The efficacy of adjuvant chemotherapy for CRC using fluorouracil plus leucovorin, for six months is well established.2,16 However, recent advances in chemotherapy treatment have prompted a shift to platinum-based chemotherapeutic agents, such as FOLFOX, CapeOx, and XELOX.17,18 For high-risk Stage 2 and Stage 3 rectal cancer, radiation is added to chemotherapy (chemoradiation) preoperatively to downsize the tumor proximal to the circumferential margin or the sphincter apparatus in order to enhance the sphincter preservation rate with surgery.17

While CRC treatment (surgery and/or adjuvant therapy) is often successful, with 66% achieving a five-year relative survival,19 the treatment may be debilitating, with a negative impact on the QoL, physical activity and ability to self-care (functional status), particularly in the early period (up to six months) after initial treatment.8,20,21,22,23,24,25,26,27 The surgical procedure is associated with significant side effects such as pain, sleep disturbance, fatigue, nausea and vomiting, and inactivity, which can impact on physical functioning.28 Following surgery, hospitalization for 12 days or more is anticipated,29,30 which has the potential to delay functional recovery due to decreased levels of in-hospital mobility and hospital-associated deconditioning.31,32 Moreover, 23% to 50% of patients receive adjuvant treatment.33 Symptoms of anorexia, fatigue, lethargy, nausea, pain and peripheral neuropathy are common after adjuvant treatment.16,34,35,36,37 The most prevalent symptoms are pain38 and fatigue,39 which profoundly influence negative deviations in physical activity,26,40,41,42 functional status,43 and QoL.44

Another important factor to consider is age. The highest incidence of CRC is seen in older adults,10 a cohort considered to possess a predisposition to less favorable treatment outcomes due to existing comorbidities,6,29,45 and diminished physical function.46 Studies quantifying the changes in physical activity, functional status and QoL within six months of CRC treatment are scarce. Nevertheless, evidence from three studies demonstrated significant decreases in most physical activity patterns from the pre-treatment period to during or post-treatment.22,23,26 In comparison to pre-treatment levels, the greatest reductions in total physical activity are experienced during treatment.23 In contrast, Chung and colleagues found that total physical activity levels were unchanged before and during treatment.47 Within six months after treatment, physical activity levels increased, although pre-treatment levels were never regained.22,23 Moreover, other studies quantify the impact of treatment based on the maintenance of the recommended physical activity (at least 30 minutes of moderate intensity physical activity per day). From pre-treatment to post-treatment period, findings from studies indicated that 8.4% to 21% of individuals are unable to maintain their sufficient physical activity.3,26,47

The impact of treatment on functional status is mostly studied in older adults. After CRC treatment older adults experience pronounced decline of their self-care capacity.21 Approximately 70% to 80% of older adults become dependent, imposing demands on formal support services and family members to assist with activities of daily living at home.8,21

Quality of living outcomes significantly vary between studies, which is unsurprising given the subjectivity and multidimensionality of QoL.48 For example, in one study social wellbeing was found to improve after treatment,8 but another study demonstrated significant decline in social wellbeing after treatment.22

Emphasized earlier is the importance of short-term outcomes of treatment: they justify treatment modalities and interventions;7 and they dictate resources, support and services that can be provided to patients.8 Searches of the Cochrane Library, the Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports and multiple other databases, including CINAHL, Medline and EMBASE, revealed no prior systematic reviews evaluating the short-term impact of CRC treatment on physical activity, functional status and QoL. It is anticipated that this review will provide a summarized evidence of the short-term impact of CRC treatment on these outcomes, and guide future support and services provided to individuals who are undergoing or completed treatment.

Inclusion criteria

Types of participants

This review will consider studies that include individuals aged 18 years and over who have been diagnosed with CRC.

Types of intervention(s)/phenomena of interest

This review will consider studies that evaluate the impact of curative CRC treatment: surgery and/or adjuvant therapy

Types of outcomes

This review will consider studies that include the following outcome measures assessed within one year of diagnosis or treatment:

Physical activity - any bodily movement produced by skeletal muscles resulting in energy expenditure.49 Physical activity is not exclusive to exercise; activities can also be walking, housework, occupational or leisure. Physical activity can be measured objectively using pedometers or accelerometers,50 or subjectively using self-reported measures.49

Functional status - measured as the capacity to perform all activities of daily living (ADLs) such as walking, showering, and eating; and instrumental ADLs such as (but not limited to) grocery shopping, housekeeping and laundry.46,51

Quality of life - defined as the individual meaning of mental, physical and psychosocial wellbeing,42 as measured by validated tools such as SF-36,52 EORTC-QLQ-C30,53 or FACT-C.54

Types of studies

This review will consider epidemiological study designs including before and after studies, and prospective and retrospective cohort studies.

Search strategy

The search strategy aims to find both published and unpublished studies. A three-step search strategy will be utilized in this review. An initial limited search of MEDLINE and CINAHL will be undertaken followed by an analysis of the text words contained in the title and abstract, and of the index terms used to describe article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Only studies published in English language will be considered for inclusion in this review due to limited funding support. All studies indexed since the inception of the databases will be considered for inclusion to capture all existing literature.

The databases to be searched include:

CINAHL, EMBASE, and Medline

The search for unpublished studies will include:

ProQuest Dissertations and Thesis, OpenGrey

Initial keywords to be used will be:

Colorectal neoplasms OR colorectal carcinoma OR colorectal cancer

AND

Physical activity OR exercise OR function* OR quality of life OR activities of daily living

Assessment of methodological quality

Prior to retrieval, all studies will be assessed for relevance against the inclusion criteria using the Verification of Study Eligibility form (Appendix I) developed by reviewers based on the recommendations of the Cochrane Collaboration.55

Papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix II). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer.

Data extraction

Data will be extracted from papers included in the review using a customized data extraction tool from JBI-MAStARI (Appendix III). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance to the review question and specific objectives.

Data synthesis

Quantitative data will, where possible, be pooled in statistical meta-analysis using Review Manager 5.3.5 software.56 All results will be subject to double data entry.

We anticipate obtaining dichotomous data for physical activity or function, for example, cut-off scores could be used to determine proportions of the populations who experienced functional decline before and after treatment. In such case, the risk difference will be extracted or calculated for analysis. For continuous data, such as change of mean scores (i.e. changes from baseline or before treatment) overtime, the weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard I2 statistic, where 1% to 25%, 26% to 75%, and 75% and above will be interpreted as low, moderate, and high respectively.heterogeneity.55 Moreover, the chi-squared statistic will also be used to determine heterogeneity, where a p value of less than 0.1 will indicate significant heterogeneity.57

Where statistical pooling is not possible, for example due to variation in measurement scales, the findings will be presented in a narrative form including tables and figures to aid in data presentation where appropriate. Additionally, subgroup analyses based on age of participants, type of treatment, or stage of cancer will be performed where possible.

Conflicts of interest

The authors have no conflicts of interest to declare.

References