We identified 1505 records from the database search and 387 additional records from other sources (fig 1). After screening, 54 articles met our inclusion criteria and we assessed their methodological quality. Of these, 39 articles from 34 studies had at least one common outcome, and there were sufficient data for inclusion in the meta-analysis. Seven studies (21%) and two articles from another two studies had not been included in previous meta-analyses (table 1).23
Twenty two studies (65%) included only patients with breast cancer, three (9%) included only patients with colorectal cancer, one (3%) included only patients with endometrial cancer, and the eight (27%) remaining included patients with different types of cancer. Three studies had more than one intervention group and thus contributed more than one comparison with their control groups to the meta-analysis. Another two studies published both the full and subgroup analyses. Among 43 intervention-control comparisons, the median number of patients analysed was 93 (range 14-641) with a mean age of 55 (39-74). We used 27 (63%) intervention-control comparisons to assess the effects of an aerobic exercise programme, and six (14%) studies had patients who additionally underwent resistance or strength training. The other comparisons were made for strength or tailored training based on preference of patients. The median duration of the physical activity intervention was 13 weeks (range 3-60). Only 13 studies stated the intensity level of physical activity; 11 were of moderate intensity and two were of vigorous intensity. Most control groups were considered sedentary or were assigned no exercise. We assessed 48 outcomes at least twice in the 43 intervention-control comparisons (tables 2 and 3
Fig 1 Selection process of eligible randomised controlled studies
Table 1 Characteristics of 34 randomised controlled trials included in meta-analysis of effect of physical activity in patients after treatment for cancer
Table 2 Study heterogeneity and sources of heterogeneity by meta-regression analysis* of effect of physical activity in patients after treatment for cancer. Meta-regression performed for all outcomes but source of heterogeneity identified only for leg (more ...)
Table 3 Study heterogeneity and sources of heterogeneity by meta-regression analysis of effect of physical activity in patients after treatment for cancer
Meta-analysis of physiological markers
Physiological markers were assessed only in breast cancer studies. Four physiological markers were included in the meta-analysis: insulin-like growth factor-I, insulin, glucose, and homeostatic model assessment. There was no study heterogeneity in these physiological markers, with I2 being 28% at most, and there was no evidence of publication bias (P≥0.47). In three studies, of which two assessed aerobic exercise and the third assessed weight/strength training, physical activity was associated with significantly reduced insulin-like growth factor-I (−12.0 ng/mL, 95% confidence interval −23.3 to −0.5; P=0.04; fig 2) more than the controls) (table 4). No effect was shown for the other physiological markers. Forest plots for all physiological markers can be found on bmj.com.
Fig 2 Association between physical activity and insulin-like growth factor-I (ng/mL) in patients with breast cancer
Table 4 Pooled effects of physical activity in patients after treatment for cancer
Meta-analysis of body composition
There was no study heterogeneity for any of the six body parameters assessed. Physical activity was associated with slightly reduced body mass index (BMI) (−0.4, −0.6 to −0.2; P<0.01) and body weight (−1.1 kg, −1.6 to −0.6 kg; P<0.001) (fig 3) than the control condition (table 4). Publication bias was evident only for the waist:hip ratio (P=0.06) because of one of the three studies reporting a more substantial reduction than the other two. The effect on waist:hip ratio, however, remained insignificant after we removed this study from the meta-analysis. Forest plots for all markers of body composition can be found on bmj.com.
Fig 3 Association between physical activity and BMI, body weight, and waist:hip ratio in patients with cancer
Meta-analysis of physical functions
Except for bench press and leg press, which were assessed only in patients with breast cancer, all other physical functions were assessed in studies on several types of cancer. Substantial heterogeneity was found for leg press, left handgrip, and right handgrip (table 2). The higher quality study reported a smaller increase in leg press, whereas the studies involving older patients or published in recent years reported larger increases in left handgrip and right handgrip. Otherwise, neither heterogeneity nor publication bias was detected (P≥0.12). Physical activity was associated with significantly increased peak oxygen consumption (2.2 mL/kg/min, 1.0 to 3.4; P<0.01), peak power output (21.0 W, 13.0 to 29.1; P<0.01), the distance walked in six minutes (29 m, 4 to 55; P=0.03; fig 4), bench press weight (6 kg, 4 to 8; P<0.01), leg press weight (19 kg, 9 to 28; P<0.01), and right handgrip strength by 3.5 kg, 0.3 to 6.7; P=0.03) (table 4). Forest plots for all markers of physical function can be found on bmj.com.
Fig 4 Association between physical activity and distance (m) walked in six minutes in patients with cancer
Meta-analysis of psychological outcomes
There was no heterogeneity in any of the psychological outcomes except for fatigue measured by the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire and the two hospital anxiety and depression scales (table 3). Measured by the revised Piper fatigue scale, physical activity was associated with slightly reduced fatigue (−1.0, −1.8 to −0.1; P=0.03; fig 5) in three comparisons from two studies on breast cancer compared with the control (table 5). Measured by the Beck depression inventory, physical activity was associated with reduced depression (−4.1, −6.5 to −1.8; P<0.01) in survivors of mixed types of cancer, which was of near clinical importance. No publication bias was found in any of the psychological outcomes (P≥0.82). Forest plots for all markers of psychological outcome can be found on bmj.com.
Fig 5 Association between physical activity and fatigue and depression in patients with cancer
Table 5 Pooled effects of physical activity in patients after treatment for cancer
Meta-analysis of quality of life outcomes
There were 21 quality of life domains included in the meta-analysis and 10 of them exhibited heterogeneity (table 3). Identified sources of heterogeneity were study quality, sample size, type and duration of physical activity, and age. Study quality was strongly and positively associated with sample size, with smaller studies being associated with larger effects of physical activity on emotional function and total domains of the European Organization for Research and Treatment of Cancer. One study in patients with breast cancer found that aerobic plus resistance training was significantly more effective than aerobic training alone on physical, emotional, and functional wellbeing, breast concerns, breast total, and general total scores on the functional assessment of cancer therapy. In addition, the effect of physical activity on breast concerns was significantly greater in younger patients. The age effect, however, was confounded by the duration of physical activity.
In mixed types of cancer survivors, physical activity improved the SF-36 physical function scores by 3.0 points (0.6 to 5.3; P=0.01), social function by 3.4 points (0.4 to 6.4; P=0.03) and mental health by 2.4 points (0.7 to 4.1; P=0.01) (fig 6) compared with the control group (table 5). No publication bias was found in any of the quality of life domains (P=0.21). Forest plots for all markers of quality of life can be found on bmj.com.
Fig 6 Association between physical activity and markers of quality of life (measured by SF-36) in patients with cancer