Cancer Survivor (CS), the most widely used definition is: “being a CS, starts on the day of diagnosis and continues until the end of life. Three cancer survivorship phases can be distinguished: “acute survivorship” (i.e., early-stage or time during curative treatment), “permanent survivorship” (i.e., living with cancer or also called the palliative stage), and “extended survivorship” (i.e., cured but not free of suffering). Chronic pain is one of these and occurs in 40% of CSs. Chronic pain is defined by the International Association for the Study of Pain (IASP) as pain that persists or recurs for longer than three month. Unrelieved pain can have considerable adverse consequences on a CSs’ quality of life.
Lifestyle Factor | First Author, Year Published, Study Type | Included Population | Number of Included Studies (n1) and Participants (n2) | Detail of Lifestyle Factor/Intervention Assessed | Main Results in Context of the Specified State-of-the-Art | Level of Evidence [46] |
---|---|---|---|---|---|---|
Alcohol consumption | Leysen et al., 2017, Systematic review with meta-analysis [5] | Breast Cancer Survivors | n1 = 2 (1 CS and 1 C) and n2 = 2519 |
Alcohol use | Alcohol (OR 0.94, 95% CI [0.47, 1.89], p = 0.86, I2 = 67%) was not a predictor for pain, Inconsistent and low evidence |
3b |
Diet | Kim et al., 2018, Systematic review of systematic reviews [47] | Breast Cancer Survivors with AIA | n1 = 3 (systematic review of RCT), and n2_Omega-3 = 817, and n2_VD = 453 | Omega-3 Fatty Acids, and Vitamin D | Significant effects were found for omega-3 fatty acids (MD −2.10, 95% CI [−3.23, −0.97]), and vitamin D (MD 0.63, 95% CI [0.13, 1.13]) on pain, Low evidence |
1a |
Yilmaz et al., 2021, Systematic review [48] | Cancer Survivors | n1 = 2 (uncontrolled clinical trial) and n2 = 77 | Nutritional supplements: vitamin C, chondroitin, and glucosamine | Lack of evidence | 2a | |
Obesity | Leysen et al., 2017, Systematic review with meta-analysis [5] | Breast Cancer Survivors | n1 = 7 (4 CS and 3 C) and n2 = 5573 |
BMI | BMI > 30 (OR 1.34, 95% CI [1.08, 1.67], p = 0.008, I2 = 33%,) was a predictor for pain, Consistent and low evidence |
3b |
Timmins et al., 2021, Systematic review [49] | Cancer Survivors | n1 = 16 (3 CS, 11 C, and 2 retrospective chart review) and n2 = 14,033 | Obesity | According to the SORT: the association between obesity and CIPN was good-to-moderate patient-centred evidence | 3b | |
Physical Activity | Boing et al., 2020, Systematic review with meta-analysis [50] | Breast Cancer Survivors with AIA | n1 = 3 (2 RCT, 1 pilot study), and n2 = 118 | Exercise | Significant effect was found on pain (SMD −0.55, 95 % CI [−1.11, −0.00], p = 0.05 I2 = 80%), Low Evidence |
1b |
Kim et al., 2018, Systematic review of systematic reviews [47] | Breast Cancer Survivors with AIA | n1 = 2 (systematic review of RCT), and n2 = 262 | Aerobic Exercise | No significant effect was found on pain (MD −0.80, 95% CI [−1.33, 0.016]), Low evidence | 1a | |
Lavín-Pérez et al., 2021, Systematic review with meta-analysis [51] | Cancer Survivors | n1 = 7 (RCT), and n2 = 355 | Exercise (HIT) | Significant effect was found on pain (SMD −0.18, 95% CI [−0.34, −0.02], p = 0.02, I2 = 4%), Moderate evidence | 1a | |
Lu et al., 2020, Systematic review with meta-analysis [52] | Breast Cancer Survivors with AIA | n1 = 6 (RCT), and n2 = 416 | Exercise | Significant effect was found on pain (SMD −0.46, 95% CI [−0.79, −0.13], p = 0.006, I2 = 63%), Moderate evidence |
1a | |
Timmins et al., 2021, Systematic review [49] | Cancer Survivors | n1 = 5 (2 C and 3 CS), and n2 = 3950 | Low physical activity | According to the SORT: the association between physical inactivity and CIPN was of moderate evidence | 3b | |
Sleep | Leysen et al., 2019, Systematic review with meta-analysis [53] | Breast Cancer Survivors | n1 = 4 (2 CS and 2 C) and n2 = 1907 | Sleep Disturbances | Pain was a predictor for sleep disturbances (OR 1.68, 95% CI [1.19, 2.37], p = 0.05, I2 = 55%, after subgroup analysis OR 2.31, 95% CI [1.36, 3.92], p = 0.002, I2 = 27%) |
3b |
Smoking | Leysen et al., 2017, Systematic review with meta-analysis [5] | Breast Cancer Survivors | n1 = 2 (1 CS and 1 C) and n2 = 2519 |
Smoking status | Smoking (OR 0.75, 95% CI [0.62, 0.92], p = 0.005, I2 = 0%) was not a predictor for pain, Consistent and low evidence | 3b |
Stress | Syrowatka et al., 2017, Systematic review [37] |
Breast Cancer Survivors | n1 = 12 (6 CS and 6 C) and n2 = 7842 | Distress | Pain was significantly associated with distress: 9/12 studies (75%) | 3b |
Intervention | Chang et al., 2020, Systematic review with meta-analysis [45] | Breast Cancer Survivors | n1 = 5 (RCT) and n2 = 827 |
Mindfulness-Based interventions | No significant effect was found on pain (SMD −0.39, 95% CI, [−0.81, 0.03], p = 0.07, I2 = 85%), Moderate evidence | 1a |
Cillessen et al., 2019, Systematic review with meta-analysis [54] | Cancer Patients and Survivors | n1 = 4 (RCT) and n2 = 587 |
Mindfulness-Based interventions | Significant effect was found on pain (ES 0.2, 95% CI [0.04, 0.36], p = 0.16, I2 = 0%), Moderate evidence | 1a | |
Martinez-Miranda [21] | Breast Cancer Survivors | n1 = 2 (RCT) and n2 = 134 |
Patient Education | No significant effect was found on pain (SMD −0.05, 95% CI [−0.26, 0.17], p = 0.67, I2 = 0%, Low evidence |
1a | |
Silva et al., 2019, Systematic review [55] | Cancer Survivors | n1 = 4 (4 quasi-experimental studies), and n2 = 522 | Promoting healthy behaviour by mHealth apps | Effect found on pain was inconsistent and of low quality of evidence | 2b |
Obesity is a condition characterised by an increase in body fat [83,84][75][76]. At the neurobiological level, obesity is considered to cause pain through various mechanisms, including inflammation and hormone imbalance [85][77]. At the mechanical level, obesity can also cause pain by structural overloading [84[76][78],86], which can lead to altered body posture and joint misuse [87][79]. The latest review in taxane- and platinum-treated CSs demonstrated a good-to-moderate relationship between obesity and higher severity or incidence of chemotherapy-induced peripheral neuropathy (CIPN), with moderate evidence showing diabetes did not increase incidence or severity of CIPN [88][80]. Furthermore, a systematic review with meta-analyses of Leysen et al., (2017) demonstrated that breast CSs with a BMI > 30 have a higher risk (odds ratio = 1.34, 95% CI 1.08–1.67) of developing pain (Table 1, Figure 2) [12]. However, more research is needed to determine the long-term impact of obesity among the expanding population of CSs [89][81]. Studies looking at the link between changes in body mass index, fat mass, inflammatory markers, and chronic pain might help us better comprehend the relationship between these variables in the CS population. Additionally, well-designed, high-quality randomised controlled trials on the effect of combined weight loss/pain therapies are required to inform patients and clinicians on how to personalise the approach to reduce chronic pain prevalence, intensity, or severity in CSs through obesity management (Figure 2).
Pain might be one of the barriers to smoking cessation in CSs [98][82]. An observational study by Aigner et al., (2016) demonstrated that when patients experience higher pain levels, they usually smoke a larger number of cigarettes during these days and initiate fewer attempts to quit smoking [98][82]. This can be explained by the fact that nicotine produces an acute analgesic effect, making it much harder for them to stop due to the rewarding sensation they experience [99][83]. Despite its short-term analgesic effect, tobacco smoking sustains pain in the long-term [93][84]. This underlines the importance of incorporating anti-smoking medications in CSs with pain to avoid relapse during nicotine withdrawal [99][83]. Moreover, pain management should be added to the counselling aspect to enhance the patient’s knowledge, which in turn, might improve their adherence to the whole smoking cessation program [98][82]. Furthermore, the 5As (Ask, Advise, Assess, Assist, Arrange) approach, which assesses the willingness of the patient to quit smoking, is no longer recommended since studies have demonstrated that smokers who did not feel ready to quit smoking at the same rate as those who wanted to [100][85]. The model with the most promising results might be “opt-out”, during which health care providers offer counselling and pharmacotherapy to all smokers, which is more ethical [101][86]. However, research on how to integrate this approach in current cancer care for CSs is needed.
The impact of alcohol use on pain is poorly investigated in CSs, but according to one systematic review of two cohort studies, the risk of developing pain can be reduced by alcohol use (Table 1) [12]. This finding might be misleading due to the fact that alcohol has an acute analgesic effect [111][87]. In non-cancer populations, studies demonstrated that this analgesic effect diminishes over time, and there is an association between chronic pain and alcohol consumption [112][88]. This pain might be evoked by developing alcoholic neuropathy, musculoskeletal disorders, or alcohol withdrawal [112][88]. Conversely, chronic pain increases the risk of alcohol abuse [113][89]. Nevertheless, psychosocial factors are also highly present in patients with alcohol abuse and can be attributed to abnormalities in the reward system of the brain [114][90]. Additionally, a recently published study demonstrated that chronic pain patients with high levels of pain catastrophising are more likely to be heavy drinkers [115][91]. General advice on alcohol consumption after cancer is currently not possible due to the high variability of results in different CSs. Therefore, health care providers should tailor their advice according to cancer types and patients [116][92]. Within that view, an overview of recommendations regarding individualised alcohol consumption for each CS type could support clinicians in doing so, yet such evidence-based recommendations are currently lacking (Figure 2).
First, it is recommended that researchers make a clear distinction between CSs’ phases when initiating and reporting studies in CSs. Currently, the term CS is too globally used, making it difficult to compare or combine results of studies due to their high heterogeneity. An individual in palliative care has different needs than an individual that is cured of cancer; however, both are CSs according to the most widely used definition [4]. A distinction between the different phases has been described by Mullan et al. in 1985 [138]. Unfortunately, these terms are not frequently used in the literature [138] even though a clear distinction between phases could help clinicians to communicate more easily and to provide the appropriate care to patients’ needs according to their phase in the survival of cancer.
Second, most studies were performed on Caucasian breast CSs with high socio-economic status. This population is more likely to have a higher adherence and willingness to change their lifestyle habits [139]. However, to reach a better understanding of barriers for lifestyle changes, research needs to be performed among CS populations with diverse socio-economic backgrounds. This way, oncological care for CSs can be more tailored to patients of different gender, race, and socio-economic capacities.
Third, future studies regarding lifestyle factors in CSs should more thoroughly account for possible confounders. Indeed, research studying a particular lifestyle factor should not only be adjusted for age, gender, education, and so forth, but also for other established lifestyle factors, which might be a considerable confounder. Furthermore, the effects of lifestyle factors in CSs are most often observed over a short period, preventing to draw conclusions regarding long-term impact of lifestyle factors in CSs. More research is warranted to observe the long-term effects of pain management and healthy lifestyle interventions in CSs.
The literature indicates that implementing healthy lifestyle habits in CSs has low compliance rates [140]. A barrier that might cause low adherence to healthy lifestyle behaviours is the burdensome treatment format of most behavioural interventions [73,74]. Therefore, stepped care models might provide clinicians with a possible solution to improve the feasibility and deliver care efficiently [141]. In existing stepped care models, the first step is typically a form of self-management therapy (e.g., recommendations) with the possibility to progress to the highest step of six to eight individual sessions with a specialist, if needed [142,143]. For example, a recent study in CSs demonstrated that more than 50% of CSs with insomnia benefit form a one-hour group-delivered session that empowers CSs by teaching them about sleep health and provides specific information on how to adapt their sleep behaviours [142]. Interestingly, they found that CSs who had experienced sleep problems for a shorter period and perceived less burden from their sleep problems were most likely to benefit from the one-hour program, suggesting that it is crucial to identify CS with sleep problems as soon as possible to enhance the efficacy of low-intensity interventions [142]. However, further research is warranted before implementing stepped care for the other lifestyle factors. In addition, systematic reviews demonstrated promising findings for virtual therapy, suggesting that virtual interventions might be a possible option to enhance access to care, which solves the distance issue [69,137,144].
Furthermore, to reduce the treatment burden, clinicians should perform early screenings and identify negative predictors to improve patients’ self-efficacy to sustain a healthy lifestyle. Developing evidence-based guidelines, including algorithms with practical triage and referral plans to other healthcare professionals, will improve survivorship care. Enhancing the productivity of oncological care by 2025 is of utmost importance because there will be a shortage of oncologists due to the growing cancer population [145]. Besides that, many clinicians have difficulties providing the ideal pain management plan and delivering health promotion guidance due to a lack of knowledge [22]. Supplementary support and educational interventions should be organized for health care providers to enhance their expertise and confidence in this field.
Another recommendation for future clinical practice is considering the use of pain neuroscience education as a way to decrease the threatening nature of pain, catastrophic thinking and fear-avoidance beliefs in CSs [146]. Cancer patients indicate themselves that they have insufficient knowledge regarding pain during or after cancer, what the possibilities of pain relief are and how they can access support when needed [24,25]. When comparing pain knowledge between CSs, healthy controls and caregivers, CSs had the lowest pain knowledge of the three groups [147]. Education about pain is underused in the field of oncology and non-existent in the survivorship phase [148]. Pain neuroscience education can clear the path for more active approaches to pain management, including providing lifestyle interventions. Manuals with guidelines for clinicians on how to explain pain following cancer [146], including accounting for perceived injustice during pain neuroscience education [149], are available to support clinicians in doing so.
Lastly, this state-of-the-art paper underlines once more the complexity of managing chronic pain in CSs. As discussed previously, adopting a healthy lifestyle might have a beneficial influence on the chronic pain of CSs. Unfortunately, there is currently a lack of research about the effectiveness of modifiable lifestyle factors on pain. Moreover, pain in CSs should be targeted on cognitive, behavioural, sensory and emotional levels due to its complexity [18]. Therefore, all pain interventions should be multidisciplinary and personalized for each CS [19].
Emerging evidence shows that CSs find it challenging to receive optimal treatment plans for their burdens, and support or reinforcement to maintain a healthy lifestyle. Therefore, it is crucially important to prepare clinicians well, so they can provide guidance along and after primary treatment. For chronic pain in CSs, it is primordial to identify factors that contribute to the transition of acute to chronic pain in CSs because chronic pain remains underrecognized and mistreated in this population. Furthermore, a proper definition between CSs’ phases should be developed for optimal research and treatment. In the clinical field, new psychosocial factors and modifiable lifestyle factors should be targeted to improve pain relief in CSs.
Modifiable lifestyle factors and their impact on pain have been discussed in depth in this paper and are, for instance, stress, insomnia, diet, obesity, smoking, alcohol consumption and physical activity. First, an inappropriate stress response promotes pain by dysregulating the autonomic, endocrine, and immune response creating a problematic back loop because pain is a manageable risk factor for distress. The stress response can be managed by CBSM, CBT, MBSR and yoga. Second, sleep and pain also form a vicious cycle (sleep problems exacerbate response to nociceptive stimuli and pain can disturb sleep quality) that CBT-I can break. Third, guidelines recommend prudent diets in CSs. However, more research is needed to unravel the role of nutrition and obesity in CSs. Fourth, alcohol consumption and smoking are both negative lifestyle behaviours that impact patients’ general health. Smoking cessation should consist of behaviour therapy and medication. Last, physical activity demonstrates its beneficial impact in several systematic reviews. However, the adherence is low and new treatment strategies such as motivational interviewing or BGA should be investigated in CSs to increase treatment outcomes in the long-term.
In the future, there will be an insufficient number of professionals (oncologists) due to the growing cancer population [150,151]. Therefore, it is a priority that researchers refine current treatment plans and define the benefits of modifiable lifestyle factors and their impact on chronic pain in CSs.