The role of exercise for pain management in adults living with and beyond cancer: a systematic review and meta-analysis.

Introduction

Pain is a common side effect of cancer or cancer treatment that has significant negative impacts across multiple biopsychosocial domains including reduced quality of life [ 1 , 2 ]. Causes of cancer-related pain (CRP) include the tumor or its metastases inflaming or eroding bone, viscera, or nerves, or pain related to tissue or nerve damage induced by cancer treatments (e.g., surgery, chemotherapy, and radiation) [ 3 ]. Because pain is a subjective experience, the core assessment is self-report. Pain impacts approximately 55% of patients during cancer treatment, 39% after curative treatment, and 66% of people living with advanced, metastatic, or terminal disease [ 4 ]. Overall, moderate to severe pain is estimated to affect 38% of people living with and beyond cancer [ 4 ], yet this symptom is often ineffectively managed [ 5 ]. Analgesic therapy (including opioids and non-opioids) is the mainstay of managing CRP, yet this is only one part of pain management, and an integrated approach can be adopted [ 6 ]. With an increased focus on living well in cancer survivorship, there should be a corresponding shift away from only pharmacological therapy to lessen the risk of opioid use not as prescribed and avoid the adverse effects of medications [ 7 ].

Cancer-related pain management is multimodal, and psychological and behavioral components may be considered as additions to analgesic therapy [ 8 ]. Physical activity is an appealing behavioral intervention because it is associated with multiple health benefits and improved survival [ 9 ], is accessible and low cost, with appropriate screening and tailoring, and is safe for people with cancer [ 10 ]. In 2019, an international multidisciplinary roundtable issued consensus exercise guidelines for people living with and beyond cancer [ 11 ]. For some cancer-related health outcomes (i.e., fatigue, depression, anxiety, and lymphedema), the evidence was considered sufficient to recommend exercise. Exercise for CRP management was not included due to insufficient evidence to date. The role of exercise for CRP is not well understood, which is not surprising, considering that the effect of exercise for chronic pain in general is not definitive. In an overview of Cochrane reviews on chronic pain, favorable results (reduced pain) with exercise were reported; however, benefits were inconsistent across studies, and the overall quality of evidence was low [ 12 ].

Several systematic reviews have focused on exercise for breast CRP. For breast cancer-related shoulder pain, Tatham et al. could make no definitive conclusions about exercise due to limited number and heterogeneity of studies [ 13 ]. For post-mastectomy pain, Kannan et al. found significantly reduced pain severity with exercise versus control, but the effect size was considered clinically insignificant [ 14 ]. After adjuvant breast cancer therapy, Lahart et al. found no significant effect of physical activity on pain [ 15 ]. In contrast, broader meta-analyses have shown modest beneficial effects of exercise on CRP [ 16 ], and exercise has been recognized as beneficial for specific cancer populations. For example, physical activity was added to the 2019 National Comprehensive Cancer Network (NCCN) Guidelines for Survivorship for the management of aromatase inhibitor (AI)-induced arthralgias [ 17 ] based on a recent randomized control trial (RCT) [ 18 ]. Given recent contributions to the literature and the potential for benefit combined with low risks, the role of exercise for CRP across tumor groups warrants further exploration. Therefore, the objective of this review was to determine the role of exercise in pain management in adults living with and beyond cancer.

Methods

The protocol was registered using PROSPERO (CRD42021238005; www.crd.york.ac.uk/prospero ). There was one significant deviation from the registered protocol: we planned to include several study designs, but in the process of full-text screening, we narrowed to only randomized and quasi-randomized control trials because of a higher than anticipated number of trials meeting eligibility criteria. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement was followed for reporting [ 19 ]. All supplementary materials, data, and code are openly available at https://osf.io/as2eh/ .

Eligibility criteria

Inclusion criteria were as follows: (1) participants were aged ≥ 18 years old or described as adults; (2) diagnosed with any type, stage, or treatment status of cancer (i.e., before, during, or any amount of time after cancer treatment); (3) the intervention involved physical activity or exercise of any type, intensity, frequency, or duration, as a major component. Physical activity was defined as any bodily movement produced by skeletal muscles, resulting in energy expenditure above resting levels [ 20 ]. Exercise is a type of physical activity that involves planned, structured, and repetitive bodily movement done to maintain or improve one or more components of health or physical fitness [ 20 ]. Examples include aerobic activities (e.g., walking, running, cycling, climbing stairs, water aerobics, aerobic dance, and hiking), resistance exercise (e.g., free weights, machines with stacked weights, elastic tubing, and resistance bands), and other physical activities that target balance and/or flexibility (e.g., yoga, tai chi, or qigong). (4) The comparator(s) involved usual care, no intervention, or wait list control; physical activity (when studies compared two different types of physical activity such as aerobic vs. resistance exercise); or a non-physical activity, active control such as psychological or pharmacological interventions; or any combination of physical activity and non-physical activity components; (5) pain was a primary or secondary outcome measured using self-report questionnaire; (6) the measurement or assessment of pain included a rating of pain intensity/severity or pain interference, or appraisal of the pain experience; (7) published in English; and (8) randomized or quasi-randomized controlled trials.

Exclusion criteria were as follows: (1) psychological interventions such as cognitive behavioral therapy unless physical activity was a major component; (2) physiotherapy or rehabilitation interventions that only involve a single-joint or single-muscle group due to dysfunction in one anatomical region; (3) self-management interventions that included physical activity/exercise education (e.g., a handout of physical activity guidelines) as one of multiple-intervention components; (4) outcomes labeled as “pain” not measured via self-report by the patient (e.g., pain judgments by healthcare providers or observed behavior by researchers); and (5) study protocols, abstracts, or theses.

Information sources

Ovid MEDLINE®, Embase, APA PsycInfo, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched via the Ovid research platform. CINAHL and SPORTDiscus were searched via the EBSCOhost research platform. All databases were searched from inception until August 30, 2021.

Search strategy

The search strategy was developed in collaboration with an academic librarian. The full strategy is available at https://osf.io/as2eh/ .

Selection process

The search results were deduplicated in Zotero using the IEBH Systematic Review Accelerator [ 21 ] and imported into a systematic review software (Rayaan [ 22 ]) for title and abstract screening. The titles and abstracts were independently screened for potential eligibility by two researchers (V. L., M. B.), who were blinded to the other’s decisions. The full text of any record considered potentially eligible by either researcher was retrieved and assessed for eligibility. To determine eligibility for inclusion in the review, full-text screening was completed by one of two researchers (M. B. or B. R.) and approved by a second researcher (R. T.). Discrepancies were resolved by discussion and team consensus. Where multiple records reported findings from the same trial, only one record was included (that which reported pain as an outcome).

Data collection process

Following standardized training, data were extracted into a spreadsheet by a researcher working independently (V. L., M. B., T. D., J. T. D.) and checked by a second researcher within this team. If data for studies included in a meta-analysis could not be extracted from the article, authors were emailed twice with a data request.

Data items

The outcome for which data was sought for meta-analysis was pain (post-intervention and change scores). For all studies, pain related outcomes included the pain scale or sub-scale, the minimal clinically important difference (MCID), the conceptualization of the pain (e.g., severity of interference), and whether pain was an inclusion criterion (and how this was measured/defined). Study-level variables included year of publication, participant enrollment, whether the trial was pre-registered, sample size, study design, aims/hypothesis, trial primary outcome, sample size justification, and loss to attrition. Participant characteristics included age, cancer and cancer treatment type, and other participant eligibility criteria. Intervention characteristics included intervention type, length, physical activity frequency, intensity, duration, and progression of the exercise prescription.

Risk of bias

For studies included in the meta-analysis, risk of bias (ROB) was assessed according to the Cochrane Handbook for Systematic Reviews [ 23 ] using Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB2). Following standardized training, ROB decisions were made by a researcher working independently (B. R.) and checked by a second researcher (R. T. or J. D.).

Synthesis methods

Our primary pre-registered synthesis was a narrative synthesis of studies investigating exercise for CRP. A meta-analysis of the effect of exercise vs. control on post-intervention pain was also performed. Pilot and feasibility trials and trials not powered to detect an effect on pain as a primary outcome were excluded from the meta-analysis. The estimated effect from efficacy trials focused on pain was considered more likely to provide a better estimate of the true effect and less likely to result in an inflated summary effect size. The meta-analysis was performed using an open-source add-on for meta-analysis (the metafor package [ 24 ]) using R [ 25 ] and carried out using the standardized mean difference (SMD) as an effect measure, i.e., Hedges’ g . A random-effect model was fitted to the data. The amount of heterogeneity (tau 2 ) was estimated using a restricted maximum-likelihood estimator [ 25 ], and Cochran’s Q and the I 2 statistic were used (the latter using Cochrane’s rough guide to interpretation [ 26 ]). For trials that contained three arms (two eligible physical activity groups versus a control group), a single pairwise comparison was created by combining data from both groups using methods recommended in the Cochrane Handbook for Systematic Reviews of Interventions [ 27 ]. The 95% prediction interval was calculated because it estimates where the true effects are to be expected for 95% of future similar studies [ 16 ], and points to the clinical implications of the observed heterogeneity [ 28 ]. Begg’s rank test [ 29 ] and Egger’s test [ 30 ] were used to assess funnel plot asymmetry (as a marker of potential publication bias).

Certainty assessment

The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system was used, which classifies the certainty for a body of evidence for a given outcome as one of four levels: high, moderate, low, and very low [ 31 ]. Further guidance was obtained from the GRADE handbook [ 32 ].

Results

The flow diagram of study identification and selection is presented in Fig. 1 . The database search identified 8392 citations, of which 2501 were removed as duplicates. Of the 5891 records screened, 76 studies met the eligibility criteria and were included in this systematic review. Fig. 1 Identification of studies via databases

Narrative synthesis

A total of 76 studies were included [ 18 , 33 – 107 ], with 20 studies reported as pilot studies primarily examining feasibility and preliminary efficacy [ 33 , 39 , 49 , 55 , 59 , 65 , 66 , 68 , 73 , 74 , 78 , 80 – 82 , 84 , 86 , 92 , 95 , 96 , 99 ] and 56 studies examining efficacy (Table 1 ). Studies were largely conducted in the USA ( n = 13) [ 18 , 33 , 47 , 56 , 64 – 66 , 71 , 83 , 89 , 94 , 95 , 107 ] and Canada ( n = 8) [ 34 , 48 , 49 , 73 , 77 , 82 , 85 , 86 ]. Out of the 76 studies included, 57 looked at a single cancer type (e.g., breast only), and 19 pertained to multiple cancer types. Some of the cancer types included breast, lung, prostate, head and neck, testicular, colorectal, or cervical cancer. Among the studies, 39 included participants being on treatment (e.g., chemotherapy, surgery, hormone therapy, or radiotherapy). The data included 15 studies that reported pain as a primary outcome [ 18 , 41 , 45 , 51 , 57 – 59 , 69 , 72 , 78 , 85 , 89 , 90 , 96 , 99 ], with 62 studies reporting pain as a secondary outcome. For studies reporting pain as a primary outcome, breast cancer was the predominant tumor type. For the studies reporting pain as a secondary outcome, individuals with persistent pain or moderate-severe pain were not actively targeted (i.e., level of pain was not an eligibility criteria). The studies included various validated self-report measurements of pain (Table 1 ) with the Visual Analog Scale being used most often. The MICD, or a meaningful change in the pain score considered clinically relevant, was only reported in 10 studies. Table 1 Characteristics of studies that examined the effects of exercise on pain for individuals living with and beyond cancer Author, year, country Average age Cancer type Treatment status Design + sample size Primary outcome Pain measures ACSM intervention Duration of intervention frequency, duration of exercise Intervention effects on pain Adair 2018; USA Intervention: 65.0 ± 7.4 Control: 61.8 ± 9.2 Head and neck Three months post-treatment Feasibility randomized wait controlled trial. Wait list control ( n = 40) Feasibility and preliminary efficacy outcomes Brief Pain Inventory–Short Form (BPI-SF) Resistance, flexibility 8 weeks Pain improved (decreased) in the intervention group and increased in the control group Adams 2018; Canada Intervention: 43.7 ± 10.8 Control: 43.3 ± 9.9 Testicular Off treatment Prospective, two-armed, phase II, randomized controlled trial. Usual care control ( n = 63) Peak aerobic capacity (relative VO2peak) Short Form-36 (SF-36) High-Intensity Interval Training (HIIT): aerobic 12 weeks No significant effects were noted for bodily pain Ali 2021; Egypt Intervention: 51.4 ± 9.2 Control: 49.8 ± 8.6 Breast Post-mastectomy Prospective, single-blinded, parallel-group randomized controlled trial. Active control (land-based exercise) ( n = 50) Limb volume Visual Analog Scale (VAS) Aqua therapy: resistance and aerobic program 8 weeks Significant improvements in pain scores were demonstrated in intervention versus control group Alpozgen 2017; Turkey Pilates: 46.2 ± 11.2 Combined exercise: 51.9 ± 8.2 Home exercise: 51.5 ± 13.8 Breast Post-treatment Randomized controlled trial. Pilates exercise versus home exercise versus combined exercise ( n = 55) NR VAS Pilates: aerobic, resistance, flexibility 8 weeks; 3/week; 35 min Pain levels improved on motion and at rest for all groups. No significant differences between groups Ammitzball 2020; Denmark Intervention: 52 ± 10 Control: 53 ± 10 Breast On treatment Randomized controlled trial. Usual care control ( n = 158) Lymphedema incidence Pain questionnaire comprising multiple pain outcomes, numerical rating scale (NRS) Resistance 50 weeks; 3/week; 60 min No effect of progressive resistance training on post-operative pain Aydin 2021; Turkey 45.0 ± 2.2 Breast Off treatment Randomized controlled trial. Control group was encouraged to maintain exercise levels ( n = 48) Quality of life (QOL), depression levels European Organization for Research and Treatment of Quality of Life–Core Assessment 30 (EORTC QLQ-C30) Aerobic, resistance 12 weeks; 3 days/week; 40–45 min Both groups had significant improvements to pain levels pre- and post-intervention; however, there were no significant differences between the groups post-intervention Backman 2014; Sweden 54 Breast, colorectal On treatment Pilot, randomized controlled trial. Control group given education about exercise ( n = 77) Feasibility and adherence EORTC QLQ-C30 Walking: aerobic 10 weeks Significant differences were found for pain and pain around the operated breast while the control group results were unchanged Bashar 2020; Turkey Intervention: 52 ± 9.9 Control: 53.58 ± 1.92 NR On treatment Single-blind, controlled, prospective clinical study. Usual care control ( n = 70) Balance painDETECT questionnaire Resistance, balance 10 weeks; 5 times/week; 20 min painDETECT questionnaire scores were significantly lower in the exercise group Barbosa 2021; Brazil Pilates: 52.0 Circuit: 54.0 Control: 59.8 Breast On treatment Single-blind randomized controlled trial. Pilates versus circuit exercise versus usual care control group ( n = 60) Pain NRS, Brief Pain Inventory (BPI) Pilates: aerobic, flexibility, resistance 8 weeks; 2 times/week; 75 min The Pilates group demonstrated a significant difference in pain reduction compared to the circuit group Bloomquist 2018; Denmark 45.3 ± 9.2 Breast On treatment Randomized, crossover, equivalence trial. Low load resistance followed by high load resistance ( n = 21) Extracellular fluid NRS Aerobic, resistance 12 weeks; 30 min Equivalence between all breast cancer symptoms including pain was found between low and high load intensities at all time points Bloomquist 2019; Denmark NR Breast On treatment Parallel group, randomized design. High load resistance versus low load resistance ( n = 153) Breast cancer-related arm lymphedema NRS Aerobic, resistance 12 weeks Non-equivalence was found for pain at 39 weeks and tightness at both 12 and 39 weeks favoring those in the high load resistance group Brocki 2014; Denmark Intervention: 64 ± 10 Control: 65 ± 9 Lung On treatment Assessor-blinded, 1:1 parallel-group, randomized controlled trial. Control group given education about exercise ( n = 78) Health-related QoL SF-36 Aerobic, resistance 10 weeks; once/week; 1 h Statistically significant effect of exercise on pain improvement after 4 months Cantarero-Vilanueva 2012; Spain Intervention: 48 ± 8 Control: 47 ± 9 Breast Off treatment Randomized, controlled clinical trial. Usual care control group ( n = 66) Neck and shoulder/axillary pain intensities VAS and pressure pain sensitivity Water physical therapy: aerobic, endurance, core stability 8 weeks; 3 times/week; 1 h The water group experienced a greater decrease in neck and shoulder/axillary pain than the control group. However, no significant changes in widespread pressure pain hyperalgesia were found Cantarero-Vilanueva 2017; Spain Intervention: 57.52 ± 8.05 Control: 62.31 ± 7.93 Colorectal Off treatment A secondary analysis of a randomized controlled clinical trial. Usual care control group ( n = 46) Abdominal isometric endurance Pressure pain threshold and BPI Aerobic, flexibility, resistance (lumbo-pelvic strength) 8 weeks; 3 times/week This physical exercise program was effective for decreasing lumbar and infraumbilical pain Cheville 2013; USA Intervention: 63.8 ± 12.5 Control: 65.5 ± 8.9 Lung or colorectal NR Randomized controlled trial. Usual care control group ( n = 66) Mobility assessed with the Ambulatory Post-Acute Care Basic Mobility Short Form Functional Assessment of Cancer Therapy (FACT)–General Resistance, aerobic 8 weeks; 2 times/week for resistance program and 4 times/week for walking A greater mean difference in pain was found for the intervention group compared with the control group Courneya 2013; Canada Standard exercise: 49.2 ± 8.4 High dose: 50.1 ± 8.8 Combined: 50.5 ± 9.4 Breast On treatment Randomized controlled trial. Standard dose of aerobic exercise versus high dose of aerobic exercise versus combination ( n = 301) Patient-reported physical functioning assessed by SF-36 SF-36 physical functioning subscale Aerobic Started within 1–2 weeks of start of chemotherapy and ended 3–4 weeks post-chemotherapy; 3 times/week; duration based on treatment group (75 min or 150 min) Higher dose of 50 to 60 min of aerobic exercise was superior to both a standard dose of 25 to 30 min of aerobic exercise and a combined dose of 50 to 60 min of aerobic and resistance exercise for pain reduction Crawford 2016; Canada NR Cervical, endometrial, or ovarian cancer NR Pilot randomized controlled trial. Usual care control group ( n = 35) Post-traumatic growth SF-36 Resistance 8 weeks; 2 times/week; 120 min A statistical trend and clinically meaningful group difference in favor of the usual care group for bodily pain was found de Oliveria 2020; Brazil Intervention: 61.5 ± 8.8 Control: 57.6 ± 7.8 Any type of cancer in stage 0 to III Off treatment Controlled, quasi-experimental study. Cancer group compared to non-cancer control group ( n = 38) Strength of middle deltoid muscle and shoulder pain and disability Shoulder Pain and Disability Index (SPADI) Exergaming: aerobic 20 total sessions; 2–3 times/week Exergaming did not reduce the level of pain in the cancer group, whereas there was a significant reduction in the level of pain in the control group Dhawan 2020; India Intervention: 50.5 ± 7.9 Control: 52.5 ± 6.6 NR On treatment Randomized controlled trial. Usual care control group (n = 45) Chemotherapy-induced peripheral neuropathic pain and QoL Leeds Assessment of Neuropathic Symptoms and Signs pain scale Resistance 10 weeks; daily; 30 min There was a statistically significant reduction in mean neuropathic pain in the intervention group as compared with the control group Dimeo 1997; Germany Intervention: 39 ± 10 Control: 40 ± 11 NR On treatment Randomized controlled trial. Usual care control group who did not exercise ( n = 80) Maximal physical performance WHO scale Biking: aerobic Length of hospital stay; daily; 30 min Severity of pain was lower for patients in the intervention group than for control patients Ding 2020; China Intervention: 53.2 ± 6.8 Control: 50.8 ± 7.6 NR On treatment Open parallel randomized controlled trial. Control group performed traditional hand-grip exercises ( n = 98) Peripherally inserted central catheter self-management ability and QoL SF-36 Tai chi: flexibility, resistance 3 months; 5 times/week; 60 min There was no statistical difference between the bodily pain scores of the observation group and the control group Do 2015; South Korea Intervention: 47.1 ± 8.5 Control: 48.3 ± 8.2 Breast NR Prospective randomized controlled trial. Wait list control group ( n = 212) NR Subscale of EORTC-QLQ30 Aerobic, resistance, flexibility 8 weeks; 5 times/week; 10-min warm up, 8–12-repetition strength, and 40 min of aerobic Statistically significant differences in pain were found between the two groups post-treatment Do 2017; South Korea Intervention: 57.5 ± 7.7 Control: 55.9 ± 12.7 Cervical, endometrial, or ovarian cancer Off treatment Pilot, randomized study. Control group received lymphedema treatment from physio-therapist ( n = 44) NR EORTC-QLQ30 Flexibility, resistance, aerobic 4 weeks; 5 times/week; 40 min Improvement after treatment was significant in both groups for pain Dodd 2010; USA Exercise during chemotherapy: 49.4 ± 8.2 Exercise after chemotherapy: 50.5 ± 9.4 Usual care: 52.0 ± 10.8 Breast, colorectal, or ovarian cancer Beginning their first chemotherapy treatment Randomized, single-blind, 3-arm, controlled trial. Exercise during chemotherapy versus exercise post-chemotherapy versus usual care ( n = 119) Cancer-related fatigue The Worst Pain Intensity Scale Aerobic 52 weeks; 3–5 days/week; 20–30 min No significant effects of the exercise program were found between groups or over time Eyigor 2018; Turkey Intervention: 51.5 ± 7.3 Control: 52.3 ± 9.5 Breast Post-treatment Randomized controlled trial. Wait list control group ( n = 42) Arm and shoulder pain intensity VAS Yoga: resistance, flexibility 10 weeks; 2 times/week; 60 min The yoga intervention group showed significant improvement in pain post-intervention Fernandez-Lao 2012; Spain Intervention: 49 ± 8 Control: 47 ± 8 Breast Finished adjuvant treatment except hormone therapy Randomized controlled trial. Usual care control group ( n = 44) Neck and shoulder pain and pressure pain thresholds VAS Aerobic, resistance, and flexibility 8 weeks; 3 times/week; 90 min The intervention was effective in improving neck and shoulder pain, and reducing widespread pressure pain hyperalgesia Fields 2016; Wales, UK Intervention: 60 ± 8 Control: 66 ± 7 Breast On treatment Feasibility randomized controlled trial. Control group received 2 weekly symptom checks and post-treatment exercise educational pamphlet ( n = 40) Aromatase inhibitor (AI)-associated arthralgia BPI-SF Nordic walking: aerobic 12 weeks; 1 time/week for weeks 1 and 2, adding a second 30-min session in weeks 3 and 4, and a third in weeks 5 and 6. In weeks 7–12, participants were asked to complete four From baseline to study end point, pain reduced in both the intervention and control groups Frensham 2018; Australia Intervention: 65.2 ± 9.3 Control: 66.1 ± 9.4 All Off treatment Quasi-randomized controlled intervention trial. Wait list control group ( n = 102) Increased physical activity levels (increased number of steps per day) SF-36 Walking: aerobic 12 weeks Bodily pain increased from baseline to the end of the intervention and follow-up in both groups Galiano-Castillo 2016; Spain Intervention: 47.4 ± 9.6 Control: 49.2 ± 7.9 Breast Post-treatment Randomized controlled trial. Control group received education about exercise ( n = 81) BPI, validated for Brazilian Portuguese Resistance and aerobic 8 weeks; 3 times/week; 90 min The intervention significantly improved pain compared to usual care Galvao 2018; Australia Intervention: 69.7 ± 7.6 Control: 70.0 ± 8.4 Prostate NR Two-armed prospective randomized controlled trial. Usual care control group ( n = 57) Physical function subscale from the SF-36 FACT–Bone Pain Resistance, aerobic, and flexibility 12 weeks; 3 times/week; 60 min There were no changes in bone pain assessed by the FACT–Bone Pain in those who exercised. No reporting of differences between groups Garcia-Soidan 2020; Spain Strength: 63 ± 7 Aqua fitness: 62 ± 6 Aerobic: 64 ± 7 Breast Off treatment A randomized, controlled, experimental trial with 3 × 3 design. Strength training versus aqua fitness versus aerobic ( n = 316) NR Short Form 12 Health Survey (SF-12) Aerobic, resistance 45 weeks of training; 2 times/week; strength: 55–60 min, aqua: 55 min, aerobic: 55 min Significant improvement in pain was found in the strength and aqua fitness groups but not the aerobic group Griffith 2009; USA Intervention: 59.8 ± 10.8 Control: 60.6 ± 10.8 All On treatment Randomized controlled trial. Usual care control ( n = 126) NR 2-item subscale Medical Outcomes Study–Pain Walking: aerobic Duration of cancer treatment; 5 times/week; 20–30 min No significant difference between the exercise and usual care groups on pain scores Hacker 2021; USA Intervention: 62.2 ± 8.5 Control: 63.4 ± 6.3 Multiple myeloma On treatment Pilot randomized controlled trial. Usual care control ( n = 34) NR EORTC QLQ-C30 Aerobic, resistance 6 weeks Both groups showed improvement in pain scores over time Hammer 2021; USA Intervention: 50.2 ± 14.8 Control: 47.2 ± 11.5 Breast, lung, gastro-intestinal, or gynecological cancer Scheduled to start a new cycle of chemotherapy within 2 weeks Pilot, randomized intervention study. Usual care control ( n = 33) Feasibility of participating in the program 11-point NRS Walking: aerobic 6 months; 3 times/week; 30 min The intervention group reported lower symptom scores compared to the control group at 6 months; however, differences were not significant Hayes 2012; Australia Face to face: 51.2 ± 8.8 Telephone: 52.2 ± 8.6 Control: 53.9 ± 7.7 Breast On treatment Randomized controlled trial. Face-to-face versus telephone versus usual care control ( n = 194) QoL Neuropathic Pain Scale Aerobic, resistance 34 weeks; 4 times/week; 180 + min/week Pain improved over time for all groups Henke 2014; Germany NR Non-small-cell lung cancer or small-cell lung cancer in stage IIIA/IIIB IV On treatment Randomized controlled trial feasibility. Enhanced aerobic endurance and strength program versus conventional physiotherapy ( n = 46) QoL and independence German version of EORTC QLQ-C30 Resistance, aerobic, flexibility Start of chemotherapy to third cycle of chemotherapy Significant differences for pain in arms or shoulder were found between groups favoring enhanced aerobic and endurance intervention Ho 2015; China Intervention: 48.6 ± 7.7 Control: 49.1 ± 8.7 Breast Awaiting treatment Randomized controlled trial. Wait list control group ( n = 139) Treatment-related symptoms BPI Dance movement therapy: aerobic, flexibility 3 weeks; 2 times/week; 90 min Dance movement therapy had significant effects on reducing pain severity and pain interference compared to control Hong 2020; China Intervention: 55.4 ± 11.6 Control: 52.3 ± 12.4 Gastro-intestinal On treatment Randomized controlled trial. Relaxation control group ( n = 204) Physical functions (1RP max leg press, seated row, leg extension, and chest press) NR Resistance 12 weeks; 2 times/week; 60 min The incidences of back pain were significantly lower in the treatment versus in the relaxation control group Huberty 2019; USA Intervention: 56.9 ± 10.3 Control: 55.0 ± 10.3 Myeloproliferative neoplasm (MPN) NR Pilot, randomized controlled trial. Wait list control ( n = 62) Symptom burden and QoL PROMIS Pain Intensity Short Form 3a Yoga: flexibility 12 weeks; once weekly; 60 min Online yoga demonstrated small effect on pain versus control group Hwang 2008; South Korea Intervention: 46.3 ± 7.5 Control: 46.3 ± 9.5 Breast On treatment; waitlisted for radiotherapy Randomized controlled trial. Control group NR ( n = 40) QOL, fatigue, range of motion (ROM) of shoulder, and pain VAS Aerobic, resistance, and flexibility 5 weeks; 3 times/week; 50 min There was a significant difference in the change in mean VAS score between groups favoring exercise Ibrahim 2018; Canada 39.2 ± 5 Breast Off treatment; Intervention starts 3–4 weeks after cessation of radiation therapy Pilot randomized controlled trial. Standard care control group ( n = 59) Unclear; maybe pain BPI-SF Resistance, endurance, and flexibility 12 weeks; 2–3 times/week; duration NR There were improvements to pain during shoulder movements at 3 + 6 months post-intervention but not sustained over time into 18 months post-intervention Irwin 2015; USA Intervention: 62 ± 7.0 Control: 60.5 ± 7.0 Breast On treatment; receiving AI for at least 6 months Randomized controlled trial. Usual care control group ( n = 121) Arthralgia Modified BPI Aerobic and resistance 52 weeks; 2 strength sessions; 150 min Statistically significant differences in pain severity and pain interference were observed between exercise vs. control group Jensen 2014; Germany Resistance: 58.7 ± 12 Aerobic: 51.6 ± 13.6 Advanced gastro-intestinal cancer On treatment; undergoing palliative chemotherapy Pilot study. Resistance exercise group versus aerobic exercise group ( n = 26) QOL/feasibility EORTC-QLQ-C30 2 groups; 1 aerobic, 1 resistance 12 weeks; 2 times/week; 45 min In aerobic group greater number of walking steps was associated with lower scores for pain Jiang 2020; China Intervention: 59.3 ± 7.40 Control: 57.5 ± 11.2 Lung Off treatment; after receiving surgery Single-blind randomized controlled trial. Usual care control group ( n = 100) Effect of tai chi on blood oxygen, anti-inflammatory, and anti-oxidant activity VAS for Pain and Prince Henry Score method Tai chi: resistance, flexibility, and balance 13 weeks; daily; 60 min No significant difference in pain scores between the two groups after 1-month surgery. After 2 and 3 months, pain scores in the tai chi group were lower than those in the control group Kim 2019; South Korea Conventional self-exercise: 48.9 ± 7.2 Therapeutic inflatable ball self-exercise: 47.7 ± 8.9 Breast Off treatment; after completing chemotherapy Pragmatic, quasi-experimental design. Conventional self-exercise versus inflatable ball self-exercise ( n = 72) Shoulder ROM and QoL Total Shoulder Pain and Disability Index (SPADI) score Flexibility (ROM) 12 weeks/3 times/week; at least 15 min No significant difference between groups in SPADI pain, disability, or total scores Kirkham 2018; Canada Intervention: 51 ± 9 Control: 50 ± 10 Breast On treatment; doxorubicin treatment Randomized controlled trial. Usual care control group ( n = 27) Global longitudinal strain Prevalence of low back pain Aerobic 24 h before each treatment; 45 min There was significantly reduced low back pain and sore muscles after the last treatment in the intervention compared to the usual care group Klein 2021; Israel Intervention: 53.3 ± 12.7 Control: 51.2 ± 13.1 Breast On treatment Pilot, prospective, randomized clinical trial. Usual care control group ( n = 157) Shoulder pain NRS Resistance and flexibility 1 week and a month; 3 times/week; 5 repetitions of each exercise Intervention significantly reduced pain at 1 and 6 months post-op compared to usual care control Landry 2018; France Intervention: 51 ± 2 Control: 53 ± 4 Breast Unclear; must have had mastectomy Randomized clinical trial. No treatment control group ( n = 23) Self-esteem and QOL (not explicitly stated) EORTC-QLQ-C30 Resistance, flexibility 12 weeks; 1 session/week; 60 min Pain tended to decrease for the exercise group (non-significant) compared to the control group Larsen 2019; Denmark Intervention: 69 ± 9.7 Control: 67 ± 15.3 Multiple myeloma On treatment; high-dose chemotherapy with stem cell support, active anti-myeloma treatment Feasibility, randomized clinical trial. Two-center study, with blinded outcome assessors. Usual care control group ( n = 30) Change in isometric knee extension strength BPI-SF Aerobic, resistance 10 weeks; 3 times/week; 75 min Only feasibility data reported Lee 2010; South Korea Scapula-oriented exercise: 47.5 ± 5.1 General exercise: 45.6 ± 7.0 Control: 47.6 ± 9.2 Breast Off treatment; unilateral breast cancer surgery followed by adjuvant chemotherapy or radiation therapy Pilot, randomized controlled trial. Scapula exercise group versus general exercise group versus historical control ( n = 50) Outcomes include upper extremity disability and QoL, shoulder ROM, and shoulder strength VAS and BPI Resistance, flexibility 8 weeks; once/week; 50 min Pain significantly improved. Scapula-oriented group showed decreased VAS scores. Brief Pain Inventory scores declined significantly only in the scapula-oriented exercise group Letellier 2014; Canada Intervention: 56.4 ± 9.76 Control: 53.4 ± 9.35 Breast Off treatment; after any radiation or chemotherapy; surgery Randomized controlled pilot and feasibility study. Aquatic lymphatic therapy plus home-based exercise (intervention) versus home-based exercise ( n = 25) Pilot/feasibility Short-Form McGill Pain Questionnaire (MPQ) Aerobic 12 weeks; once/week; 60 min Statistically significant decrease in pain intensity for intervention versus control group Litterini 2013; USA Resistance: 62.2 ± 13.5 Aerobic: 62.5 ± 12.8 Advanced cancer NR Randomized pre-test post-test pilot study. Resistance versus aerobic exercise ( n = 66) Short Physical Performance Battery (SPPBF) for functional mobility VAS Resistance, aerobic, and flexibility 10 weeks; 2 times/week; customized (30–60 min) Non-significant decreases to pain scores were demonstrated in both groups between pre- and post-study Loudon 2014; Australia Intervention: 55.1 ± 2.5 Control: 60.5 ± 3.6 Breast Off treatment; completed 6 months prior Pilot, multi-centered randomized controlled trial using a parallel design. Wait list control group ( n = 28) Effect of yoga on lymphedema VAS Yoga: resistance, flexibility 12 weeks; session daily; 90 min There was no significant change to pain scores between groups McNeely 2004; Canada Intervention: 60 ± 7.4 Control: 61 ± 8.4 Head and neck NR Prospective pilot randomized controlled trial. Usual care control group ( n = 20) Recruitment, completion, adherence rate SPADI Resistance 12 weeks; 3 times/week; duration NS Significant improvements in pain scores and total shoulder pain and disability were found in the intervention versus control group McNeely 2008; Canada Intervention: 53 Control: 57 Head and neck Off treatment — exact time from surgery was 2–180 months Randomized controlled trial. Progressive resistance (intervention) versus standardized therapeutic exercise ( n = 52) Shoulder Pain and Disability Index (SPADI) SPADI pain subscale Resistance 12 weeks; 2–3 sessions; duration NR Intervention group had significantly improved shoulder pain and disability compared to control group Mijwel 2018; Sweden Resistance plus HITT: 52.7 ± 10.3 HITT: 54.4 ± 10.3 Usual care: 52.6 ± 10.2 Breast On treatment; adjuvant chemo, specifically anthracyclines, taxanes, or combination Randomized controlled trial. Resistance and HITT versus HITT versus usual care ( n = 240) Cancer-related fatigue EORTC-QLQ-C30 HITT aerobic, resistance 16 weeks; 2 times/week; 60 min Pain improved significantly in HITT group compared to usual care at 16 weeks Moller 2020; Denmark NR Breast Off treatment; at onset of adjuvant chemotherapy Single-blinded two-center randomized controlled trial. Hospital-based group exercise versus home-based pedometer ( n = 153) Maximum oxygen uptake —VO2peak EORTC QLQ-C30 pain subscale Aerobic 12 weeks; 5 times/week; 30 min Positive cardiorespiratory fitness responders had improved clinical effects on pain compared to negative responders; however, there were no statistically significant differences between groups or over time Nyrop 2017; USA Intervention: 63.3 ± 8.3 Control: 64.4 ± 9.7 Breast On treatment Randomized controlled trial. Wait list control ( n = 62) Engagement in walking (minutes per week), joint pain/symptoms, and adherence to AI therapy VAS and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Walking: aerobic 6 weeks; 150 min/week Pain severity declined more in the intervention group versus the control group on both WOMAC and VAS; however, the changes were not statistically significant Odynets 2018; Ukraine NR Breast Off treatment; after mastectomy Randomized 3-arm controlled trial. Water-based aerobic exercise plus land-based aerobics (group A) versus swimming plus Pilates (group B) versus yoga plus stretching (group C) ( n = 115) Post-mastectomy pain VAS and McGill Pain Questionnaire Aerobic, flexibility 1 year; 3 times/week; 60 min All groups had reductions in pain over the 1-year time period. Significant differences between study groups at 6 months with group A having lower pain scores than groups B and C. At 1 year, group C continued to have higher pain that the other two groups Park 2017; Japan Intervention: 54.78 ± 3.42 Control: 52.48 ± 5.57 Breast Off treatment Single blind randomized controlled trial. Usual care control group ( n = 69) NR VAS Aerobic and resistance 4 weeks; 5 times/week; 60 min The intervention group had significant improvements to pain compared to the control group Pasyar 2019; Iran Intervention: 51.6 ± 10.56 Control: 51.8 ± 11.4 Breast Off treatment; at least 1 year post-surgery Pilot randomized controlled trial. Usual care control group ( n = 40) Quality of life and upper extremity edema volume EORTC QLQ-C30 pain subscale Yoga: flexibility 8 weeks; 3 times/week; duration NS No significant differences were observed between the groups with respect to pain at 4 and 8 weeks Paulo 2019; Brazil Intervention: 63.2 ± 7.1 Control: 66.6 ± 9.6 Breast On treatment; AI therapy Randomized controlled trial. Control group participated in active stretching and relaxation ( n = 36) QOL EORTC QLQ-C30 pain subscale Resistance and aerobic 9 months; 3 times/week; 70 min Intervention group experienced significant decreases in pain symptoms at 9 months compared to the control group Peppone 2015; USA Intervention: 55.1 ± 1.24 Control: 53.2 ± 0.9 Breast Off treatment; 2–24 months post-treatment. On hormonal therapy Phase II/III randomized controlled trial. Wait list control ( n = 167) Sleep quality University of Rochester Cancer Center symptom inventory, FACT — fatigue subscale, Multi-dimensional Fatigue Symptom Inventory Short Form Yoga: flexibility 4 weeks; 2 times/week; 75 min Intervention group demonstrated significantly greater reductions in musculoskeletal symptoms including pain compared to control group Porter 2019; USA Intervention: 56.3 ± 11.6 Control: 59.4 ± 11.3 Metastatic breast On treatment Feasibility, randomized controlled trial. Control group was a support group ( n = 63) Feasibility and acceptability BPI-SF Yoga: flexibility 8 weeks; once/week; 120 min Little change over time in the outcomes for participants in either condition Reis 2018; Brazil Intervention: 47.6 ± 7.6 Control: 45.8 ± 8.1 Breast On treatment; chemotherapy, radiation therapy, clinical observation Pilot randomized controlled trial. Usual care control group ( n = 31) Pain (BPI) BPI, validated for Brazilian Portuguese Aerobic, resistance, and flexibility 12 weeks; 3 sessions for aerobic + resistance and 2 sessions for flexibility; 60-min aerobic + resistance and 15 min for flexibility Patients in the intervention displayed a significant reduction in total pain points, pain intensity, and pain interference compared to control Rief 2014; Germany Intervention: 61.3 ± 10.1 Control: 64.1 ± 10.9 Tumor diagnosis with spinal bone metastasis On treatment; radiation therapy Randomized controlled trial. Control group underwent respiration exercise and “hot roll” treatments ( n = 60) Feasibility VAS Resistance 12 weeks; sessions were on treatment days; 45 min Pain score significantly improved for the intervention group compared to the control group at 3 months Sohal 2020; India NR Breast Off treatment; radical mastectomy with chemotherapy or radiation therapy Interventional study. Usual care control group received bilateral exercise ( n = 20) Shoulder pain and disability, manual muscle testing, and ROM SPADI Resistance 6 months; 5 times/week; 60 min Significant improvements in pain for usual care control group (bilateral exercise) compared to intervention group were demonstrated Sprave 2019; Germany Intervention: 62.1 ± 8.8 Control: 61.1 ± 8.5 Cancer of the thoracolumbar segments On treatment; palliative radiation therapy Feasibility, randomized controlled trial. Control group received muscle relaxation therapy ( n = 60) Feasibility of isometric exercise in unstable vertebral bony metastases VAS Resistance 3 months; daily for RT then 3 times/week; 15 min No difference in pain was noted between groups after 3 and 6 months Steindorf 2014; Germany Intervention: 55.2 Control: 56.4 Breast On treatment; scheduled to receive radiation therapy Randomized controlled trial. Control group received relaxation therapy ( n = 160) Fatigue Standardized questionnaire, EORTC-QLQ-30 Resistance 12 weeks; 2 times/week; 60 min Significant improvement in pain score demonstrated in intervention versus control group. Effect sizes were small Stigt 2013; Netherlands Intervention: 63.6 ± 10.2 Control: 63.2 ± 10.3 Lung Off treatment Randomized controlled trial. Usual care control group ( n = 49) QOL Dutch version of the McGill Pain Questionnaire (MPQ-DLV) Aerobic, resistance 12 weeks; 2 times/week; duration NS Both groups had decreased pain over time; however, the intervention group reported significantly more pain at 3 and 6 months compared to control group Su 2017; Taiwan Outpatient: 48.89 ± 10.46 Home-based: 48.44 ± 9.84 Head and neck On treatment; receiving surgical intervention Randomized controlled trial. Home-based exercise group versus outpatient exercise group ( n = 37) QOL, FACT–Head and Neck VAS Aerobic, resistance, flexibility 12 weeks; aerobic = 5 × /week, anaerobic = 2 × /week, flexibility = 2 × /day; 60 h/week No significant differences in shoulder pain between groups Tang 2010; Taiwan Intervention: 47.4 ± 10.1 Control: 56.4 ± 12.4 Various Variable Randomized controlled trial. Usual care control group ( n = 71) Sleep quality and QoL Subscale on the SF-36 Walking: aerobic 8 weeks; 3 times/week; 30 min Pain improved in those who had improved sleep quality Tenconi 2021; Italy Intervention: 66 ± 10.6 Control: 67.8 ± 10.8 Lung On treatment; undergoing lung resection Single center, unblinded, 1:1 randomized controlled trial with two parallel arms. Usual care control group ( n = 140) Exercise tolerance NR Aerobic, resistance 14 pre-operative sessions and 39 post-operative There was no significant improvement in pain Van Waart 2015; Netherlands Home based: 50.5 ± 10.0Moderate to high intensity: 49.9 ± 8.4 Control: 51.6 ± 8.8 Breast Off treatment Randomized controlled multicenter trial. Home-based exercise versus moderate- to high-intensity aerobic and resistance exercise versus usual care ( n = 230) Cardiorespiratory fitness, muscle strength, and fatigue NR Aerobic, resistance Variable intervention time based on chemotherapy cycles; 5 times/week; 30 min Both intervention groups reported significantly less pain than the usual care (control) group Yagli 2015; Turkey Intervention: 68.5 ± 6.2 Control: 68.9 ± 2.9 Breast Off treatment; 6 months post-chemotherapy NR ( n = 20) NR Subscale on the Turkish version of the Nottingham Health Profile Yoga: flexibility 8 weeks; 60 min/week No difference observed between groups Yeo 2012; USA Intervention: 66 Control: 67 Pancreas and peri-ampullary Off treatment 2-group, prospective randomized controlled trial. Usual care control group ( n = 102) Fatigue Fatigue and Pain Visual Analog Scale (FPAS) Walking: aerobic 12 weeks; 3–5 times/week; 90–150 min Pain improved in both groups over time. There were no significant differences between the groups post-intervention NR = not reported. Bolded studies are those included in the meta-analysis

Exercise interventions were categorized based on American College of Sports Medicine (ACSM) [ 108 ] categories of aerobic, resistance, or flexibility. Thirty-three studies focused on only one category of exercises (e.g., aerobic only), whereas 43 studies included a combination of exercises (e.g., aerobic, strength, and flexibility). Forty-six studies reported only supervised exercise sessions, with 16 studies reporting a combination of supervised and unsupervised sessions, and 14 studies either reporting unsupervised sessions or were unclear about the supervision. Most of the supervised sessions were conducted in a public facility, whereas unsupervised exercise sessions were conducted at home. All supervised sessions were conducted by certified professionals (e.g., registered kinesiologists, clinical exercise physiologists, certified personal trainers), physiotherapists, physical therapists/assistants, physical education professionals, or yoga instructors. Details regarding study specific training for the certified exercise professionals were rarely provided. The exercise sessions ranged from one session per week to five sessions per week, with a total duration of 15 to 120 min. The length of the exercise interventions lasted anywhere from 3 weeks to 2 years.

Meta-analysis

Ten studies were included in the meta-analyses (data from 631 participants), and the observed SMDs ranged from − 1.99 to − 0.09 [ 18 , 41 , 45 , 51 , 57 , 58 , 69 , 85 , 89 , 91 ]. The estimated average SMD based on the random-effect model was g = − 0.73 (95% CI: − 1.16 to − 0.30; Fig. 2 ) which differed significantly from zero ( z = − 3.29; p = 0.001). Measures of between-study variance (tau 2 = 0.41), inconsistency across studies ( I 2 = 83.9% [71.9–90.7%]), and variability in the effect estimate due to heterogeneity rather than sampling error (Cochran’s Q = 55.78, p < 0.001) point towards considerable heterogeneity. In the random-effect model, the 95% CI contains highly probable values for the mean effect but does not provide information on the range of treatment effects that are likely to be seen in similar settings; for example, in the next study or in the next patient an exercise professional intends to treat [ 29 ]. The 95% prediction interval crosses zero (− 2.29 to 0.83; Fig. 2 ). Although larger effects in the direction of benefit (decreased pain) are included, values above zero (increased pain) are also included and are large enough to be clinically meaningful in this context. Neither Begg’s rank test (− 0.47; p = 0.073) or Egger’s test (− 1.29; p = 0.198) indicated funnel plot asymmetry. Fig. 2 Forest plot for standardized mean difference (SMD) effect size for post-intervention pain. The grey squares represent the SMD, and the left and right extremes of the squares represent the corresponding 95% CI. The grey diamond represents the overall effect, and the bold black line represents the prediction interval, derived from the SMD and 95% CI

Risk of bias

Figure 3 summarizes the ROB in the studies eligible for meta-analysis. For the ROB resulting from the randomization process (domain 1), 60% were at low risk of bias, and 40% raised some concerns due to incomplete reporting. For risk of bias due to deviations from the intended interventions (effect of assignment to the intervention; domain 2), half of the studies were at low risk of bias, and half raised some concerns due to a lack of reporting or due to possible contamination (an increase in physical activity levels in the comparator arm that was probably due to the context of the trial). For pain and other patient-reported outcomes, participants are outcome assessors. Pain is potentially influenced by the knowledge of the intervention in the context of exercise versus usual care. In this context, we considered that the exercise intervention might come with prior beliefs that it would be more beneficial than the comparator. Conversely, we also considered that the exercise intervention might come with prior beliefs that exercise would worsen pain. However, this is unlikely given the stated purposes of the included studies (towards the benefits of exercise). Based on this, following the ROB2 algorithm for domain 4 (risk of bias in the measurement of the outcome), all studies would have been rated as high risk of bias. We decided to override this for all similar decisions within the context of this review, leading to a less severe ROB2 judgement of “some concerns” for 9 studies. For domain 5, all studies raised some concerns due to risk of bias in the selection of the reported results, which is a known issue in the exercise oncology literature [ 109 ]. Only 4 of these RCTs referenced a clinical trial registration [ 18 , 41 , 69 , 89 ]. However, of these, only 2 studies were prospectively registered [ 69 , 89 ]. For the other 6 studies, we were unable to find trial registrations. Fig. 3 Summary risk of bias using the RoB2

Using GRADE, the certainty of the meta-analytic evidence (the extent of confidence the estimate of effect is correct) was considered low certainty (i.e., further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate) [ 32 ]. In summary, the evidence was downgraded by one level due to the overall assessment of some concerns for every study and some concerns in at least one domain in addition to domain 4 (risk of bias in the measurement of the outcome). In many cases, judgements were not possible due to insufficient reporting of important methodological details. We also considered the lack of prospective registration in 8 of the studies. Combined, this was sufficient to lower confidence in the estimate of effect. We did not strongly suspect publication bias in the studies eligible for the meta-analysis (but note that this assessment does not extend to studies eligible for narrative synthesis). We judged the evidence to have no serious indirectness, because despite variability, studies compared exercise interventions to cancer populations, and all studies used a self-report measure of pain as the primary outcome. For continuous outcomes such as pain, the decision to downgrade certainty because of imprecision is based on whether a recommendation of exercise for CRP would be altered if the lower versus the upper boundary of the CI represented the true underlying effect. The lower boundary is − 0.30, a modest effect size that may or may not be clinically important. Considering that the sample size in the meta-analysis ( n = 631) meets the optimal information size criterion, we did not downgrade due to imprecision [ 33 ]. In the assessment of inconsistency, we considered wide variation in point estimates across studies (− 1.99 to − 0.09; Fig. 2 ) and statistical criteria indicating considerable heterogeneity. We considered that differences in interventions may explain some inconsistency, so the certainty was downgraded by one level [ 32 , 33 ].

Discussion

Exercise for managing pain in adults living with and beyond cancer is a growing outcome of interest in the area of exercise oncology [ 110 ]. Evidence is needed to guide the use of multimodal pain management strategies (including exercise) given the growing prevalence of those living and beyond cancer [ 111 ] and the ongoing opioid crisis and subsequent need to judiciously prescribe opioids [ 112 ]. Thus, the objective of this review was to determine the benefits of exercise in pain management in adults living with and beyond cancer.

The findings from our meta-analysis demonstrated a decrease in pain scores in those who exercised. There was considerable heterogeneity in the studies included in the meta-analysis, which is consistent with much of the literature in exercise oncology [ 11 ]. Although the estimated average SMD shows benefits of exercise for CRP, the overall effect prediction interval was large, indicating that in some settings, exercise will have no effect or may lead to worse pain. This is unsurprising, as similar meta-analytic findings have been demonstrated for post-treatment cancer-related fatigue [ 113 ]. This reinforces the understanding that exercise must be tailored to the individual in order to optimize potential benefits [ 11 ]. In addition, the certainty of the evidence was considered low due to concerns across multiple domains, as well as heterogeneity. While more studies were included in this review than originally anticipated, a pertinent finding is the lack of high-quality trials examining the role of exercise for pain as a primary outcome and a lack of registering and reporting of study protocols. In addition, the MCID was only reported for 10 studies. MCID is an important reporting criterion in clinical trials as it aids in understanding the magnitude of effect [ 114 ].

There are several other factors that should be considered when determining the role of exercise for CRP. Firstly, there is a potential net benefit of exercise, considering the broad health benefits for people living with and beyond cancer [ 10 , 12 ], coupled with the low risk of harms [ 10 , 12 ]. Regular monitoring of pain through simple momentary (during or after an exercise session) or weekly (throughout an intervention) ratings would help identify individual responses and ensure that exercise does not lead to worsening pain. Overall, exercise is acceptable to both healthcare providers and patients, and feasible in multiple settings [ 11 , 12 ]. Lastly, equity should be considered when considering the role of exercise for CRP. For example, pain is often underrecognized in women [ 115 ] and people of color [ 116 ]. Specific populations are also more likely to be profiled as drug-seeking [ 117 , 118 ], therefore more likely to have pain that is untreated. Efforts should thus be made to support access to exercise for all individuals living with and beyond cancer, including underserved populations such as ethnic/racial minorities, adolescent and young adults, and those living in rural or remote locations. One means of supporting access to evidence-based exercise programming is offering hybrid and/or virtual options which have grown since the start of the COVID-19 pandemic [ 119 ]. Virtual exercise that is supervised has been shown to be feasible and should be offered to the people living with cancer who are immunocompromised, have disabilities, have travel barriers, or for those living outside of urban centers where exercise oncology resources are usually located [ 120 ].

There is theoretical evidence that exercise should be effective for pain management. From a physiologic perspective, exercise increases endorphins which have an analgesic effect [ 121 ]. Exercise also prevents joint stiffness and muscle tightness, improves blood circulation, and improves muscle strength and function [ 121 ], all of which may help mitigate pain in cancer patients. In chronic pain populations, tailored exercise programming based on the etiology of the pain (e.g., neuropathic, nociceptive, neuroplastic) and functional capacity are the mainstay of multimodal pain management strategies [ 122 ]. Researchers should consider testing tailored exercise interventions based on FITT principles to address specific types and areas of cancer pain (e.g., managing shoulder pain/stiffness post head and neck cancer surgery with strengthening and stretching) to add to the evidence for this type of intervention.

Other types of behavioral interventions have been shown to be effective for managing cancer-related pain. For example, findings from a study examining a behavioral pain management intervention for individuals living with and beyond colorectal cancer found that it was feasible to deliver telephone-based coping skills training, with participants reporting increased self-efficacy for pain management [ 123 ]. Another intervention that delivered progressive muscle relaxation and interactive guided imagery for pain management in terminal cancer patients found improvements in both intensity and pain-related distress [ 124 ]. Participant perspectives of guided imagery and progressive muscle relaxation for CRP have also been explored, with qualitative results showing both improved perceptions of pain along with self-reported clinically significant changes in pain [ 125 ]. Given that exercise is a type of behavioral intervention, the present systematic review adds further evidence that tailored exercise interventions should be evaluated in the future.

Limitations

CRP should be distinguished from pain caused by comorbid disease [ 4 ]. This nuance was rarely considered in eligible articles and is therefore not considered in this review. Another limitation is that we did not extract and inspect pain severity at baseline. It was rarely an inclusion criterion for eligible studies, and therefore, it may have been mild at baseline, limiting any reported impact on pain changes from the exercise intervention. The main limitation of the meta-analysis is that studies rarely reported follow-up data, and therefore, this was not analyzed in the current review. Currently, the effect of exercise on CRP during a longer term follow-up beyond the intervention is unknown and must be investigated in future work.

Clinical implications and future research

Cancer pain is highly prevalent in those living with and beyond cancer and can impact many domains related to quality of life [ 1 , 2 ]. While pharmacologic therapy (opioids, non-opioids, and other adjuvant medications) is the main treatment for cancer pain, there is a growing need for multimodal pain management strategies. Cancer patients may not want side effects or risks associated with long-term pharmacologic therapy [ 126 , 127 ]. In addition, cancer care clinicians recognize the importance of limiting opioid prescriptions and the need to treat the psychological (e.g., existential suffering), cognitive, and behavioral dimensions of pain [ 126 , 127 ]. While our review demonstrates that exercise may be beneficial in reducing cancer pain, the heterogeneity of studies and, thus, grade of evidence was low. An interdisciplinary team approach to pain management based on tailored patient-centered care [ 126 ], where exercise is viewed as an important component of the cancer care continuum, should be considered.

To strengthen the evidence the following future research directions should be considered. Future research exploring the role of exercise for pain as a primary outcome in individuals living with and beyond cancer is needed. Further, based on the findings from this review, much of the research to date exploring the role of exercise for CRP has been in breast cancer. Future work should include underserved tumor groups (e.g., neuro-oncology or those living with metastatic disease). Importantly, researchers should aim to meet basic standards for clinical trials (e.g., prospective registration) in future powered RCTs for the effect of exercise for CRP, given known issues with outcome reporting bias and a bias towards “positive” results in health research, kinesiology, and exercise oncology specifically, [ 128 , 129 ]. Finally, studies using implementation science frameworks to determine how best to integrate clinical pathways for referrals to exercise professional within cancer care organizations [ 10 ] are needed. All are necessary to support clinical decision-making and inform evidence-based clinical practice guidelines.

Supplementary Information

Below is the link to the electronic supplementary material. Supplementary file1 (DOCX 14 KB)

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Author contribution

Benny Rana: investigation, validation, writing — review and editing. Mannat Bansal: investigation, validation, writing — review and editing. Julia Theresa Duan: investigation, validation, writing — review and editing. Rosemary Twomey: conceptualization, methodology, investigation, formal analysis, validation, data curation, writing — original draft. Susan Nicole Culos-Reed and Colleen Cuthbert: conceptualization, supervision, project administration, writing — review and editing. Tana Dhruva: investigation, validation, writing — review and editing. Veronica Livingston: investigation, validation, writing — review and editing.

Data Availability

All supplementary materials, data, and code are openly available at https://osf.io/as2eh/ .

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Ethics approval and patient consent were not needed for this systematic review and meta-analysis.

Conflict of interest

The authors declare no competing interests.

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