Exercise Therapy in Oncology

The Impact on Quality of Life and Side Effects

Background: The diagnosis and treatment of cancer are highly stressful. Exercise therapy is often used to mitigate the adverse effects of treatment. But how good is the evidence base, and what has changed in recent years? In this narrative review, we present the current data and what it implies for the care of adults with cancer.

Methods: This review is based on data from meta-analyses and systematic reviews concerning 16 relevant clinical endpoints (outcomes) of exercise therapy for cancer patients.

Results: The literature evaluated for this paper reveals that targeted exercise therapy is feasible and safe under appropriate supervision. It is highly effective for improving eight endpoints (anxiety, depression, fatigue, quality of life, physical function, secondary lymphedema after breast cancer, urinary incontinence, post-mastectomy pain syndrome in breast cancer) and may also have a beneficial effect on sleep quality, cardiotoxicity, and cognitive function. Less conclusive studies are currently available with respect to chemotherapy-induced polyneuropathy, nausea/vomiting, and bone health. There is currently insufficient data to suggest any benefit with respect to sexual function and risk factors for falling.

Conclusion: The data shows that exercise therapy for cancer patients is safe and has manifold effects on selected clinically relevant parameters. Further studies should be performed regarding the possible utility of exercise therapy against treatment-related side effects for which the evidence is currently insufficient. On the basis of the currently available and already existing recommendations, quality-assured exercise therapy can be recommended to cancer patients suffering from a wide range of neoplastic conditions.

In Germany, about half a million persons receive a cancer diagnosis every year. According to the Robert Koch-Institute, 232 720 women and 265 170 men were diagnosed with cancer in 2018 (1). Cancer patients’ survival rates have substantially improved as a result of advances in multimodal treatment options (2). Almost two thirds of those affected survive beyond 5 years after the initial diagnosis (1). Simultaneously, however, somatic and psychological acute sequelae occur, as well as late and long-term sequelae, which can mean a notably worsened quality of life (3).

Potential biological mechanisms

Preclinical studies have shown the effect of exercise on blood parameters such as circulating immune cells, sexual hormones, insulin and glucose concentrations, and lipid metabolism (4). Studies in humans evaluating direct effects on the tumor micromilieu in vivo are, however, lacking. The influence is complex: a multitude of specific biological effects in patients with cancer combine and interact (Figure 1). Many mechanistic questions require further research and clarification—especially also in primary tumor tissue and in clinical-translational studies.

Figure 1

Mode/mechanism of action of exercise therapy in oncology and selected potential mechanisms

Exercise therapy as a supportive measure

In recent years, research has led to a better understanding of the positive and multidimensional effects of exercise therapy in the oncology setting. Study results have confirmed safe use in terms of feasibility and especially in the prevention and reduction of different therapy-relevant adverse effects and improvements to quality of life (Figure 2) (5). This paper investigates how effective exercise therapy actually is as regards individual adverse effects of the cancer disease and therapy and where its currents limitations are.

Figure 2

Oncological exercise therapy in the sectors

Methods

We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for internationally published key publications on oncological exercise therapy that were published between (and including) January 2018 through April 2023. The literature search was reviewed by two independent reviewers (F.T.B., M.L.). The selection criteria and all identified review articles are listed in the eTable.

eTable

Relevant clinical endpoints taking into account selected meta-analyses and systematic reviews

We identified 16 relevant endpoints by clinical relevance and the expected therapeutic benefit of exercise therapy. Each of the 16 endpoints was allocated a recent key publication—a meta-analysis in preference, and where none existed, a systematic review.

The following is a list of the decisive characteristics of the quality criteria for the evidence:

• The topicality
• The number of subjects in the systematic reviews (n=≥/<150)
• The effect size (effect close to 0)
• The heterogeneity of the effects
• Further methodological characteristics (6).

This quality assessment differs from the often used risk of bias assessment.

Results

We describe the current clinically relevant endpoints of exercise therapy in the oncological setting. Table 1 and the eTable show a detailed overview of the results of this narrative review.

Table 1

Relevant clinical endpoints taking into account selected meta-analyses and systematic reviews

Anxiety and depression

A meta-analysis of the reduction of anxiety (standardized mean difference [SMD]: 0.26, 95% confidence interval [011; 0.42]) and depression (SMD: 0.49 [0.27; 0.72]) showed effects for different forms of exercise of light to moderate intensity (endurance and strength/weight training) in patients with lung cancer (7). Of 36 included studies, 23 were of high quality.

Fatigue symptoms

Furthermore, studies included in a systematic review indicated that an adapted training program, consisting of endurance training or combined endurance and strength/weight training, reduced symptoms of fatigue (SMD: −0.33 [−0.43; –0.23] during and after cancer treatment. This applied particularly to women with breast cancer (SMD: −0.36 [−0.57; −0.15]) or men with prostate cancer (SMD: −0.34 [−0.45; −0.22]) (8).

Quality of life

A meta-analysis of 79 randomized controlled trials (RCTs) described that physical activity improved health related quality of life (weighted mean difference [WMD]: 5.94 [2.64; 9.24]) (9).

Secondary lymphedema after breast cancer

A review of six RCTs showed a significant reduction in cancer related lymphedema as a result of strength/weight training (L-Dex score −1.10 [−2.19; –0.01]). Negative effects of strength training on secondary lymphedema were not identified (10).

Physical functioning

A meta-analysis of 44 RCTs confirmed the effect of controlled sports therapy intervention on physical functioning (improvements to subjectively assessed performance). Exercise showed moderate effects on the primary results of physical functioning (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ C30], Short Form [SF]-36 [SF-36], Functional Assessment of Cancer Therapy – Breast [FACT-B]; SMD: 0.52 [0.38; 0.66]) (11). Because of substantial heterogeneity (79.2%) the level of certainty of the results in this review was downgraded.

Urinary incontinence

According to a recent meta-analysis including 20 RCTs, targeted sphincter training reduced the risk of urinary incontinence in prostate cancer patients after prostatectomy. Compared with no training, sphincter training resulted in a risk reduction of 12–25% regarding the regression of urinary incontinence three months (20% [12; 28]), three to six months (25% [18;33]), and more than six months (12% [4; 20]) after prostatectomy (12).

Post-mastectomy pain syndrome in breast cancer

A meta-analysis including six RCTs described a significant reduction in pain (SMD: −1.00 [−1.48; −0.52]) in women with shoulder pain associated with a mastectomy (13), as a result of exercise therapy.

Sleep quality

There are indications that endurance training or combined endurance and strength/weight training can improve the sleep quality in women with breast cancer. Studies with a larger sample size are required to confirm this (14).

Cognitive functioning

To date, few studies have investigated whether exercise training improves cognitive functioning in patients with cancer. The combined results of a meta-analysis including 10 RCTs showed an overall positive effect of exercise on cognitive functioning (Hedges’ g: 0.35 [0.19; 0.52]) in men with prostate cancer compared with a control group.

Cardiotoxicity

A combination of endurance and strength/weight training has the potential to significantly improve cardiorespiratory fitness (VO₂max) as well as left atrial and left ventricular diastolic function (E/A ratio) in women with breast cancer who are being treated with anthracyclines or trastuzumab. This helps alleviate cardiotoxic adverse effects of the treatment (16).

Bone health

Strength and endurance training, combined with impact training (targeted thrusts and pushes, such as double leg hops in place, single leg jumps, and skipping) improved bone mineral density of the hip and spine. Such effects seem more pronounced in women than in men (17). In spite of promising results it needs to be borne in mind that the assessment is currently strongly influenced by the results of premenopausal women from the working group of Saarto (18).

Chemotherapy induced peripheral neuropathy

Some studies indicate that combined training improves physical functioning (balance control and muscle strength), neuropathic pain, and quality of life in patients who are experiencing cancer and chemotherapy induced peripheral neuropathy (CIPN). Sensory functioning and reflex status, however, remain unaffected (19).

Nausea/vomiting

A meta-analysis by Nakano et al, which included nine RCTs and a mixed oncological disease spectrum showed an advantage in favor of an exercise therapy intervention to prevent nausea and vomiting (20) that didn’t reach significance (p=0.09). A more recent meta-analysis by Chen et al focused exclusively on patients with breast cancer and included eight RCTs and described as significant advantage of targeted physical exercise for the outcome nausea and vomiting (21).

Sexual functioning

Regarding sexual dysfunction as an adverse effect in urological or gynecological tumors, data are lacking to assess the effectiveness of sport and exercise training in the context of these impairments (22).

Risk factors for falls

A selected systematic review including 11 studies showed that exercise training improves important factors of influence to prevent falls in patients with cancer. These factors of influence include—among others—muscle weakness, balance impairments, and restricted mobility. It is not known whether exercise treatment can reduce the rate of falls as such in persons with and after cancer disease (23).

Current exercise recommendations

Neither cancer specific kinds of sport nor interventions can be defined on a “once size fits all” basis; no general recommendation for certain types of sport can therefore be formulated.

In principle, moderate endurance training, such as walking quickly, cycling, or swimming, in combination with strength/weight exercises, has been found to be safe and easy to carry out. The American College of Sports Medicine (ACSM) recommends generally for cancer patients moderate to strenuous endurance training three times a week for at least 30 minutes over a time period of at least 8–12 weeks. The intensity imposed on patients can be guided and monitored by using the Borg scale (reference range: 6–20), which can be used to measure subjectively experienced exhaustion and dyspnea. The intensity should be at 12–13 (moderate strenuous). Furthermore, strength/weight training with 8–15 repetitions at 60% of the one repetition maximum (1-RM) should be undertaken twice a week. If a patient has a medically stated need for exercise therapy, supervised, quality assured sports therapy and/or physical therapy is recommended in addition to the named everyday activities. The content of exercise therapy is guided by the specific adverse effects and consider so called FITT (frequency, intensity, time, type) criteria. These criteria enable more targeted and effective therapy for the patients (24).

Nationwide information networks provide information on specific services for exercise therapy for adults—for example, the network OnkoAktiv. Billable, quality assured types of care—such as oncological training and exercise (OTT)—are in development and are being extended. In addition to targeted quality assured exercise therapy, keeping up daily activities is also recommended, as in the German clinical practice (S3) guideline for breast cancer (25). Even in 2010 patients with cancer were advised to avoid inactivity and sedentary behavior. The World Health Organization currently recommends this for persons with chronic diseases in general (26).

Contraindications and safety

Exercise therapy in oncology is considered safe and effective. But in principle, there is a risk of sports injuries, which means that undesirable events may occur. These are extremely rare and can be minimized by qualified instruction and monitoring of the exercise therapy. For this reason different specific health related components—such as heart disease, metastases, medication, and prior experiences with exercise should be borne in mind when developing and implementing a safe oncological therapeutic concept (Table 2).

Table 2

An approach to care recommendations for cancer patients to reduce exercise therapeutic undesirable events

According to Baumann and Schüle (27), the following are absolute contraindications to participating in exercise therapy:

• Severe infection
• Cardiovascular symptoms, impaired consciousness, vertigo/dizziness, severe nausea, vomiting
• Acute bleeds, severe pain
• Laboratory results: hemoglobin (Hb) <8g/dL with dizziness, thrombocyte counts <10 000/µL
• < 48 h after cardiotoxic chemotherapy no vigorous exercise.

Challenges to the practical implementation of exercise therapy studies

Because of lacking routine services for oncological exercise therapy, study related patient recruitment may be subject to positive selection—participants with a greater interest in exercise programs may be more prepared to participate in studies. Furthermore, insights from exercise studies with a high proportion of breast cancer patients are not immediately generalizable to other entities (28, 29).

To ensure the motivation for and adherence to participation in exercise therapy studies in all cancer patients, the following measures in the studies have been found to be effective on the basis of the authors’ own experiences:

• Education about and recommendation of physical activity by the treating medical staff
• Individual and supervised exercise therapy
• Shared decision making even when planning the therapeutic intervention
• Regular, mandatory appointments for adapting/ adjusting the therapy.

These measures led to up to 80% adherence in exercise studies (30).

Further limitations in conducting exercise therapy studies are the inability to blind participants when allocation them to groups as well as ethical considerations, which do not allow for ruling out or restricting physical training in the control group.

Discussion

This narrative review aims to provide an updated overview of the evidence supporting exercise therapy in the context of cancer specific effects and adverse effects.

As in the 2019 ACSM guidelines, the evidence level is high regarding the positive effect of targeted exercise therapy for anxiety, depression, fatigue, quality of life, secondary lymphedema after breast cancer, and physical functioning. The interpretation as “high level evidence” does, however, not meet the usual criteria for evidence, such as risk of bias analyses, which require blinding, for example. The reported prevalence of adverse effects is 10–30% and for fatigue up to 80% (31). An earlier Cochrane article from 2018 on this subject, especially in breast cancer, critically remarks that only a slight to moderate positive effect of exercise on quality of life was shown. These positive results should be interpreted with caution because of the low to moderate quality of the evidence, the heterogeneity of the interventions and event measurements, and the risk of bias in many studies (32).

Recent meta-analyses have shown a high degree of effectiveness of supervised sphincter training to prevent urinary incontinence, which occurred more rarely (12–25% risk difference). Because of the high prevalence of urinary incontinence as a long-term sequela it is of particular importance to translate this information and recommendation into clinical practice in a timely fashion. An additional innovation is that exercise therapy improves the severity of pain in women with breast cancer (post-mastectomy pain syndrome in breast cancer).

Potential evidence was formulated for cognitive functioning, cardiotoxicity, and sleep quality. Sleep quality has an important position in this as the prevalence of sleeplessness in cancer patients whose disease was newly diagnosed or recently treated was 30–75%. In advanced cancer, sleep quality is impaired up to 50% (33). Of note: fewer than five RCTs were available for the evaluation of cognitive functioning and cardiotoxicity; the results should therefore be interpreted with caution.

Exercise studies of chemotherapy induced peripheral neuropathy, falls, pain, and nausea were evaluated on the basis of limited or insufficient evidence. At this point in time, however, we identified a robust meta-analysis for women with breast cancer. This showed a positive effect of exercise therapy on nausea and vomiting. Possible explanations for why the data on nausea and vomiting are not clearer include optimized antiemetic treatment and changes to systemic therapy protocols over the years, but also the heterogeneity of the exercise programs.

Children and adolescents develop cancer disease in far fewer cases than adults (approximately 2200 cases in Germany per year) (34). The evidence of exercise therapy on cancer specific adverse effects is lower-level (35). Undesirable treatment effects often affect childhood cancer survivors their whole lifetime. For this reason, management of adverse effects, tolerability of treatment, quality of life, and consideration/prevention of acute and late sequelae are therefore of particular importance in this age group and are the subject of an individual S2K (consensus based) guideline (AWMF registry number 025–036).

Limitations

Limitations of this review are in particular the relevant key publication, which in part relate only to certain cancer entities and sexes, with the result that it was not possible to evaluate the evidence in a more differentiated manner. Furthermore, we note critically that we carried out a narrative review, not a systematic review. Overall, we were therefore able only to formulate limited conclusions regarding the evidence. A systematic literature search is currently being implemented in the development of the S3 (clinical practice) guideline for exercise therapy in cancer disease. This will enable more valid conclusions regarding the evidence (36).

Conclusions and outlook

Based on the current evidence and inclusion in S3 and S2K guidelines, nationwide healthcare structures should be created for exercise therapy measures in cancer patients in all age groups. Not only patients having medical treatment and rehabilitation should be considered but also long-term survivors. Additionally, further research is needed, especially into mechanisms, prehabilitation, and palliative medicine, so as to test the effectiveness of exercise therapy in these settings too. Similarly, therapy related adverse effects for which sufficient evidence is currently lacking should also be the subject of future studies.

Conflict of interest statement
FTB is a board member of the Deutscher Verband für Gesundheitssport und Sporttherapie (DVGS, the German association for health sports and exercise therapy).

ABE received honoraria for continuing medical education events for exercise instructors in the subject of sport and cancer from the Behinderten- und Rehabilitationsverband Bayern (BVS, the Bavarian disabled and rehabilitation sports association, reg. assoc.).

The remaining authors declare that no conflict of interest exists.

Manuscript received on 31 May 2022, revised version accepted on 19 February 2024.

Translated from the original German by Birte Twisselmann, PhD.

Corresponding author
Prof. Dr. sportwiss. Freerk T. Baumann
Universität zu Köln, Klinik I für Innere Medizin
Centrum für Integrierte Onkologie Aachen Bonn Köln Düsseldorf
Uniklinik Köln, CIO-Gebäude 70
Kerpenerstraße 62, 50937 Köln

Cite this as:
Baumann FT, Jensen W, Berling-Ernst A, Theurich S, Leitzmann M, Götte M: Exercise therapy in oncology—the impact on quality of life and side effects. Dtsch Arztebl Int 2024; 121: 331–7. DOI: 10.3238/arztebl.m2024.0038

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