Exercise and quality of life in cancer

Carmn Fiuza-Lus *,Pro L.Valnzulab ,Aljanro Santos-Lozano ,Ana Ruiz-Casao ,Aljanro Luia

a Physical Activity and Health Research Group(PaHerg),Research Institute of Hospital 12 de Octubre(‘i+12’),Madrid 28041,Spain

b Department of Systems Biology,University of Alcal′a,Madrid 28871,Spain

c i+HeALTH Research Group,Department of Health Sciences,European University Miguel de Cervantes,Valladolid 47012,Spain

d Department of Medical Oncology,Hospital Universitario Puerta de Hierro Majadahonda,Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana(IDIPHISA),Madrid 28220,Spain

e Faculty of Sport Sciences,Universidad Europea de Madrid,Madrid 28670,Spain

Historically,patients with cancer were told to avoid physical exertion.This dogma has changed over the last 2 decades,with an exponential growth in the number of studies showing not only the safety,but also the benefits of regular physical activity/exercise in the cancer continuum,notably for attenuating treatment-related toxicities and side effects.Thus,the paradigm has now shifted to the concept of“exercise is medicine”,with leading world experts advocating that “all people living with and beyond cancer can be as active as is possible for them”.1

The initial work on exercise implementation during cancer treatment is attributed to Winningham et al.,2who in the late eighties reported the benefits of 10-to 12-week supervised aerobic exercise training on the body composition and cardiorespiratory fitness3of women with breast cancer undergoing adjuvant chemotherapy,as well as on an important component of health-related quality of life (HRQoL) in this clinical context:patient reports of nausea.4The results of these studies were part of Winningham’s doctoral thesis(completed in 1983 at Ohio State University),which was actually inspired by the book entitledDo Not Go Gentle,by Herbert Howe.5Howe,a doctoral student at Harvard,decided to start exercising while undergoing treatment for fibrosarcoma: “Cancer transformed my life into a sports analogy.As I ran faster and further,I realized I could endure more chemotherapy”.5Subsequent landmark research was done by Dimeo et al.,6who in 1997 published the first randomized controlled trial showing that exercise implementation can attenuate some toxicities associated with high-dose chemotherapy in adult patients of both sexes.

A myriad of studies have been published in the current millennium and,as a result,several national and international organizations(notably,the American College of Sports Medicine) have launched exercise recommendations for patients living with and beyond cancer.In the last American College of Sports Medicine roundtable on exercise and cancer,an expert panel concluded that “there is sufficient evidence to support the efficacy of specific doses of exercise training to address cancer-related health outcomes”,including not only fatigue,physical function,anxiety,or depressive symptoms,but also HRQoL.7Combined moderate-intensity aerobic and resistance exercise performed twice or thrice a week for 12 weeks,especially if sessions are supervised,improves HRQoL both during and after treatment,beyond the gains obtained with aerobic or resistance training alone.7As noted by the guidelines’authors,however,HRQoL is a construct that encompasses many factors and may have a variable response across individual domains,with greater improvements if the primary outcome is the physical functioning domain.It was also recognized that the majority of available literature is focused on the most common malignancies,notably early stage breast cancer and prostate cancers,which limits generalizability to other—more aggressive or advanced—tumors.To this extent,the recent network meta-analysis by Li et al.8on exercise and HRQoL in the context of digestive system cancers (DSCs),which are among the most burdensome tumors,is topical.

Li et al.8analyzed which is the optimal exercise type/duration to improve HRQoL—including the general,physical,and mental health domains,as well as role function—in patients with DSC.Most studies (totaln=2558 participants) were done on colorectal cancer(40.6%),followed by colon and esophageal cancers (12.5% each),rectal cancer (9.38%),pancreatic and liver tumors (6.25% each),and mixed DSCs (12.5%).The results indicated that short-term (＜12 weeks) aerobic exercise had the highest probability to enhance patients’ HRQoL,improving general health (standard mean difference between exercise and control intervention=0.66;95% credible interval:0.05-1.39).It must be noted,nonetheless,that unclear effects(with the 95% credible interval crossing 0) were observed for other domains such as mental health or role function.A somewhat counterintuitive finding that deserves further research was that long-term resistance exercise (＞12 weeks) was linked to lower general health,physical health,and role function,which prompted the authors to recommend that this exercise modality should be adopted cautiously in patients with DSCs.

Some caveats must be noted in the Li et al.’s study8that might compromise its internal validity,notably the fact of combining all DSCs.DSCs can differ considerably with regard to the nature of the tumors themselves (e.g.,colorectalvs.pancreas cancer) and their expected effect on patients’ HRQoL (e.g.,colostomyvs.pancreatectomy).The clinical scenario (metastaticvs.nonmetastatic cancer;before surgeryvs.after surgery)was not considered and more information would have been desirable on other major burdens in the context of DSC treatment (notably neuropathies),which nonetheless should not affect the main study results.In turn,a major strength of the meta-analysis is the important question addressed by the authors.Indeed,HRQoL has gained considerable attention in cancer,being a prognostic indicator (independent of other “traditional” biomedical parameters),9and a key patientreported outcome—with growing evidence that the collection of patient-reported outcomes can enhance the quality of care received by patients and should be implemented in clinical practice.10Notably,improving the HRQoL of patients and survivors,known as“A Better Life for Cancer Patients Initiative” is 1 of the 4 key action areas of the“Europe’s Beating Cancer Plan”(https://health.ec.europa.eu/system/files/2022-02/eu_cancer-plan_en_0.pdf).

More research should focus on the biological mechanisms underlying exercise benefits in the wellbeing of patients with cancer as well as on the effects of exercise in the context of highly advanced DSCs.In addition,the actual clinical significance of exercise-induced improvements in HRQoL and its different domains—which on average were of small to medium magnitude in the Li et al.meta-analysis—remains to be clearly established.8

Acknowledgments

Research by PLV and CFL is supported by a Sara Borrell(CD21/00138) and Miguel Servet (CP18/00034) postdoctoral contracts,respectively,granted by Instituto de Salud Carlos III.AL and CFL are funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Alejandro Lucia,Grant No.PI18/00139;Carmen Fiuza-Luces,Grant No.PI20/00645)and by“the Wereld Kanker Onderzoek Fonds”(WKOF),as part of the World Cancer Research Fund International grant program(Grant No.IIG_FULL_2021_007).

Authors’contributions

AL and CFL drafted the manuscript with the help of PLV,ASL,and ARC.All authors have participated in conception and literature search.All authors have read and approved the final version of the manuscript,and agree with the order of presentation of the authors.

Competing interests

The authors declare that they have no competing interests.