Effects of Systemic Anticancer Treatment on Cardiorespiratory Fitness: A Systematic Review and Meta-Analysis

BACKGROUND Poor cardiorespiratory fitness (CRF) is associated with a higher symptom burden and an increased prevalence of long-term treatment-related cardiovascular disease risk factors in cancer survivors. However, the magnitude of systemic therapy-related CRF impairment remains unclear. OBJECTIVES The aim of this study was to evaluate the effects of systemic anticancer treatment on CRF and identify physiological determinants underpinning CRF impairment. METHODS A systematic literature search was performed in PubMed, Embase, CINAHL, SPORTDiscus, and the Cochrane Library. The primary endpoint was the change in CRF, measured by peak oxygen consumption (Vo(2peak)), from before to after systemic treatment. Secondary endpoints included post-treatment differences in Vo(2peak) between cancer survivors and noncancer control subjects, along with physiological determinants of Vo(2peak). Two meta-regressions were conducted to examine the association between CRF and cardiac output and arteriovenous oxygen difference. RESULTS A total of 44 studies were included, comprising 27 prospective trials (61%; n = 1,234 cancer survivors, median age 52.4 years) and 17 cross-sectional studies (39%; n = 1,372 cancer survivors, median age 54.0 years; n = 1,923 noncancer control subjects, median age 56.0 years). Systemic anticancer treatment was associated with a significant decrease in Vo(2peak) (weighted mean difference -2.13 mL<middle dot>kg(-1)<middle dot>min(-1); 95% CI: -2.76 to -1.50 mL<middle dot>kg(-1)<middle dot>min(-1)). No significant differences were observed between patient subgroups (esophagogastric, breast, and colon or rectal cancers). At a median follow-up of 2 years (range: 6 weeks to 12 years) post-therapy, cancer survivors had a significantly lower Vo(2peak) (weighted mean difference -6.39 mL<middle dot>kg(-1)<middle dot>min(-1); 95% CI: -7.60 to -5.18 mL<middle dot>kg(-1)<middle dot>min(-1)) compared with noncancer control subjects. Reduced arteriovenous oxygen difference was associated with lower Vo(2peak) (beta = 2.55; 95% CI: 2.05-3.06; P < 0.001). CONCLUSIONS Systemic anticancer treatment leads to substantial and sustained impairments in CRF.