Giới thiệu

Physical fitness—particularly muscle strength and cardiorespiratory fitness (CRF)—plays a critical role in cancer survivorship. Emerging evidence suggests that these factors may significantly influence mortality risk in patients already diagnosed with cancer, yet most research has focused on healthy populations before cancer development. Simple, clinically feasible assessments like handgrip strength (HGS) and 6-minute walk tests (6MWT) show strong prognostic value, while advanced measures like cardiopulmonary exercise testing (CPET) provide deeper insights. Recent studies indicate that higher muscle strength may reduce all-cause mortality by up to 39% (Ezzatvar, 2021) and superior CRF may lower risk by 48% (Ezzatvar, 2021) but gaps remain—especially regarding cancer-specific mortality, tumor types, and disease stages.

This systematic review and meta-analysis aims to clarify these associations, helping physical therapists optimize exercise interventions for cancer patients at varying stages of progression by clarifying the relationship between physical fitness and cancer survival.

Phương pháp

Eligibility criteria

Studies were selected based on their examination of physical fitness and cancer survival outcomes in adult patients. The researchers performed a systematic search across major health sciences databases to identify prospective observational cohort studies investigating the relationship between muscle strength, cardiorespiratory fitness (CRF), and mortality in adult cancer patients (≥18 years). Only studies reporting all-cause or cancer-specific mortality were included, while those presenting odds ratios (ORs), non-English publications, or insufficient data were excluded.

Physical fitness was assessed using two analytical approaches:

1. Cut-off method (e.g., comparing high vs. low muscle strength/CRF groups).
2. Unit-increment method (e.g., evaluating mortality risk per 1-MET increase in CRF).

The study aimed to determine how baseline fitness levels and incremental improvements influence survival outcomes in cancer patients.

Data extraction and study quality assessment

Independent reviewers performed the data extraction. The team systematically collected: study characteristics (sample size, design, follow-up duration); participant demographics (age, BMI); clinical parameters (cancer type, stage, treatment regimen); and fitness measures (muscle strength and/or CRF assessment methods with cut-off values). For outcomes, Hazard Ratios (HRs) with 95% confidence intervals or standard errors were extracted for both all-cause and cancer-specific mortality from available univariable and multivariable analyses. The quality of the studies was then evaluated using the Newcastle– Ottawa Quality Assessment Scale for cohort studies. Three domains are assessed by this scale: Selection of the cohort group, comparability of cohorts and ascertainment of outcome of interest.

Statistical analysis

This study used meta-analysis to examine how muscle strength and cardiorespiratory fitness (CRF) affect all-cause and cancer-specific mortality. Researchers pooled hazard ratios (HRs) from previous studies using a random-effects model. They compared high vs. low strength/CRF groups based on predefined cutoffs and analyzed changes per unit increase (e.g., per 1-kg or 1-MET improvement). Statistical significance was set at *p* ≤ 0.05, and heterogeneity was assessed using I² and Cochran’s Q test. Sensitivity and publication bias analyses were performed. Subgroups included cancer stage and type.

Kết quả

Participants and interventions characteristics

The systematic review process identified 2702 studies investigating physical fitness and cancer survival, with 42 ultimately meeting inclusion criteria for meta-analysis. These studies collectively enrolled 46,694 adult cancer patients with a median age of 64 years and median BMI of 24.8 kg/m². The included studies represented various cancer types, including lung (9 studies), gastric (2), pancreatic (1), breast (1), glioma (1), and colon/bladder cancers (1 each), with 26 studies examining multiple cancer types.

Muscle strength measurments

All studies assessed muscle strength using Hand Grip strength dynamometry (HGS). Nineteen studies employed cutoff values to categorize patients into high versus low strength groups, with thresholds ranging from <13 kg to <25.1 kg for women and <19.87kg to <40.2 kg for men. Some studies used alternative classification methods including frailty indices or age-adjusted percentiles. Studies that analyzed strength as a continuous variable (changes per unit increment), examined mortality risk per 1 kg increment.

CRF measurments

Cardiorespiratory fitness was assessed through cardiopulmonary exercise testing (CPET) (14 studies) and 6-minute walk tests (4 studies). Low CRF was defined using multiple criteria including VO₂peak <13-16 mL/kg/min, minute ventilation (VE) to carbon dioxide output (VCO₂) ratio VE/VCO₂ ≥31, or 6MWT distance <358.5m to <400 m. Seven studies examined CRF as a continuous variable per unit increment in VO₂peak, METs, or walking distance.

Muscle strength: all-cause mortality.

Cut offs values

In multivariable analysis of 22 studies, high muscle strength was associated with a 31% lower mortality risk. Heterogeneity was moderate (I2 = 67%). The protective association was more pronounced in advanced cancers (23-46% risk reduction) compared to early-stage disease (non-significant). Univariable models showed similar but stronger effects with a 50% lower mortality risk for studies including more than 75% of participant with advanced stage cancer. The consistent mortality reductions demonstrate the prognostic value of physical fitness and cancer survival associations, with particularly robust linkages in advanced-stage disease. Patients with digestive cancer who had high muscle strength experienced a 41% lower risk of mortality compared to those with lower strength levels. Similarly, among patients with lung cancer, higher muscle strength was associated with a 19% reduction in all-cause mortality. When examining univariable analyses for these cancer types, the reduction in mortality risk was 38% for digestive cancer and 26% for lung cancer. Notably, the heterogeneity across studies for these cancer types was null (I² = 0%), indicating consistent findings.

Incremental values

Each 1 kg strength increase was associated with an 11% mortality reduction in multivariable models despite substantial heterogeneity (I2=94%). Similar findings were found in univariable analysis (6% reduction). The benefits were most evident in moderately advanced cancers (20% reduction per unit increment). An insufficient number of studies examined changes in mortality per unit increment when stratified by cancer type.

 Cardiorespiratory fitness: all causes mortality.

Cut offs analyses

High CRF showed a 46% lower mortality risk in multivariable analysis compared to those with lower CRF levels. However, heterogeneity was substantial I2=90%. Univariable models showed attenuated but significant effects (36% reduction). Multivariable analyses reported that lung cancer patients demonstrated particularly strong benefits (31% reduction). Univariable analyses showed a similar but slightly stronger effect, with a 35% reduction in mortality risk. For digestive and hematologic cancers, only univariable models were available, and they did not report a significant association between cardiorespiratory fitness and mortality. In early-stage cancers, high CRF showed non-significant mortality reduction in adjusted models, with moderate heterogeneity suggesting population-dependent effects.

Incremental values

Per-unit CRF increases showed non-significant mortality reductions (11-12%) in both multivariable and univariable models, with substantial heterogeneity observed (I²>95%). Similar results emerged from univariable model. An insufficient number of studies examined changes in mortality for cardiorespiratory fitness per unit increment when stratified by cancer type and stage.

Cardiorespiratory fitness cancer specific mortality.

Cut offs analyses

High CRF showed non-significant mortality reductions (66% in adjusted, 49% in unadjusted models) with extreme heterogeneity (I²>94%). Limited data were available to examine CRF-mortality relationships across specific cancer types and stages.

Incremental values

Two studies found each CRF unit increment was associated with an 18% lower cancer-specific mortality risk in adjusted models. However, the heterogeneity was substantial (I2=90%). An insufficient number of studies were available to examine cancer-specific mortality risk per unit increment in CRF when stratified by cancer stage and type.

Câu hỏi và suy nghĩ

This systematic review examined both multivariable and univariable analyses from prospective observational cohort studies. While these studies reveal important associations, it’s crucial to remember they can only identify correlations – not establish causation between physical fitness and cancer survival. The observational design means we must interpret results cautiously, particularly since univariable analyses tend to overestimate the effects of strength and cardiorespiratory fitness on mortality risk by failing to account for potential confounding variables.

Several limitations emerge from the current evidence. High heterogeneity between studies (with I² values often exceeding 50%) indicates significant variability in patient populations, assessment methods, and outcome measures. This heterogeneity, combined with incomplete reporting of adjusted covariates in some multivariable

analyses, makes it challenging to isolate the specific effects of physical fitness. Furthermore, our incomplete understanding of all factors influencing cancer mortality complicates efforts to determine the precise role of strength and cardiorespiratory conditioning.

Practical implementation faces real-world barriers. Cancer patients often experience treatment-related fatigue and other side effects that create significant challenges for maintaining or improving physical fitness. These clinical realities must be considered when applying these findings to patient care, as the study populations may not fully represent the broader cancer patient experience.

Nói chuyện với tôi một cách ngớ ngẩn

To analyze how muscle strength and cardiorespiratory fitness (CRF) relate to mortality, the study first gathered hazard ratios (HRs) from existing research. These HRs—along with their 95% confidence intervals (CIs)—were mathematically adjusted to ensure fair comparisons. A random-effects model was then used to combine results, which explicitly accounts for differences between studies by assuming their true effects vary naturally (e.g., due to varying patient populations or measurement methods). This is more conservative than a fixed-effect model, as it widens confidence intervals to reflect this uncertainty. This model assigned greater weight to more precise studies through inverse variance weighting, a method that prioritizes estimates with smaller standard errors.

For studies comparing “high versus low” fitness categories, predefined cutoffs (like >19.1 kg for muscle strength) split participants into groups. When studies organized data into tertiles or quartiles, only the top and bottom groups were analyzed to maximize contrast. Another approach focused on incremental changes, such as how each 1-MET improvement in CRF affected mortality risk.

The team assessed statistical significance using a *p*-value threshold of 0.05. To gauge whether study results conflicted, they calculated heterogeneity via the I² statistic (values over 50% indicated substantial differences) and Cochran’s Q test. For example, an I² of 90% (as seen in some analyses here) suggests >90% of observed differences between studies reflect real inconsistencies rather than random error. When heterogeneity is high, the pooled estimates become less reliable, subgroup analyses might explain in part these differences as seen when early- and advanced-stage cancers showed divergent results.

Potential outliers were flagged using sensitivity analysis, where each study was temporarily removed to check its impact (leave-one-out method). Publication bias—the risk of missing negative studies—was evaluated with funnel plots and Egger’s test, which detect imbalances in small-study effects.

Subgroup analyses explored whether results varied by cancer stage (early vs. advanced) or type (e.g., lung cancer alone vs. grouped digestive cancers). All calculations were performed using Review Manager (RevMan) and R’s metafor package, standard tools for meta-analyses.

Những thông điệp mang về nhà

Current evidence strongly suggests that improving muscle strength and cardiorespiratory fitness (CRF) in cancer patients may significantly reduce risks of both cancer-specific and all-cause mortality, though the exact protective effects require further quantification due to study limitations like heterogeneity and small sample sizes. Key clinical patterns emerge:

• Strength Matters: Higher muscle strength is consistently linked to 31-46% lower mortality risk in advanced cancers, with notable benefits for digestive and lung cancers.
• Cardiorespiratory fitness: Each 1-MET increase in CRF may lower mortality risk by 11-18%, with even greater benefits in lung cancer patients (31% reduction).
• Stage-Specific Effects: These protective associations are strongest in advanced-stage cancers, highlighting the critical role of rehab even during late-phase care.

Practical Implications:

• Prioritize progressive resistance training to build strength (targeting major muscle groups).
• Incorporate aerobic conditioning (e.g., walking, cycling) to improve CRF, even modestly.
• Monitor patient progress using functional measures (e.g., grip strength, 6MWT) alongside symptoms.
• Identify and address barriers to physical activity to foster patient’s adherence.

Although the link between physical fitness and cancer survival is well-documented, other clinical factors significantly influence outcomes. Our review offers comprehensive analysis of these interacting risk factors.

Thẩm quyền giải quyết

Bettariga F, Galvao DA, Taaffe DR, et alAssociation of muscle strength and cardiorespiratory fitness with all-cause and cancer-specific mortality in patients diagnosed with cancer: a systematic review with meta-analysisBritish Journal of Sports Medicine 2025;59:722-732.