Objective Current cardiopulmonary exercise testing (CPET) guidelines for lung cancer surgery rely on expert consensus and scientific statements, lacking robust, graded evidence. This study aimed to provide an evidence-based evaluation of CPET variables for assessing perioperative morbidity and long-term mortality risks. Methods Electronic databases were searched through December 20, 2025, for cohort studies on CPET variables and lung cancer surgery. Quality was assessed using the Newcastle-Ottawa Scale. Heterogeneity was evaluated by the Q-test and I2 statistic, with fixed or random effects models. Publication bias was assessed via funnel plots and Egger’s test, with adjustment using the trim-and-fill method when necessary. Effect sizes were pooled, and evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Of 3080 studies, 47 studies involving 11,356 surgeries and 13 CPET variables were included. Meta-analysis and GRADE assessment showed lower peak oxygen uptake (peak <InlineEquation ID="IEq1"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>O₂) increased the risk of perioperative complications by 2.04–3.02 times (P < 0.001), using a cutoff point of 15 mL/kg/min or peak <InlineEquation ID="IEq2"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>O2 expressed as %pred. A higher minute ventilation to carbon dioxide production (<InlineEquation ID="IEq3"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>E/<InlineEquation ID="IEq4"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>CO₂) slope was associated with a 2.44-fold increased risk (95% CI [1.82–3.27], P < 0.001), with a cutoff point of 35 (high-level). Limited studies suggest peak <InlineEquation ID="IEq5"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>O₂ (L/min) and <InlineEquation ID="IEq6"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>E/<InlineEquation ID="IEq7"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>CO₂ slope relate to cancer-specific and all-cause mortality. Evidence for variables such as <InlineEquation ID="IEq8"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>O₂ at anaerobic threshold and peak ventilation remains low. Conclusion Among 13 CPET variables, only peak <InlineEquation ID="IEq9"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>O₂ (15 mL/kg/min or %pred values) and <InlineEquation ID="IEq10"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>E/<InlineEquation ID="IEq11"><EquationSource Format="TEX">$\dot{V}$</EquationSource><EquationSource Format="MATHML"><math><mover accent="true"><mi>V</mi><mo>˙</mo></mover></math></EquationSource></InlineEquation>CO₂ slope (35) are supported by high-certainty evidence for perioperative risk. Further studies are needed to establish CPET’s role in predicting cancer-specific mortality in lung cancer surgery. Systematic review registration PROSPERO CRD42023405083.

Grading the evidence for CPET variables in predicting perioperative morbidity and long-term mortality in lung cancer surgery: a systematic review and meta-analysis

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2026年7月10日

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Yaoshan Dun,
Jialin Yu,
Yang Gao,
Randal J. Thomas,
Ray W. Squires,
Thomas P. Olson,
Wenliang Zhang,
Shaoping Wu,
Yang Du,
Suixin Liu

摘要

Objective

Current cardiopulmonary exercise testing (CPET) guidelines for lung cancer surgery rely on expert consensus and scientific statements, lacking robust, graded evidence. This study aimed to provide an evidence-based evaluation of CPET variables for assessing perioperative morbidity and long-term mortality risks.

Methods

Electronic databases were searched through December 20, 2025, for cohort studies on CPET variables and lung cancer surgery. Quality was assessed using the Newcastle-Ottawa Scale. Heterogeneity was evaluated by the Q-test and I² statistic, with fixed or random effects models. Publication bias was assessed via funnel plots and Egger’s test, with adjustment using the trim-and-fill method when necessary. Effect sizes were pooled, and evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results

Of 3080 studies, 47 studies involving 11,356 surgeries and 13 CPET variables were included. Meta-analysis and GRADE assessment showed lower peak oxygen uptake (peak $\dot{V}$ $\dot{V}$ O₂) increased the risk of perioperative complications by 2.04–3.02 times (P < 0.001), using a cutoff point of 15 mL/kg/min or peak $\dot{V}$ $\dot{V}$ O₂ expressed as %pred. A higher minute ventilation to carbon dioxide production ($\dot{V}$ $\dot{V}$ E/$\dot{V}$ $\dot{V}$ CO₂) slope was associated with a 2.44-fold increased risk (95% CI [1.82–3.27], P < 0.001), with a cutoff point of 35 (high-level). Limited studies suggest peak $\dot{V}$ $\dot{V}$ O₂ (L/min) and $\dot{V}$ $\dot{V}$ E/$\dot{V}$ $\dot{V}$ CO₂ slope relate to cancer-specific and all-cause mortality. Evidence for variables such as $\dot{V}$ $\dot{V}$ O₂ at anaerobic threshold and peak ventilation remains low.

Conclusion

Among 13 CPET variables, only peak $\dot{V}$ $\dot{V}$ O₂ (15 mL/kg/min or %pred values) and $\dot{V}$ $\dot{V}$ E/$\dot{V}$ $\dot{V}$ CO₂ slope (35) are supported by high-certainty evidence for perioperative risk. Further studies are needed to establish CPET’s role in predicting cancer-specific mortality in lung cancer surgery.

Systematic review registration

PROSPERO CRD42023405083.