Predictive Accuracy of Chemotherapy Toxicity Tools in Older Adults with Cancer: A Systematic Review and Diagnostic Test Accuracy Meta-Analysis.

BACKGROUND

Older adults with cancer are at increased risk of severe treatment-related toxicity. CARG, CRASH, and CARG-BC were developed as toxicity-risk prediction models, whereas G8 was developed as a geriatric screening instrument but has also been evaluated as a predictor of treatment-related toxicity. This study aimed to assess, separately for each instrument, the accuracy with which these tools identify older adults who develop severe chemotherapy-related toxicity.

METHODS

A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. Seven databases were searched through May 2026 for observational studies evaluating the predictive accuracy of the CARG, CRASH, CARG-BC and G8 tools in patients aged ≥65 years initiating chemotherapy. Pooled sensitivity and specificity with 95% confidence intervals (CIs) were calculated, and ROC curves were constructed. Risk of bias was assessed using QUADAS-2 and certainty of evidence was evaluated using GRADE.

RESULTS

Twenty-one studies were included, with an overall toxicity prevalence of 52.6%. CARG demonstrated a pooled sensitivity of 79.7% and specificity of 38.3% (AUC = 0.632). CRASH showed sensitivity of 86.9% and specificity of 68.2% (AUC = 0.866), but estimates were based on only four studies. CRASH hematological toxicity showed sensitivity of 75.9% and specificity of 53.1% (AUC = 0.694), with substantial heterogeneity. G8 yielded sensitivity of 69.5% and specificity of 41.5% (AUC = 0.666). CARG-BC showed sensitivity of 83.3% and specificity of 54.4% (AUC = 0.763), based on two breast cancer studies. Certainty of evidence ranged from low to very low.

CONCLUSIONS

The instruments have distinct purposes and were not pooled against one another. CARG and G8 may be useful for initial risk screening, whereas CRASH showed a more balanced profile but remains supported by limited evidence. None should be used as a stand-alone basis to withhold or modify treatment.