FDG-PET/CT Parameters for distinguishing high and low microsatellite instability in colorectal cancer: A systematic review and Meta-analysis.

Microsatellite instability (MSI) is a key prognostic biomarker in colorectal cancer (CRC), guiding immunotherapy planning. MSI testing requires invasive and costly tissue sampling. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) offers noninvasive metabolic profiling and may capture MSI-associated heterogeneity.

This study evaluated the utility of PET-derived parameters for distinguishing high MSI (MSI-H) from low MSI (MSI-L) CRC. Following PRISMA guidelines, PubMed, Embase, Scopus, and Web of Science were searched through October 2025. Included studies reported mean and standard deviation for either of SUVmax, SUVmean, MTV, TLG for MSI groups. Random-effects models generated pooled standardized mean differences (SMDs).

Heterogeneity was evaluated using I², with subgroup analysis and meta-regression exploring its sources. Publication bias was assessed using Begg's test and trim-and-fill. Ten studies (1,579 patients; 246 MSI-H) were included. SUVmax (SMD: 0.22; 95% CI: -0.02 to 0.46) and SUVmean (SMD: 0.39; 95% CI: -0.01 to 0.80) showed no significant differences.

Volumetric measures demonstrated significant discriminatory power: MTV (SMD: 0.67; 95% CI: 0.41 to 0.93; I²=0%) and TLG (SMD: 0.37; 95% CI: 0.13 to 0.60; I²=0%). MTV showed the highest diagnostic performance (AUC up to 0.805). Studies using polymerase chain reaction showed larger SUVmax SMD than those using immunohistochemistry (p = 0.03). A marginal inverse association was found between SUVmax SMD and proportion of high-grade tumor (p = 0.09).

Publication bias was detected for SUVmax (p = 0.02). Volumetric PET parameters, particularly MTV, showed relatively higher performance than intensity-based metrics for distinguishing MSI status in CRC; however, given the limited evidence and moderate diagnostic accuracy, they should be considered adjunctive imaging biomarkers and not a replacement for tissue-based assessment.