Fecal volatile organic compounds for colorectal cancer detection: A systematic review and meta-analysis

Background: Fecal volatile organic compound (VOC) analysis has emerged as a promising non-invasive tool for detecting colorectal cancer (CRC). Despite its reported high diagnostic accuracy, clinical adoption is hindered due to issues like methodological variability, lack of standardization, and limited validation. This systematic review and meta-analysis aim to address these challenges by evaluating the diagnostic performance of fecal VOC analysis and exploring its future potential. A comprehensive search of studies assessing fecal VOC analysis for CRC detection and monitoring was conducted. Data on sensitivity, specificity, analytical platforms, and methodological protocols were extracted and analyzed. Seven studies met the inclusion criteria, and pooled diagnostic accuracy metrics were calculated. Emerging applications and challenges were critically reviewed. Fecal VOC analysis showed a pooled sensitivity of 0.86 and specificity of 0.90 for CRC detection, supported by an area under the summary receiver operating characteristic (SROC) curve of 0.89. Individual studies reported area under the curve (AUC) values ranging from 0.84 to 0.96, with some achieving perfect sensitivity and specificity using machine learning algorithms. Preliminary evidence suggests the potential of VOC profiling for monitoring CRC, but small sample sizes, methodological inconsistencies, and lack of external validation limit generalizability. Notably, while sensitivity was consistent, considerable heterogeneity in specificity was observed across studies. Variations in sample collection, storage, and analytical platforms introduce biases, and data on CRC staging and early detection remain scarce. To maximize the potential of fecal VOC analysis for CRC detection, staging, and post-treatment monitoring, future research must focus on standardizing procedures, conducting multi-center validation studies, and integrating VOC analysis with other diagnostic techniques. These efforts are particularly important given the limited number of studies currently available, which restricts the strength of evidence and highlights the need for larger, rigorous investigations. Overcoming these limitations could transform fecal VOC analysis from a promising research method into a reliable clinical tool for CRC diagnosis.