Comparative Diagnostic Accuracy of Fecal Protein Biomarkers for Colorectal Advanced Neoplasms: A Systematic Review and Meta-Analysis

Early diagnosis of colorectal advanced neoplasms (AN), including colorectal cancer (CRC) and advanced adenoma (AA), has positive effect on survival rate. As the first attempt, the aim of this meta-analysis was to compare the diagnostic accuracy of fecal protein biomarkers for detection of colorectal neoplasms with consideration of wide range covariates.Until Jun 10, 2021, a systematic literature search was performed on Web of Sciences, Scopus and PubMed. The diagnostic accuracies were calculated using the bivariate/hierarchical random effect model. Biomarkers were determined clinically applicable (CA) if they had area under the curves> 0.70, positive and negative likelihood ratio >2 and <0.5, respectively. A total of 47059 test results were extracted from 16 Immunochemical fecal occult blood test (iFOBT), 26 Pyruvate Kinase-M2 (PK-M2) and 23 Fecal Calprotectin (FC) studies. Only iFOBT, PK-M2 and FC for CRC plus iFOBT and PK-M2 for AN were CA. iFOBT had significantly superior accuracy (P= 0.02 versus PK-M2 and P< 0.01 versus FC for CRC; P< 0.01 versus PK-M2 for AN). Regarding covariates, lateral flow method of PK-M2 measurement increased its accuracy for CRC detection compared to enzyme-linked immunosorbent assay (P< 0.01). Briefly, iFOBT is the most accurate fecal biomarker for diagnosis of CRC and AN.