The performance of the mSEPT9 assay is influenced by algorithm, cancer stage and age, but not sex and cancer location

Purpose This study aims to examine the influence of algorithm and subject-related factors, including cancer stage, age, sex, and cancer location, on the performance of the SEPT9 gene methylation test, an assay approved by the US FDA for colorectal cancer (CRC) screening. Methods A total of 1225 subjects were recruited in this opportunistic screening study, including 388 CRC patients, 139 subjects with adenoma, 108 subjects with hyperplastic polyps, and 590 subjects with no evidence of disease (NED). Epi proColon 2.0 CE assay was used to examine the blood level of SEPT9 gene methylation. Results It was found that tests using 1/3 algorithm exhibited higher detection rate than those using the 2/3 algorithm for CRC, adenoma, hyperplastic polyps, while the false positive rate in subjects with NED was also higher with 1/3 algorithm. The positive detection rate (PDR) of the assay for stage 0 and I CRC were lower than later stages (Stage II, III and IV). Interestingly, the normal subjects above 60 years old exhibited significantly higher PDR than subjects from younger groups, while no significant change in PDR was observed among age groups in CRC patients. Furthermore, no difference in the PDR for CRC was found between male and female, and the PDR for CRC at various colorectal locations were essentially identical. Conclusions Algorithm, cancer stage and age are factors affecting the detection rate of the SEPT9 assay, while sex and cancer location appeared to have no influence on its performance.