Clean Colorectum at Diagnostic Colonoscopy: Subsequent Detection of Extracolonic Malignancies by Plasma Protein Biomarkers?

Abstract

Introduction:Most of the subjects undergoing diagnostic colonoscopy do not have neoplastic bowel lesions. Potentially, some of the symptoms may therefore be caused by extracolonic malignancy, and subjects with persisting symptoms may need subsequent examinations. Blood-based, cancer-associated biomarkers may aid in directing the examinations for other specific malignant diseases.Methods:EDTA plasma samples available from a previous prospective study of subjects undergoing diagnostic colonoscopy were used for analysis of 18 protein biomarkers. The study population of 3732 subjects included 400 patients with colorectal cancer (CRC) and 177 patients with extracolonic malignancies. Univariable analysis of the association of specific biomarkers and extracolonic cancers included those with 10 or more cases. Subsequently, reduced models of 4 or 6 biomarkers, respectively, were established by choosing those with the highest likelihood; age and sex were included as well.Results:Univariable analyses showed that CyFra21-1 had an area under curve (AUC) of 0.87 for lung cancers (n = 33), CA19-9 had an AUC of 0.85 for pancreatic cancer (n = 22), CA125 had an AUC of 0.95 for ovary cancer (n = 16), B2M had an AUC of 0.81 for non-Hodgkin lymphoma (n = 12), and total prostate-specific antigen had an AUC of 0.99 for prostate cancer (n = 10). The multivariable analysis of 4 or 6 biomarkers plus age and sex as explanatory variables showed AUCs of 0.82 to 0.85 both for extracolonic cancers and CRC. The 4 biomarkers included in the model for detection of extracolonic cancers were CA125, hsCRP, CA19-9, and CyFra21-1; the 2 additional for the 6 biomarkers model were CEA and Galectin-3. Similarly, the 4 biomarkers included in the model for detection of CRC were CEA, CyFra21-1, Ferritin, and HE4; the two additional for the 6 biomarkers model were hsCRP and Pepsinogen 2.Conclusions:Results of this study indicate that it may be possible to detect subjects that have an increased risk of extracolonic cancer following a colonoscopy without findings of neoplastic lesions. Combinations of various protein biomarkers may direct subsequent examination after colonoscopy with clean colorectum. The results, although preliminary, may form the basis for additional research directed both for primary examinations of subjects with symptoms of malignancy and subsequent examinations after colonoscopy.

The performance of FIT-based and other risk prediction models for colorectal neoplasia in symptomatic patients: a systematic review

“…All included studies were of an observational study design, with 21 cross-sectional studies, 19 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 17 retrospective studies, 18 , 30 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 15 prospective studies, 39 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 and eight case–control studies. 62 , 75 , 76 , 77 , 78 , 79 , 80 One study design was unclear, as it was an abstract only.…”

“…Settings were primary care (n = 21), 30 , 31 , 35 , 47 , 50 , 51 , 52 , 53 , 54 , 56 , 59 , 62 , 64 , 66 , 68 , 71 , 73 , 77 , 78 , 80 primary and secondary care (n = 12), 18 , 19 , 30 , 33 , 34 , 49 , 60 , 63 , 65 , 67 , 72 secondary care (n = 24), 29 , 32 , 36 , 37 , 38 , 39 , 41 , 42 , 43 , 44 , 46 , 48 , 55 , 57 , 58 , 61 , 62 , 69 , 70 , 74 , 75 , 76 , 79 , 82 secondary and tertiary care (n = 3), 27 , 28 , 40 and tertiary care (n = 1). 45 One study was unclear regarding the setting.…”

“…One study examined patients from two different countries: Scotland and Spain. 18 A further 24 studies assessed patients from the UK, 30 , 31 , 38 , 41 , 43 , 44 , 45 , 46 , 47 , 51 , 56 , 57 , 59 , 60 , 61 , 62 , 66 , 70 , 71 , 77 , 80 , 81 eight from Denmark, 35 , 39 , 48 , 69 , 74 , 76 , 79 , 82 seven from Spain, 19 , 30 , 34 , 40 , 49 , 63 , 65 five from the Netherlands, 50 , 52 , 53 , 54 , 64 five from Sweden, 67 , 68 , 78 , 83 , 84 four from Australia, 27 , 28 , 37 , 72 two from China, 32 , 55 one from the USA, 73 one from Canada, 42 one from New Zealand, 58 one from Egypt, 75 one from Italy, 36 one from Malaysia 33 and one from Nigeria. 29 For further...…”

Serological cancer-associated protein biomarker levels at bowel endoscopy: Increased risk of subsequent primary malignancy

“…Age as a covariate should be included in the algorithms as greater age itself leads to an increased risk of subsequent malignancy [66]. Specific calculated malignancy risks may aid in targeting cancer search in individuals with unspecific signs of malignancy and refer these individuals to special cancer investigation departments and/or help specialists at such departments making the right diagnosis [67][68][69][70][71]. In Denmark 'Diagnostic Departments' were established in April 2012.…”

Increased serological, cancer-associated protein biomarker levels at diagnosis of large bowel adenoma: Risk of subsequent primary malignancy?

“…Such future combinations may lead to specific risk stratifications through algorithmic calculations based on the number and specificity of elevated biomarkers. Thus, a subject with elevated cancerassociated biomarkers may get different specific cancer risks calculated, and that may be of benefit to target the future cancer search [31,32].…”