European Group of Tumor Markers (EGTM) Guidelines for Use of Biomarkers in Gastrointestinal Cancer: 2016
Members of the Gastrointestinal Cancer Focus Groups: MJ Duffy, Dublin, (Focus Group Leader); C Haglund, Helsinki; VL Holubec, Pilsen; M Kalousová, Prague; R Klapdor, Hamburg; A Nicolini, Pisa; R Lamerz, Munich; O Topolcan, Pilsen; C Sturgeon, Edinburgh.
Colorectal Cancer (CRC)
- For screening for colorectal cancer, a quantitative faecal immunochemical test (FIT) with an adjustable cut-off concentration should be used.
- Preoperative CEA levels may be combined with clinical and histopathological criteria in determining prognosis in patients with newly diagnosed colorectal cancer (CRC), especially in patients with stage II disease. There is however, no data at present to show that selection of treatment for stage II CRC, based on CEA levels, enhances outcome.
- For patients with stage II or III CRC who may be candidates for further intervention (e.g., liver resection or systemic treatment), in the event of recurrent disease, CEA should be measured at baseline and then every 2 to 3 months for at least 3 years after diagnosis.
- CEA should be used in monitoring therapy in patients with advanced CRC receiving chemotherapy. Caution is necessary when interpreting serial CEA level during the early weeks, following the initiation of specific cytotoxic therapies, as spurious or transient rises may occur. These transient increases which are also known as flares occur in 10-15% of patients with advanced CRC receiving chemotherapy. Compared to patients with consistently increasing CEA levels, these transient increases are associated with a favourable outcome.
- For patients with metastatic CRC who do not exhibit increased serum CEA levels, other markers such as CA 19-9 should be considered for monitoring therapy in advanced disease.
- Microsatellite instability (MSI) and/or detection of mismatch repair proteins by immunohistochemistry (eg, MLH1 and MSH2) may be used as a prescreen in patients with CRC to identify those that may have Lynch syndrome.
- MSI status and/or detection of mismatch repair proteins may also be used for determining prognosis, especially in patients with stage II colon cancer patients who are being considered for adjuvant 5-FU-based therapy.
- Patients with metastatic colorectal carcinoma who are candidates for anti-EGFR antibody therapy such as cetuximab or panitumumab should have their tumor tested for mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146). If any of these mutations are detected, then patients with metastatic colorectal carcinoma should not receive anti-EGFR antibody therapy.
- None of the available multigene gene signatures tests for CRC are sufficiently validated at this stage to be used for clinical purposes.
Gastric and Gastro-Oesophageal Junction (GOJ) Cancers
- In patients with advanced gastric or GOJ cancers, measurement of HER2 by immunohistochemistry is recommended for patients being considered for treatment with trastuzumab (Herceptin). Care should be taken that even focal positivity may be important for the decision to treat patients with Herceptin.
- CA 19-9 may be used as a diagnostic aid and for monitoring therapy in patients with pancreatic adenocarcinoma.
Gastrointestinal Stromal Tumors (GISTs)
- For patients with suspected GIST, determination of KIT protein by immunohistochemistry, should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with advanced GISTs.
- Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousová M, Holubec L, Sturgeon C. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer. 2014;134(11):2513-22. (There is free access to this article).
- Duffy MJ, van Dalen A, Haglund C, Hansson L, Klapdor R, Lamerz R, et al. Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. Eur J Cancer 2003;39:718-27.
- Duffy MJ. Personalized treatment for patients with colorectal cancer: role of biomarkers. Biomark Med 2015;9(4):337-47.
- Duffy MJ, van Dalen A, Haglund C, Hansson L, Holinski-Feder E, Klapdor R, et al. Tumor Markers in Colorectal Cancer: European Group on Tumor Markers (EGTM) Guidelines for Clinical Use. Eur J Cancer 2007;43:1348-1360.
- Duffy MJ, van Rossum LG, van Turenhout ST, Malminiemi O, Sturgeon C, Lamerz R, Nicolini A, Haglund C, Holubec L, Fraser CG, Halloran SP. Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper. Int J Cancer 2011;128:3-11.
- Duffy MJ, Sturgeon C, Lamerz R, Haglund C, Holubec VL, Klapdor R, Nicolini A, Topolcan O, Heinemann V. Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report. Ann Oncol 2010;21:441-7.