This is the current release of the guideline.

This guideline updates a previous version: 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001 Mar 15;19(6):1865-1878.

Gastrointestinal cancer, including colorectal cancer and pancreatic cancer

Evaluation
Management
Risk Assessment
Screening
Technology Assessment
Treatment

Colon and Rectal Surgery
Family Practice
Gastroenterology
Internal Medicine
Oncology
Radiation Oncology
Surgery

Physicians

To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of gastrointestinal cancers

Patients with colorectal cancer or pancreatic cancer

1. Preoperative carcinoembryonic antigen (CEA) testing for staging and surgical treatment planning
2. Postoperative CEA testing to detect possible metastatic disease
3. CEA testing to monitor metastatic colorectal cancer during systemic therapy
4. CA 19-9 testing for monitoring response to therapy

Note: The following interventions were considered but not recommended.

• CEA as a screening test for colorectal cancer
• CEA testing to determine whether to treat patients with colorectal cancer with adjuvant therapy
• Use of CA 19-9 for screening, diagnosis, staging, surveillance, or monitoring treatment of patients with colorectal cancer
• Use of flow-cytometrically derived DNA ploidy (DNA index) or DNA flow cytometric proliferation analysis (%S phase) to determine prognosis of early stage colorectal cancer
• Use of p53 expression or mutation for screening, diagnosis, staging, surveillance, or monitoring treatment of patients with colorectal cancer
• Use of the ras oncogene for screening, diagnosis, staging, surveillance, or monitoring treatment of patients with colorectal cancer
• Use of thymidine synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) tests for screening, prognosis, predicting response to therapy, or monitoring response to therapy of patients with colorectal cancer
• Microsatellite instability (MSI) ascertained by polymerase chain reaction (PCR) to determine the prognosis of operable colorectal cancer or to predict the effectiveness of fluorouracil (FU) adjuvant chemotherapy
• Assaying for loss of heterozygosity (LOH) on the long arm of chromosome 18 (18q) or deleted in colon cancer (DCC) protein determination by immunohistochemistry to determine the prognosis of operable colorectal cancer, or to predict response to therapy
• Use of CA 19-9 as a screening test for pancreatic cancer
• Use of CA 19-9 testing alone for determining operability or the results of operability in pancreatic cancer and for providing definitive evidence of disease recurrence

• Overall survival
• Disease-free survival
• Quality of life
• Toxicity
• Cost-effectiveness

Hand-searches of Published Literature (Primary Sources)
Searches of Electronic Databases

For the 2006 update, methodology was used that was similar to that applied in the original American Society of Clinical Oncology (ASCO) practice guidelines for use of tumor markers. Pertinent information published from 1999 through November 2005 was reviewed for markers that were included in the last update of the guideline; information from 1966 to November 2005 was reviewed for the new markers. The Medline database (National Library of Medicine, Bethesda, MD ) was searched to identify relevant information from the published literature for this update. A series of searches was conducted using the medical subject headings or text words for each of the markers with the corresponding disease site (colon, rectal, or pancreatic cancer). Search results were limited to human studies and English-language articles; editorials, letters, and commentaries were excluded from consideration. The Cochrane Library was searched for available systematic reviews and meta-analyses using the phrases, "tumor markers" and "biomarkers." Directed searches based on the bibliographies of primary articles were also performed. Finally, Update Committee members contributed articles from their personal collections. Update Committee members reviewed the resulting abstracts and titles that corresponded to their assigned section. Inclusion criteria were broad. Update Committee members focused attention on systematic reviews and meta-analyses, and on studies that considered markers in relation to ASCO clinical outcomes for guideline and technology assessment (overall survival, disease-free survival, quality of life, toxicity, and cost-effectiveness).

Not stated

Expert Consensus

Not applicable

Review of Published Meta-Analyses
Systematic Review

Not stated

Expert Consensus

The American Society of Clinical Oncology (ASCO) first published evidence-based clinical practice guidelines for the use of tumor markers in colorectal cancer in 1996. ASCO guidelines are updated at intervals by an update committee of the original expert panel. The last update of the tumor markers guideline was published in 2000. For the 2006 update, the Panel expanded the scope of the guideline to include a broader range of markers in colorectal cancer and, new to this guideline, pancreatic cancer markers.

The Update Committee had two face-to-face meetings to consider the evidence for each of the 2000 recommendations.

Not applicable

Published studies or reviews of cost-effectiveness were considered in the preparation of this guideline:

• Carcinoembryonic antigen (CEA) is considered a valuable component of postoperative follow-up, is the most frequent indicator of recurrence in asymptomatic patients, is more cost-effective than radiology for the detection of potential curable recurrence, and is the most sensitive detector for liver metastases.
• Economic analyses suggest that intensive follow-up that incorporates CEA testing is cost-effective compared with conventional follow-up.

Internal Peer Review

The guideline was circulated in draft form to the Update Committee, per the American Society of Clinical Oncology (ASCO) guideline policy. ASCO's Health Services Committee and the ASCO Board of Directors also reviewed the final document.

Carcinoembryonic Antigen as a Marker for Colorectal Cancer

2006 recommendation for carcinoembryonic antigen as a screening test. Carcinoembryonic antigen (CEA) is not recommended for use as a screening test for colorectal cancer.

2006 recommendation for preoperative carcinoembryonic antigen (CEA) testing. CEA may be ordered preoperatively in patients with colorectal carcinoma if it would assist in staging and surgical treatment planning. Although elevated preoperative CEA (>5 mg/mL) may correlate with poorer prognosis, data are insufficient to support the use of CEA to determine whether to treat a patient with adjuvant therapy.

2006 recommendation for postoperative CEA testing. Postoperative serum CEA testing should be performed every 3 months in patients with stage II or III disease for at least 3 years after diagnosis if the patient is a candidate for surgery or systemic therapy. An elevated CEA, if confirmed by retesting, warrants further evaluation for metastatic disease, but does not justify the institution of adjuvant therapy or systemic therapy for presumed metastatic disease (Ueno et. al, 2000). CEA elevations within a week or two following chemotherapy should be interpreted with caution (Sorbye & Dahl, 2003).

2006 recommendation for CEA testing to monitor metastatic colorectal cancer. CEA is the marker of choice for monitoring metastatic colorectal cancer during systemic therapy. CEA should be measured at the start of treatment for metastatic disease and every 1 to 3 months during active treatment. Persistently rising values above baseline should prompt restaging, but suggest progressive disease even in the absence of corroborating radiographs. Caution should be used when interpreting a rising CEA level during the first 4 to 6 weeks of a new therapy, since spurious early rises may occur especially after oxaliplatin use (Sorbye & Dahl, 2003; Sorbye & Dahl, 2004).

CA 19-9 As a Marker for Colon Cancer

2006 recommendation for use of CA 19-9 in colon cancer. Present data are insufficient to recommend CA 19-9 for screening, diagnosis, staging, surveillance, or monitoring treatment of patients with colorectal cancer.

DNA Ploidy or Flow Cytometric Proliferation Analysis As a Marker for Colon Cancer

2006 recommendation for DNA ploidy or DNA flow cytometric proliferation analysis to determine prognosis. Neither flow-cytometrically derived DNA ploidy (DNA index) nor DNA flow cytometric proliferation analysis (%S phase) should be used to determine prognosis of early-stage colorectal cancer.

p53 As a Marker for Colorectal Cancer

2006 recommendations for p53 testing. Present data are insufficient to recommend the use of p53 expression or mutation for screening, diagnosis, staging, surveillance, or monitoring treatment of patients with colorectal cancer.

ras As a Marker for Colorectal Cancer

2006 recommendation for ras testing. Present data are insufficient to recommend the use of the ras oncogene for screening, diagnosis, staging, surveillance, or monitoring treatment of patients with colorectal cancer.

Thymidine Synthase, Dihydropyrimidine Dehydrogenase, and Thymidine Phosphorylase As Markers in Colorectal Cancer

Note: These topics are new to the guideline.

2006 recommendation for thymidine synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase as screening tests. Thymidine synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) are tissue markers that have been used to predict response to treatment of established carcinomas and thus are not useful for screening.

2006 recommendation for use of TS, DPD, or TP for prognosis. None of the three markers—TS, DPD, or TP—are recommended for use to determine the prognosis of colorectal carcinoma.

2006 recommendation for use of TS, DPD, or TP in predicting response to therapy. There is insufficient evidence to recommend use of TS, DPD, or TP as predictors of response to therapy.

2006 recommendation for use of TS, DPD, or TP in monitoring response to therapy. There is insufficient evidence to recommend use of TS, DPD, or TP for monitoring response to therapy.

Microsatellite Instability/hMSH2 or hMLH1 As Markers in Colorectal Cancer

Note: This topic is new to the guideline.

2006 recommendation for use of microsatellite instability to determine prognosis. Microsatellite instability (MSI) ascertained by polymerase chain reaction (PCR) is not recommended at this time to determine the prognosis of operable colorectal cancer nor to predict the effectiveness of FU adjuvant chemotherapy.

1 8q-LOH/DCC As Markers for Colorectal Cancer

Note: This topic is new to the guideline.

2006 recommendation for use of 18q-LOH/DCC to determine prognosis or to predict response to therapy. Assaying for loss of heterozygosity (LOH) on the long arm of chromosome 18 (18q) or deleted in colon cancer (DCC) protein determination by IHC should not be used to determine the prognosis of operable colorectal cancer, nor to predict response to therapy.

CA 19-9 as a Marker for Pancreatic Cancer

Note: This topic is new to the guideline.

2006 recommendation for use of CA 19-9 as a screening test. CA 19-9 is not recommended for use as a screening test for pancreatic cancer.

2006 recommendation for use of CA 19-9 to determine operability. The use of CA19- 9 testing alone is not recommended for use in determining operability or the results of operability in pancreatic cancer.

2006 recommendation for use of CA 19-9 to provide evidence of recurrence. CA 19-9 determinations by themselves cannot provide definitive evidence of disease recurrence without seeking confirmation with imaging studies for clinical findings and/or biopsy.

2006 recommendation for use of CA19-9 for monitoring response to therapy. Present data are insufficient to recommend the routine use of serum CA 19-9 rules alone for monitoring response to treatment. However, CA19-9 can be measured at the start of treatment for locally advanced metastatic disease and every 1 to 3 months during active treatment. If there is an elevation in serial CA19-9 determinations, this may be an indication of progressive disease, and confirmation with other studies should be sought.

None provided

The evidence supporting each recommendation is presented in the original guideline document under "literature update and discussion" following each recommendation. The Update Committee's literature review focused attention on available systematic reviews and meta-analyses of published tumor marker studies. By and large, however, the literature is characterized by studies that included small patient numbers, studies that were retrospective, and studies that commonly performed multiple analyses until one revealed a statistically significant result (P<.05). In the scale for grading the clinical utility of tumor markers used by the Update Committee, these studies are designated as Level of Evidence III.

Appropriate use of tumor markers for prevention, screening, treatment, and surveillance of gastrointestinal tumors

Not stated

• By and large the literature is characterized by studies that included small patient numbers, studies that were retrospective, and studies that commonly performed multiple analyses until one revealed a statistically significant result (P<.05). In the scale for grading the clinical utility of tumor markers used by the Update Committee, these studies are designated as Level of Evidence III. The Level of Evidence in this grading scale defines the quality of the data on a given marker. The Update Committee underscores that the preferred way to assess tumor markers is within Level of Evidence II studies (prospective therapeutic trials in which marker utility is a secondary study objective), or, ideally, within Level of Evidence I studies (single, high-powered, prospective, randomized controlled trials specifically designed to test the marker or a meta-analyses of well-designed studies).
• It is important to emphasize that guidelines and technology assessments cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments reasonably directed at obtaining the same result. Accordingly, the American Society of Clinical Oncology (ASCO) considers adherence to this guideline assessment to be voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. In addition, this guideline describes the use of procedures and therapies in clinical practice; it cannot be assumed to apply to the use of these interventions performed in the context of clinical trials, given that clinical studies are designed to evaluate or validate innovative approaches in a disease for which improved staging and treatment is needed.

An implementation strategy was not provided.

Getting Better
Living with Illness
Staying Healthy

Effectiveness
Patient-centeredness

Not applicable: The guideline was not adapted from another source.

1996 (revised 2006 Nov 20)

American Society of Clinical Oncology - Medical Specialty Society

American Society of Clinical Oncology

American Society of Clinical Oncology (ASCO) Expert Panel

Panel Members: Robert C. Bast Jr, MD (Co-Chair) M.D. Anderson Cancer Center; Daniel F. Hayes, MD (Co-Chair) University of Michigan Medical Center; Dean F. Bajorin, MD,  Memorial Sloan-Kettering Cancer Center; Jonathan S. Berek, MD, UCLA School of Medicine; Ross S. Berkowitz, MD, Brigham & Women's Hospital; Roy Beveridge, MD, Fairfax Northern VA Hem-Onc; Herbert Fritsche Jr, PhD, M.D. Anderson Cancer Center; Timothy Gilligan, MD, Dana-Farber Cancer Institute; Stanley Hamilton, MD, M.D. Anderson Cancer Center; Jules Harris, MD, Rush University Medical Center; Lyndsay Harris, MD, Dana-Farber Cancer Institute; John M. Jessup, MD, Georgetown University Medical Center; Philip W. Kantoff, MD, Dana-Farber Cancer Institute; Nancy E. Kemeny, MD, Memorial Sloan-Kettering Cancer Center; Ann Kolker Ovarian Cancer National Alliance, consultant and founding director; Susan Leigh, BSN, RN, National Coalition for Cancer Survivorship, patient representative; Gershon Y. Locker, MD, Evanston Northwestern Healthcare; Juanita Lyle, George Washington University, patient representative; John S. Macdonald, MD, St Vincent's Comprehensive Cancer Center; Pam McAllister, PhD, Science advocate with the Colorectal Cancer Coalition, patient representative; Robert G. Mennel, MD, Texas Oncology PA; Larry Norton, MD, Memorial Sloan-Kettering Cancer Center; Peter Ravdin, MD, The University of Texas Health Science Center; Sheila Taube, PhD National Cancer Institute

Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

This is the current release of the guideline.

This guideline updates a previous version: 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001 Mar 15;19(6):1865-1878.

This NGC summary was completed by ECRI on November 21, 2006. The information was verified by the guideline developer on December 6, 2006.

This summary is based on the original guideline, which is subject to the American Society of Clinical Oncology's copyright restrictions.