Laboratory Medicine Practice Guidelines Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers Edited by Catharine M. Sturgeon and Eleftherios Diamandis NACB_LMPG_Ca1cover.indd 1 11/23/09 1:36:03 PM Tumor Markers.qxd 6/22/10 7:51 PM Page i The National Academy of Clinical Biochemistry Presents LABORATORY MEDICINE PRACTICE GUIDELINES USE OF TUMOR MARKERS IN TESTICULAR, PROSTATE, COLORECTAL, BREAST, AND OVARIAN CANCERS EDITED BY Catharine M. Sturgeon Eleftherios P. Diamandis Copyright © 2009 The American Association for Clinical Chemistry Tumor Markers.qxd 6/22/10 7:51 PM Page ii National Academy of Clinical Biochemistry Presents LABORATORY MEDICINE PRACTICE GUIDELINES USE OF TUMOR MARKERS IN TESTICULAR, PROSTATE, COLORECTAL, BREAST, AND OVARIAN CANCERS EDITED BY Catharine M. Sturgeon Eleftherios P. Diamandis Catharine M. Sturgeon Robert C. Bast, Jr Department of Clinical Biochemistry, Department of Experimental Therapeutics, University of Royal Infirmary of Edinburgh, Texas M. D. Anderson Cancer Center, Houston, TX Edinburgh, UK Barry Dowell Michael J. Duffy Abbott Laboratories, Abbott Park, IL Department of Pathology and Laboratory Medicine, St Vincent’s University Hospital and UCD School of Francisco J. Esteva Medicine and Medical Science, Conway Institute of Departments of Breast Medical Oncology, Molecular Biomolecular and Biomedical Research, University and Cellular Oncology, University of Texas M. D. College Dublin, Dublin, Ireland Anderson Cancer Center, Houston, TX Ulf-Håkan Stenman Caj Haglund Department of Clinical Chemistry, Helsinki University Department of Surgery, Helsinki University Central Central Hospital, Helsinki, Finland Hospital, Helsinki, Finland Hans Lilja Nadia Harbeck Departments of Clinical Laboratories, Urology, and Frauenklinik der Technischen Universität München, Medicine, Memorial Sloan-Kettering Cancer Center, Klinikum rechts der Isar, Munich, Germany New York, NY 10021 Daniel F. Hayes Nils Brünner Breast Oncology Program, University of Michigan Section of Biomedicine, Department of Veterinary Comprehensive Cancer Center, Ann Arbor, MI Pathobiology, Faculty of Life Sciences, University of Copenhagen, Denmark Mads Holten-Andersen Section of Biomedicine, Department of Veterinary Daniel W. Chan Pathobiology, Faculty of Life Sciences, University of Departments of Pathology and Oncology, Johns Hopkins Copenhagen, Denmark Medical Institutions, Baltimore, MD George G. Klee Richard Babaian Department of Laboratory Medicine and Department of Urology, The University of Texas M. D. Pathology, Mayo Clinic College of Medicine, Anderson Cancer Center, Houston, TX Rochester, MN Tumor Markers.qxd 6/22/10 7:51 PM Page iii Rolf Lamerz Paul Sibley Department of Medicine, Klinikum of the University Siemens Medical Solutions Diagnostics, Glyn Rhonwy, Munich, Grosshadern, Germany Llanberis, Gwynedd, UK Leendert H. Looijenga György Sölétormos Laboratory of Experimental Patho-Oncology, Erasmus Department of Clinical Biochemistry, Hillerød Hospital, MC-University Medical Center Rotterdam, and Daniel den Hillerød, Denmark Hoed Cancer Center, Rotterdam, The Netherlands Carsten Stephan Rafael Molina Department of Urology, Charité Hospital, Laboratory of Biochemistry, Hospital Clinico Provincial, Universitätsmedizin Berlin, Berlin, Germany Barcelona, Spain Lori Sokoll Hans Jørgen Nielsen Departments of Pathology and Oncology, Johns Hopkins Department of Surgical Gastroenterology, Hvidovre Hospital, Medical Institutions, Baltimore, MD Copenhagen, Denmark Barry R. Hoffman Harry Rittenhouse Department of Pathology and Laboratory Medicine, Gen-Probe Inc, San Diego, CA Mount Sinai Hospital, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Axel Semjonow Ontario, Canada Prostate Center, Department of Urology, University Clinic Muenster, Muenster, Germany Eleftherios P. Diamandis Department of Pathology and Laboratory Medicine, Ie-Ming Shih Mount Sinai Hospital, and Department of Laboratory Departments of Pathology and Oncology, Johns Hopkins Medicine and Pathobiology, University of Toronto, Medical Institutions, Baltimore, MD Ontario, Canada Tumor Markers.qxd 6/22/10 7:51 PM Page iv Copyright © 2009 by the American Association for Clinical Chemistry, Inc. All rights reserved. Single copies for personal use may be printed from authorized Internet sources such as the NACB’s home page (http://www.aacc.org/members/nacb/LMPG/Pages/default.aspx), provided it is printed in its entirety, including this notice. Printing of selected portions of the document is also permitted for personal use, provided the user also prints and attaches the title page and cover pages to the selected reprint or otherwise clearly identifies the reprint as having been produced by the NACB. Otherwise, this document may not be reproduced in whole or in part, stored in a retrieval system, translated into another language, or transmitted in any form without express written permission of the National Academy of Clinical Biochemistry. Such permission may be requested from NACB, 1850 K Street, Suite 625, Washington, DC, 20006-2213. Permission will ordinarily be granted, provided the NACB logo and the following notice appear prominently at the front of the document: Reproduced (translated) with permission of the National Academy of Clinical Biochemistry, Washington, DC. This document (PID 5693) was approved by the National Academy of Clinical Biochemistry Board of Directors in July 2008. The NACB is the Academy of the American Association for Clinical Chemistry. Tumor Markers.qxd 6/22/10 7:51 PM Page v Table of Contents 1. Introduction 1 2. Tumor Markers in Testicular Cancer 3 3. Tumor Markers in Prostate Cancer 15 4. Tumor Markers in Colorectal Malignancy 27 5. Tumor Markers in Breast Cancer 37 6. Tumor Markers in Ovarian Cancer 51 References 61 Acknowledgment 80 Appendix 81 iv Tumor Markers.qxd 6/22/10 7:51 PM Page vi Tumor Markers.qxd 6/22/10 7:51 PM Page 1 Chapter 1 Introduction We present to clinical chemists, clinicians, and other practition- the NACB web site (2) and as an Appendix to this document. ers of laboratory and clinical medicine the latest update of the As might be expected, many of the NACB recommendations National Academy of Clinical Biochemistry (NACB) Laboratory are similar to those made by other groups, as is made clear from Medicine Practice Guidelines (LPMG) for the use of tumor the tabular comparisons presented for each malignancy (2). In markers in testicular, prostate, colorectal, breast, and ovarian order to prepare these guidelines, the literature relevant to the cancers. These guidelines are intended to encourage more ap- use of tumor markers was reviewed. Particular attention was propriate use of tumor marker tests by primary care physicians, given to reviews including the few relevant systematic reviews hospital physicians and surgeons, specialist oncologists, and and to guidelines issued by expert panels. Where possible, these other health professionals. consensus recommendations of the NACB panels were evidence Clinical practice guidelines are systematically developed based. The Tumor Markers: Quality Requirements LMPG pre- statements to assist practitioners and patients to make decisions sents NACB recommendations relating to general quality about appropriate health care for specific clinical circumstances requirements for tumor measurements, and includes tabulation (1). An explanation of the methodology used when developing of important causes of false positive tumor marker results (eg, these Guidelines appears in the introduction of the Tumor due to heterophilic antibody interference, “high dose hooking”) Markers: Quality Requirements LMPG, which can be found on which must also be taken into account (3). 1 Tumor Markers.qxd 6/22/10 7:51 PM Page 2 Tumor Markers.qxd 6/22/10 7:51 PM Page 3 Chapter 2 Tumor Markers in Testicular Cancers Ulf-Håkan Stenman, Rolf Lamerz, and Leendert H. Looijenga BACKGROUND delayed until after chemotherapy in individuals with life- threatening metastatic disease. After orchiectomy, additional Approximately 95% of all malignant testicular tumors are of therapy depends on the type and stage of the disease. Surveillance germ cell origin, most of the rest being lymphomas, Leydig or is increasingly used for seminoma patients with stage I disease, Sertoli cell tumors and mesotheliomas. Germ cell tumors of ado- but radiation to the retroperitoneal and ipsilateral pelvic lymph lescents and adults are classified into two main types, semino- nodes, which is standard treatment for stage IIa and IIb disease, mas and nonseminomatous germ cell cancers of the testis is also used, as is short (single) course carboplatin (12). About (NSGCT). Testicular cancers represent about 1% of all malig- 4% to 10% of patients relapse with more than 90% of these cured nancies in males, but they are the most common tumors in men by chemotherapy. About 15% to 20% of stage I seminoma under age 15 to 35 years. They represent a significant cause of death surveillance relapse and need to be treated with chemotherapy. in this age group in spite of the fact that presently more than Patients with stage I nonseminomatous tumors are treated by 90% of the cases are cured (4). Germ cell tumors may also orchiectomy. After orchiectomy, surveillance and nerve-sparing originate in extragonadal sites (eg, the sacrococcygeal region, retroperitoneal lymph-node dissection are accepted treatment mediastinum, and pineal gland (5)). Those of the sacrum are options. About 20% of patients under