Management of Cancer in the Older Patient

Management of

CANCER

IN THE OLDER PATIENT Arash Naeim, MD PhD

Director of Geriatric Oncology Director of the Hematology-Oncology Fellowship Program Divisions of Hematology-Oncology and Geriatric Medicine Associate Professor, David Geffen School of Medicine University of California Los Angeles Los Angeles, California

David B. Reuben, MD

Director, Multicampus Program in Geriatric Medicine and Gerontology Chief, Division of Geriatrics Archstone Professor of Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles, California

Patricia A. Ganz, MD

Professor, David Geffen School of Medicine School of Public Health University of California Los Angeles Director, Division of Cancer Prevention and Control Research Jonsson Comprehensive Cancer Center Los Angeles, California

1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

MANAGEMENT OF CANCER IN THE OLDER PATIENT ISBN: 978-1-4377-1398-5 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notice Knowledge and best practice in this field are constantly changing. As new research and experience broaden our ­understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current ­information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data Management of cancer in the older patient / [edited by] Arash Naeim, David B. Reuben, Patricia A. Ganz. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4377-1398-5 (hardback : alk. paper) 1. Geriatric oncology. I. Naeim, Arash. II. Reuben, David B. III. Ganz, Patricia. [DNLM: 1. Neoplasms—therapy. 2. Aged. QZ 266] RC281.A34M36 2012 618.97′6994—dc23  2011016975 Acquisitions Editor: Kate Dimock Developmental Editor: Kate Crowley Publishing Services Manager: Hemamalini Rajendrababu Senior Project Manager: Srikumar Narayanan Designer: Ellen Zanolle

Printed in China Last digit is the print number: 9  8  7  6  5  4  3  2  1

To Arya and Shayan for their inspiration. My hope is that I can be nearly as good a father to you as my dad is to me. To all those older individuals with cancer who have taught me that life is richer when living with dignity, ­quality, and passion. Arash Naeim

For all my older patients, friends, and family members who have fought their battles with cancer. David Reuben

Thanks to my family for the love and support and especially to my parents and my husband’s parents who have taught us so much about aging and its impact on health and quality of life. Patricia Ganz

CONTRIBUTORS Sunil Amalraj, MD Geriatric-Oncology Fellow Divisions of Hematology and Geriatric Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles, California

Melissa Cohen, MD Geriatric-Oncology Fellow Divisions of Hematology and Geriatric Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles, California

Lodovico Balducci, MD Professor of Oncologic Sciences University of South Florida College of Medicine Medical Director of Affiliates and Referring Physician Relations Program Leader of Senior Adult Oncology Moffitt Cancer Center Tampa, Florida

Jennifer M. Croswell, MD, MPH Acting Director Office of Medical Applications of Research National Institutes of Health Bethesda, Maryland

Daniel Becker, MD General Medicine, Geriatrics and Palliative Care University of Virginia Health System Charlottesville, Virginia Susan Charette, MD Assistant Professor of Medicine, Geriatrics Department of Medicine University of California Los Angeles Los Angeles, California Octavio Choi, MD, PhD Department of Psychiatry Department of Medicine University of California Los Angeles Los Angeles, California Kerri M. Clough-Gorr, DSc, MPH National Institute for Cancer Epidemiology and Registration (NICER) Institute of Social and Preventive Medicine (ISPM) University of Zürich Zürich, Switzerland Institute of Social and Preventive Medicine (ISPM) University of Bern Bern, Switzerland Section of Geriatrics Boston University Medical Center Boston, Massachusetts

Lucia Loredana Dattoma, MD Geriatric Medicine Ronald Reagan UCLA Medical Center Santa Monica UCLA Medical Center and Orthopaedic Hospital Stewart and Lynda Resnick Neuropsychiatric Hospital University of California Los Angeles Los Angeles, California

William B. Ershler, MD Deputy Clinical Director Intramural Research Program National Institute on Aging National Institutes of Health Bethesda, Maryland Randall Espinoza, MD, MPH Professor Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine University of California Los Angeles Director Geriatric Psychiatry Fellowship Training Program Medical Director ECT Program Associate Director Center on Aging University of California Los Angeles Los Angeles, California

James W. Davis Jr., MD Clinical Professor Division of Geriatrics University of California Los Angeles Los Angeles, California

Betty Ferrell, PhD, MA, FAAN, FPCN Professor and Research Scientist Nursing Research and Education Department of Population Sciences City of Hope Comprehensive Cancer Center Duarte, California

Roxana S. Dronca, MD Assistant Professor of Oncology Instructor in Medicine Department of Oncology Mayo Clinic Rochester, Minnesota

Bruce Ferrell, MD Professor of Medicine/Geriatric Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles, California

Amy A. Edgington, RN, NP-BC Division of Cancer Prevention and Control Research Jonsson Comprehensive Cancer Center David Geffen School of Medicine School of Public Health University of California Los Angeles Los Angeles, California

Patricia A. Ganz, MD Professor David Geffen School of Medicine School of Public Health University of California Los Angeles Director, Division of Cancer Prevention and Control Research Jonsson Comprehensive Cancer Center Los Angeles, California

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CONTRIBUTORS

Barbara A. Given, PhD, RN, FAAN University Distinguished Professor Associate Dean of Research and Doctoral Program College of Nursing Michigan State University East Lansing, Michigan Charles W. Given, PhD Professor Department of Family Medicine College of Human Medicine Michigan State University East Lansing, Michigan Erin E. Hahn, MPH Division of Cancer Prevention and Control Research Jonsson Comprehensive Cancer Center David Geffen School of Medicine School of Public Health University of California Los Angeles Los Angeles, California David M. Heimann, MD Assistant Professor of Surgery Mt. Sinai School of Medicine Surgical Oncologist Queens Cancer Center Jamaica, New York Dawn L. Hershman, MD, MS Assistant Professor of Medicine and Epidemiology Co-Director Breast Cancer Program Herbert Irving Comprehensive Cancer Center Department of Medicine Columbia University New York, New York Arti Hurria, MD Associate Professor Department of Medical Oncology and Experimental Therapeutics and Cancer Control and Population Sciences Program Director Cancer and Aging Research Program City of Hope Comprehensive Cancer Center Duarte, California William Irvin Jr., MD Assistant Professor of Medicine University of North Carolina at Chapel Hill Division of Hematology/Oncology Lineberger Comprehensive Cancer Center Chapel Hill, North Carolina

Michael R. Irwin, MD Norman Cousins Professor of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine Professor of Psychology College of Letters and Sciences Director Cousins Center for Psychoneuroimmunology Semel Institute for Neuroscience University of California Los Angeles Los Angeles, California Pattie Jakel, RN, MN, AOCN Clinical Nurse Specialist Clinical Research Center University of California Los Angeles Los Angeles, California Bindu Kanapuru, MD Clinical Research Fellow Clinical Research Branch National Institute on Aging National Institutes of Health Baltimore, Maryland M. Margaret Kemeny, MD, FACS Professor of Surgery Mt. Sinai School of Medicine Director Queens Cancer Center Jamaica, New York Barnett S. Kramer, MD, MPH Editor-in-Chief Journal of the National Cancer Institute Data Query (PDQ) Screening and Prevention Editorial Board Rockville, Maryland Associate Director for Disease Prevention Office of Disease Prevention National Institutes of Health Bethesda, Maryland Stuart M. Lichtman, MD Attending Physician Clinical Geriatrics Program Memorial Sloan-Kettering Cancer Center New York, New York Charles Loprinzi, MD Regis Professor of Breast Cancer Research Division of Medical Oncology Mayo Clinic Rochester, Minnesota

CONTRIBUTORS Jeffrey Mariano, MD Assistant Clinical Professor of Medicine/Geriatric Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles, California Susan McCloskey, MD Department of Radiation Oncology Ronald Reagan UCLA Medical Center Santa Monica UCLA Medical Center and Orthopaedic Hospital University of California Los Angeles Los Angeles, California Joseph Albert Melocoton, RN, MSN, OCN Oncology Nurse Practitioner Wilshire Oncology Medical Group, Inc. Pasadena, California Lillian C. Min, MD Assistant Professor Department of Internal Medicine University of Michigan Ann Arbor, Michigan Hyman B. Muss, MD Professor of Medicine University of North Carolina at Chapel Hill Director of Geriatric Oncology Lineberger Comprehensive Cancer Center Chapel Hill, North Carolina Arash Naeim, MD PhD Director of Geriatric Oncology Director of the Hematology-Oncology Fellowship Program Divisions of Hematology-Oncology and Geriatric Medicine Associate Professor David Geffen School of Medicine University of California Los Angeles Los Angeles, California Sumanta Kumar Pal, MD Assistant Professor Division of Genitourinary Malignancies Department of Medical Oncology and Experimental Therapeutics City of Hope Comprehensive Cancer Center Duarte, California Janet Pregler, MD Professor of Clinical Medicine Director Iris Cantor–UCLA Women’s Health Center David Geffen School of Medicine University of California Los Angeles Los Angeles, California

Scott D. Ramsey, MD, PhD Associate Professor of Medicine and Health Services Associate Member Cancer Prevention Research Program Fred Hutchinson Cancer Research Center Division of General Internal Medicine University of Washington Seattle, Washington David B. Reuben, MD Director Multicampus Program in Geriatric Medicine and Gerontology Chief Division of Geriatrics Archstone Professor of Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles, California Lisa M. Schwartz, MD Medical Director Integrative Medicine Roy and Patricia Disney Family Cancer Center Providence Saint Joseph Medical Center Burbank, California John F. Scoggins, PhD, MS Senior Research Fellow Fred Hutchinson Cancer Research Center University of Washington Seattle, Washington Mary E. Sehl, MD, PhD Physician Divisions of Geriatrics and Hematology-Oncology David Geffen School of Medicine University of California Los Angeles Los Angeles, California Veena Shankaran, MD Assistant Professor Medical Oncology Assistant Member Clinical Research Division Fred Hutchinson Cancer Research Center University of Washington Seattle, Washington Paula Sherwood, PhD, RN, CNRN Associate Professor University of Pittsburgh School of Nursing Pittsburgh, Pennsylvania

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x

CONTRIBUTORS

Rebecca A. Silliman, MD, PhD Professor Department of Medicine Department of Epidemiology Boston University School of Medicine Boston, Massachusetts Michael L. Steinberg, MD Professor and Chair Department of Radiation Oncology David Geffen School of Medicine University of California Los Angeles Los Angeles, California Virginia Sun, RN, PhD Assistant Research Professor Division of Nursing Research and Education Department of Cancer Control and Population Sciences City of Hope Duarte, California Tiffany A. Traina, MD Assistant Attending Physician Breast Cancer Medicine Service Memorial Sloan-Kettering Cancer Center New York, New York Anne Walling, MD Ronald Reagan UCLA Medical Center Santa Monica UCLA Medical Center and Orthopaedic Hospital University of California Los Angeles Los Angeles, California Peter Ward, MD Geriatric-Oncology Fellow Divisions of Hematology and Geriatric Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles, California

Neil S. Wenger, MD, MPH Professor of Medicine Director UCLA Health System Ethics Center Chair Ethics Committee Ronald Reagan UCLA Medical Center Santa Monica UCLA Medical Center and Orthopaedic Hospital University of California Los Angeles Los Angeles, California Elizabeth Whiteman, MD Department of Geriatric Medicine University of California Los Angeles Los Angeles, California Jeffrey Wu, MD Division of Radiation Oncology David Geffen School of Medicine University of California Los Angeles Los Angeles, California Jerome W. Yates, MD, MPH Senior Vice President Population Sciences and Health Services Research Roswell Park Cancer Institute Professor of Medicine State University of New York at Buffalo Buffalo, New York Marjorie G. Zauderer, MD Hematology-Oncology Fellow Department of Medicine Memorial Sloan-Kettering Cancer Center New York, New York

PREFACE The population is aging. It is estimated that 1 in 5 individuals will be older than 65 years by the year 2030. The risk of cancer increases with age, with persons older than age 75 having the highest risk. Individuals older than age 65 also account for greater than two thirds of all cancer deaths. The demand for cancer care will steadily grow, but workforce projections for the next decade demonstrate that the supply of oncologists will not meet this demand. Therefore it is critically important for primary care providers (general practitioners, family practitioners, internists, and nurse practitioners) to become more familiar with the Management of Cancer in the Older Patient. A frequent comment among general oncologists is that they mostly see older individuals, a viewpoint supported by the epidemiologic data. It is important to note that most of the evidence supporting treatment recommendations in oncology is derived from clinical trials where older individuals were significantly underrepresented. Moreover, those older individuals who did participate in clinical trials usually represented a healthy cohort with minimal competing comorbid conditions and little impairment in physical functioning. As a result, it is often hard to know how to generalize the evidence base to everyday practice or apply it to the average older patient with cancer. Older individuals tend to be a more heterogeneous population. Although only 1 in 10 individuals has a functional impairment between the ages of 65 and 74, this number increases to almost half for patients over the age of 85. Similarly, as individuals age, the number of other co-existing conditions (comorbidity) increases as well, with individuals over the age of 75 having, on average, 5 other health conditions. Age, functional status, and comorbidity alter the lens through which providers view the older patient with cancer. These perceptions affect their approach to screening and prevention, diagnosis, treatment, supportive care, and survivorship care. In these areas, the role of the primary care provider extends beyond just screening, diagnosis, and referral to also include comanagement, aftercare, and long-term surveillance. In parallel to the clinical practice of cancer care, the field of oncology is quickly being transformed. There is a large growth of research in molecular and cell biology, as well as immunology. Over the last decade, numerous new targeted therapies have received approval from the Food and Drug Administration. These newer therapies often have a more pronounced therapeutic effect but have different side effect profiles than traditional

chemotherapy. There is an increasing trend toward personalizing or individualizing treatment based on the underlying biology of the individual and/or the tumor. In older patients with cancer, it will be important to combine these advances with the recognition that host factors that are markers for frailty also need to be factored into the process of individualizing care. The drug advances in cancer care are also associated with the high cost of treatment, which, when combined with increasingly large numbers of elderly patients, will put a strain on the resources allocated to health care. The Management of Cancer in the Older Patient examines the key issues that a primary care provider would encounter in providing and supporting the care of an older patient. The book is divided into six sections. Section I, Screening/Prevention, examines key guidelines for screening and discusses populations for which screening may be underutilized or overutilized. Section II, Diagnosis/Assessment, examines diagnostic workup, assessment (geriatric assessment, functional assessment, and comorbidity), as well as the value of a second opinion. Section III, Treatment, examines modalities of treatment (surgery, radiation, and chemotherapy) with special chapters on novel and targeted therapies, clinical trials in the elderly, and shared treatment decision making. Section IV is focused entirely on supportive care with special chapters on insomnia and complementary and alternative care. Section V focuses on rehabilitation, surveillance, and survivorship. Section VI, the last section, examines important issues including home care, caregiver burden, communication, end of life and hospice, ethical issues, and economic issues important to managing the older cancer patient. Most of the chapters in Management of Cancer in the Older Patient are case based with the use of summary and key tables to help synthesize the information. Whenever possible, we have included a suggested reading list that may be valuable to the reader. The goal of this book is to take a multidisciplinary approach to traditional topics such as prevention, screening, diagnosis, treatment, and survivorship while applying a geriatric lens to these issues, focusing on functioning, assessment, frailty, quality of care, quality of life, caregivers, and cost. Our hope is that this book makes a very practical contribution to improve the decision-making process of primary care providers, who often serve as the central resource or “quarterback” in the care of older complex patients. The editors are excited to contribute to a field that will be increasingly important as the number of older Americans with cancer rises dramatically in the coming decades.

xi

ACKNOWLEDGMENTS There are many people who contributed to this book project. First, I would like to thank my father who is a great role model and shared his experiences associated with the several books he has published to date. This book would not exist without the tremendous efforts of the Elsevier publishing and editorial team. Mara Conner went out of her way to help me find the right home for this book and connecting me to Druanne Martin, who was the force to get this book proposed and approved at Elsevier. Along the way this book was shepherded by many individuals including Dolores Meloni and Taylor Ball. The team that did the heavy lifting in the end to put this book together at Elsevier included ­Srikumar Narayan (Senior Project Manager),

xii

Kate Crowley (Editorial Assistant), and Kate Dimock (Senior Acquisitions Editor). I would also like to thank the individuals at Elsevier who worked behind the scenes to make this book possible, including Patricia Tannian, ­Ellen Zanolle, Lesley Frazier, Cara Jespersen, Hemamalini Rajendrababu, and Claire Kramer. I really appreciate the help of all the staff and team at Elsevier. I would like to thank my own assistant, Chelsea Starkweather, who spent countless hours reading through the chapters of this book and providing editorial suggestions. Lastly, I would like to thank my co-editors, who placed their faith and time in this project. Arash Naeim

CHAPTER

1

The Epidemiology of Cancer and Aging Kerri M. Clough-Gorr and Rebecca A. Silliman

Aging, a highly individualized process, is known to be related to changes in the physical, cognitive, emotional, social, and economic status of older adults. Increasing age is primarily associated with negative changes in these areas (e.g., increased comorbidity, decreased function, limited social support). These age-associated changes may occur singly or in combination, with broad variation among older adults. Moreover, they often result in considerable consequences not just for aging individuals themselves but simultaneously for health care systems, families, and caregivers. A common late-life experience is a cancer diagnosis. According to the National Cancer Institute (NCI), aging is the most important risk factor for cancer, with most cancers occurring in persons aged 65 years and older. Over the last several decades, cancer trends have been changing contemporaneously with our knowledge of aging. Because of the increased heterogeneity of older populations, treating older cancer patients seldom means treating only the cancer. Furthermore, with improved screening and treatments, larger numbers of older cancer patients are experiencing longer-term survival. Unfortunately, even though older adults make up the largest segment of the cancer population, they are often undertreated and are seldom included in clinical trials. Few clinical trials are even designed to identify optimal treatments for them. The combined effects of cancer and aging are of concern because of graying populations worldwide (a larger proportion aging in industrialized countries; greater numbers aging in developing countries). Although we cannot truly anticipate the changes that rapid population aging will bring, we can attempt to understand the epidemiological patterns of aging and cancer, where they intersect, and their potential implications. Such understanding will provide a frame of reference to address agerelated disparities in research, education, and treatment in the older adult cancer population. Because of growing numbers alone, it is certain that management of cancer in older adults will continue to be a complex, resourceintensive, and increasingly common problem.

What follows herein is an overview of topics pertaining to the epidemiology of cancer and aging. Trends in cancer incidence and mortality are examined, and the specific characteristics and unique issues related to older cancer patients are described. Special attention is provided to the survivorship experience of older cancer patients, along with a summary of the challenges associated with studying them.

INCIDENCE AND MORTALITY: THEN AND NOW There have been remarkable changes in the United States population over the last century. One hallmark of these changes is the expansion of the older (65 years and older) population (Figure 1-1).1 U.S. Census Bureau estimates show that the percentage of Americans 65 years and older has more than tripled (from 4.1% in 1900 to 12.8% in 2008). The older population itself is getting older; in 1940, 4.1% of the older population was 85 years or older (the “oldest old”), whereas in 2008, 14.7% was in this group. This trend toward greater longevity is reflected by tremendous growth in the centenarian population (approximately 120% from 1990 to 2008) and the current life expectancy estimates of older adults (Figure 1-2).5,7 After the middle of the twentieth century, life expectancy at age 65 years increased moderately (5 years for men, 8 years for women) relative to life expectancy gains at birth. In recent years (1990 to 2005), the gap in life expectancy between older white and black people has been stable and narrower than at birth (difference at age 65 years approximately 2 years for men and 1 year for women).8 These aging trends will hasten with the senescence of the Baby Boom generation, but, on the basis of previous life expectancies, not necessarily uniformly across sex and race/ethnicity. The number of older Americans is expected to more than double by 2050 (increasing from 39 million in 2008 to 89 million) with substantial growth in older minority segments (Figure 1-3) and increasingly in female “oldest-olds.”2 The U.S. Census 3

CHAPTER 1  The Epidemiology of Cancer and Aging

4

Millions 100 90 80 70 60 50 40

65 and over

30 20 85 and over

10

0 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 2006 Projected

FIGURE 1-1  Number of people age 65 and older in the United States, by age group, selected years 1900-2006 and projected 2010-2050. (Adapted from U.S. Department of Health and Human Services: A Profile of Older Americans: 2008. Washington, DC: Administration on Aging, 2008.)

Life expectancy for women 25 21.3

15.7

15

17 11.9

13

9.5

10

80

6.8

0

9.6

8.6

70

75

80

85

4.8

3.9

2.9

2.7 1.1

1.8

90

95

Life expectancy for men 25

Years

20 15

70

Black female

White male Black male

14.2 12.4

10

9.3 6.7

0

75

65

18

4.9

5

B

White female

5.8

5.9

4.6

5

A

85

Age in years

Years

20

Top 25th percentile 50th percentile Lowest 25th percentile

70

75

60

10.8 7.9

6.7 3.3

80

5.8

4.7

85 Age, y

2.2

3.2

90

4.3 1.5

2.3

1

0 1970

1980

1990

2000

2006

95

FIGURE 1-2  Life expectancy of older adults in the United States A, Upper, middle, and lower quartiles of life expectancy by sex at selected ages. (Adapted from Walter LC, Covinsky KE. Cancer screening in elderly patients: a framework for individualized decision making. JAMA 2001;285:2750-6.) B, Life expectancy for women and men by race 1970-2006. (Adapted from Heron et  al. Deaths: final data for 2006. National Vital Statistics Reports; Vol 57, No 14. Hyattsville, MD: National Center for Health Statistics; 2009.)

Bureau also projects by 2050 a nearly 225% increase in persons aged 100 years and older (from 2008) and that, for the first time in United States history, the population older than 65 years will outnumber the population younger than 15 years. Figure 1-4 shows the overall

projected age shift in the U.S. population pyramid from 2000 to 2050.2 As older Americans live longer than ever before, the inevitable shift in the population age structure foreshadows many challenges. Importantly, whether or

CHAPTER 1  The Epidemiology of Cancer and Aging

5

Percent 100 2006 2050 (projected)

90 80

81

70 60

61

50 40 30 18

20 9

10 0

12 3

Non-Hispanic white alone

Black alone

8 1

Asian alone

3

All other races alone or in combination

6 Hispanic (of any race)

FIGURE 1-3  United States population age 65 and older by race and Hispanic origin, selected years 2006 and projected 2050. (Adapted from U.S. Department of Health and Human Services: A Profile of Older Americans: 2008. Washington, DC: Administration on Aging, 2008.)

not years added later in life are healthy, enjoyable, and productive depends in large part on prevention and control of potentially debilitating and sometimes fatal chronic diseases such as cancer. Figure 1-5 shows that cancer is the fourth most common chronic disease and the second leading cause of death in older adults in the United States.1 Cancer is a disease that disproportionately affects older adults. Over the past decades, cancer incidence and mortality trends in the oldest population showed a greater burden than for those in the so-called young-old (65 to 74 years) and younger populations (Figure 1-6).3 The increased risk of cancer in older adults is proposed to be related to two main age-linked processes. Because cancer is a multistep process, over the course of longer lives there is both increased opportunity for DNA damage and longer exposure to potential carcinogens. Older adults, therefore, may have greater potential for accrued molecular damage coexisting with age-related decreased cellular repair activity leading to malignancies. This is supported by the epidemiological evidence, which consistently shows at least twofold or higher all-cause cancer mortality and incidence rates in older adults since SEER reporting began in 1975. From 2002 to 2006, the median age at diagnosis for cancer of all sites was 66 years.9 However, looking at more finely stratified older age groups during the same period, approximately 24.9% of all cancers were diagnosed between 65 and 74 years, 22.2% between 75 and 84 years, and 7.6% at 85 years of age and older. These patterns hold across most primary cancer types. Within the older age groups, controversies exist over evidence pointing to a potential drop of cancer incidence and mortality in the oldest-old group. These data raise unresolved questions as to whether the effect is real and, if so, whether it is due to selective survival, an interaction with late-life biology, or both.

Trends in recent years in the older U.S. population show decreases in age-adjusted all-cause cancer mortality and incidence (−1.1 and −1.2 annual percent change 1997 to 2006, respectively).3,6 However, trends and risks vary considerably by primary cancer site and sex (Figure 1-7 and Table 1-1).6,10 In people 65 years of age and older, lung cancer incidence and mortality increased for women and decreased for men. Nonetheless, it was the second leading cancer site and the most fatal cancer (approximately 30% of all cancer deaths) in both women and men. The second- and third-ranked fatal cancers were breast and colorectal cancers in women and colorectal and prostate cancers in men. All showed varied but decreased mortality and incidence over time. The risk of colorectal cancer rose precipitously with age, with 91% of cases diagnosed in individuals aged 50 years of age and older, with moderate decreases in mortality and incidence (−2.9 and −3.0 annual percent change 1997 to 2006, respectively).6,9,10 There are also considerable differences in cancer burden and survival across race and ethnic populations (Figures 1-8 and 1-9).4,6 All-cause cancer incidence and mortality rates have been higher, and relative survival rates lower, for African-Americans in comparison to whites. Hispanic, Asian, Pacific Islander, American Indian, and Alaska Native persons generally have lower incidence rates than whites, except for several specific cancers (e.g., stomach, liver, cervix, kidney, and gallbladder). This general pattern of lower incidence among racial and ethnic minorities has been attributed to younger age structures. However, cancer disparities in incidence, mortality, and late-stage presentation also exist within these groups by geography, national origin, economic status, and other factors. By 2050 and beyond, these disparities are expected to transition into the older age groups as demographic changes (i.e., growth in older Text continued on p. 10

CHAPTER 1  The Epidemiology of Cancer and Aging

6

Age 100 and over 95 to 99 90 to 94 85 to 89 80 to 84 75 to 79 70 to 74 65 to 69 60 to 64 55 to 59 50 to 54 45 to 49 40 to 44 35 to 39 30 to 34 25 to 29 20 to 24 15 to 19 10 to 14 5 to 9 Under 5 5.0

4.5

4.0

3.5

3.0

2.5

2.0

A

1.5

1.0

0.5

Male

0.0 0.5 Percent

1.0

0.0 0.5 Percent

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

2.0

2.5

3.0

3.5

4.0

4.5

5.0

Female

Age 100 and over 95 to 99 90 to 94 85 to 89 80 to 84 75 to 79 70 to 74 65 to 69 60 to 64 55 to 59 50 to 54 45 to 49 40 to 44 35 to 39 30 to 34 25 to 29 20 to 24 15 to 19 10 to 14 5 to 9 Under 5 5.0

B

4.5

4.0

3.5

3.0

2.5

2.0

1.5 Male

1.0

0.5

1.5 Female

FIGURE 1-4  Population pyramids of the United States (left) 2000 and (right) projected 2050. (Adapted from U.S. Census Bureau: Projections of the Population by Age and Sex for the United States: 2010 to 2050 (NP2008-T12). Washington, DC: Population Division, U.S. Census Bureau; 2008.)

CHAPTER 1  The Epidemiology of Cancer and Aging

7

PERCENTAGE OF PEOPLE AGE 65 AND OVER WHO REPORTED HAVING SELECTING CHRONIC CONDITIONS, BY SEX, 2005–2006 Percent 100

Men Women

90 80 70 60

52 54

54

50

43 37

40 30

26

24

20 10 0

Heart disease

Hypertension

10 8

10 12

11 10

Stroke

Asthma

Chronic bronchitis or Emphysema

19

19 17

Any cancer

Diabetes

Arthritis

Note: Data are based on a 2-year average from 2005–2006. Reference population: These data refer to the civilian noninstitutionalized population. Source: Centers for Disease Control and Prevention, National Center for Health Statistics, National Health Interview Survey.

A

DEATH RATES FOR SELECTED LEADING CAUSES OF DEATH AMONG PEOPLE AGE 65 AND OVER, 1981–2004 ICD-10

Per 100,000 3,000 2,750 2,500 2,250

Diseases of heart

2,000 1,750 1,500

Malignant neoplams

1,250 1,000 750

Cerebrovascular disease Chronic lower respiratory disease Influenza and pneumonia Diabetes mellitus

500 250 0 1981

1985

1990

1995

Alzheimer’s disease

2000

2004

Note: Death rates for 1981–1998 are based on the 9th revision of the International Classification of Diseases (ICD-9). Starting in 1999, death rates are based on ICD-10 and trends in death rates for some causes may be affected by this change.11 For the period 1981–1998, causes were coded using ICD-9 codes that are most nearly comparable with the 113 cause list for the ICD-10 and may differ from previously published estimates. Rates are age adjusted using the 2000 standard population. Reference population: These data refer to the resident population. Source: Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

B FIGURE 1-5  Incidence and mortality of chronic conditions in the population aged 65 and older in the United States. A, Percentage of popu-

lation 65 years and older, by chronic condition and sex, 2005-2006. B, Mortality rates in population 65 years and older, by leading causes of death, 1981-2004. (Adapted from U.S. Department of Health and Human Services: A Profile of Older Americans: 2008. Washington, DC: Administration on Aging, 2008.)

AGE-ADJUSTED U.S. MORTALITY RATES BY AGE AT DIAGNOSIS/DEATH ALL SITES, ALL RACES, BOTH SEXES 1975–2006

AGE-ADJUSTED SEER INCIDENCE RATES BY AGE AT DIAGNOSIS/DEATH ALL SITES, ALL RACES, BOTH SEXES 1975–2006 (SEER 9)

2500

3500 Ages 20-49 Ages 65-74

Ages 20-49 Ages 65-74

Ages 50-64 Ages 75+

Ages 50-64 Ages 75+

3000

2000

Rate per 100,000

Rate per 100,000

2500 1500

1000

2000

1500

1000 500 500

Year of death

Cancer sites include invasive cases only unless otherwise noted. Mortality source: US Mortality Files, National Center for Health Statistics, CDC. Rates are per 100,000 and are age-adjusted to the 2000 US Std Population (19 age groups Census P25-1130). Regression lines are calculated using the Joinpoint Regression Program Version 3.3.2, June 2008, National Cancer Institute.

06 20

00 20

95 19

90 19

85 19

80 19

75

B

19

06 20

00 20

95 19

90 19

85 19

80

0

19

A

19

75

0

Year of diagnosis

Cancer sites include invasive cases only unless otherwise noted. Incidence source: SEER 9 areas (San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah and Atlanta). Rates are per 100,000 and are age-adjusted to the 2000 US Std Population (19 age groups Census P25-1130). Regression lines are calculated using the Joinpoint Regression Program Version 3.3.2, June 2008, National Cancer Institute.

FIGURE 1-6  Trends of age-adjusted all-cause cancer mortality (left) and incidence (right) rates for the United States population, by age group, 1975-2006. (Adapted from FastStats: An interactive tool for access to SEER cancer statistics. Bethesda, MD, National Cancer Institute, 2009.) AGES 65 AND OVER Liver & intrahepatic bile duct Melanoma of the skin Thyroid Lung & bronchus (female) Esophagus Pancreas Kidney & renal pelvis Urinary bladder Ovary Corpus & uterus, NOS Leukemia Hodgkin lymphoma Brain & other nervous system Myeloma All cancer sites All sites except lung Larynx Lung & bronchus (male) Breast (female) Testis Oral cavity & pharynx Non-Hodgkin lymphoma Colon & rectum Cervix uteri Stomach Prostate

A

1.2* 1.1* 0.7 0.6* 0.5* 0.3* 0.1 –0.1 –0.1 –0.2 –0.4 –0.8 –0.9* –0.9* –1.1* –1.3* –1.5* –1.6* –1.6* –1.7 –1.8* –2.3* –2.9* –3.2* –3.5* –4.1*

–8 –6 –4 –2 0 2 4 6 8 Annual percent change, 1997–2006

Source: US Mortality Files, National Center for Health Statistics, Centers for Disease Control and Prevention. For sex-specific cancer sites, the population was limited to the population of the appropriate sex. * Underlying rates are per 100,000 and age-adjusted to the 2000 US Std Population (19 age groups - Census P25-1103). The Annual Percent Change is significantly different from zero (p70%) and AFP is elevated in yolk sac tumors. Also, hCG is elevated in choriocarcinomas and hence useful in diagnosing gestational trophoblastic tumors.66 The tumor marker CA-125, developed for epithelial ovarian cancer, is useful in distinguishing benign from malignant disease in postmenopausal women who pre­ sent with ovarian masses and elevated concentrations

37

of CA-125. One study found a CA-125 greater than 95 U/mL has a positive predictive value of 95% in a postmenopausal woman with a pelvic mass.67-68 A two-stage strategy in which ultrasonography is performed only if CA-125 concentrations are elevated has shown promise in detecting ovarian cancer. In a study of 4000 women, the specificity of CA-125 plus ultrasound was 99.9% compared with 98.3% for CA-125 alone.69 Neuroendocrine tumors constitute a heterogeneous group of rare cancers that originate from endocrine glands in various tissues such as the pituitary, parathyroid, and adrenal glands; the pancreas; and the respiratory tract.70 Tumor markers often play an important role in the detection of these tumors. For example, the diagnosis of pheochromocytoma usually is established by finding an increase in the urinary excretion of catecholamines or catecholamine metabolites such as vanillylmandelic acid (VMA) and homovanillic acid (HVA).71 The urinary serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) is the primary test for determining the overproduction of serotonin that is characteristic of carcinoid tumors.72 CASE 3-4      CONTINUED Elevation of the tumor marker α-fetoprotein (AFP) to 800 ng/mL, in the presence of a liver lesion greater than 2 cm in diameter, is sufficient for the diagnosis of hepatocellular carcinoma (HCC). The presence of classical arterial enhancement on triphasic CT further confirms this diagnosis. Tissue biopsy is not required to confirm the diagnosis in this case.64 The median age at diagnosis for HCC is 64, with 48% of cases occurring in people older than 65 years. The overall 5-year survival for the period 1999 to 2006 was 13.8%.3 Treatment options for this patient include liver transplantation, surgical resection, ablation (radiofrequency, cryoablation, microwave) and chemoembolization. Short- and long-term results for liver transplantation in patients older than 65 have found outcomes to be comparable to those younger than 65, if older candidates are carefully selected.73 (Table 3.4).

Summary Men in the United States have a one in two lifetime risk of developing cancer and women have a one in three lifetime risk of developing cancer. During the last 3 decades there has been steady improvement in the relative 5-year survival rate for all cancers, with a 50% survival from 1975-1977 improving to a 66% survival from 19962004.3 There has also been an increase in the incidence of certain cancers, such as breast cancer (4.3%) and prostate cancer (7.6 %), since 1975.8 The factors behind these two trends include advances in treatment, the aging population, and significant improvements in our ability to detect cancer at a less advanced stage. As a result of increasing life expectancy, the incidence of cancer is elevenfold higher in persons older than 65 years compared to those younger than 65.76 The development of imaging

CHAPTER 3  Approach to Cancer Diagnosis: Use of Radiology, Pathology, and Tumor Markers

38

TA B L E 3 - 4    Malignancies Associated with Elevated Tumor Marker Levels Tumor Marker

Primary Tumor

Screening

Normal Value

Benign disease unlikely

PSA

Prostate cancer

Benign conditions

Yes

10 ng/mL

Prostatitis, BPH

CA=125

Ovarian cancer

No

200 units/mL

No

500 ng/mL

No

30m mIU/mL

No

1000 units/mL

Colorectal cancer

Adenocarcinoma of unknown primary Selected pancreatic masses No

No