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VOLUME 24 䡠 NUMBER 32 䡠 NOVEMBER 10 2006
JOURNAL OF CLINICAL ONCOLOGY
R E V I E W
A R T I C L E
Enhancing Research on Cancer Survivors
John Z. Ayanian and Paul B. Jacobsen
From the Department of Medicine, Division of General Medicine and Primary
Care, Brigham and Women’s Hospital;
Department of Health Care Policy,
Harvard Medical School, Boston, MA;
Departments of Psychology and Interdisciplinary Oncology, University of
South Florida; and Health Outcomes
and Behavior Program, Moffitt Cancer
Center, Tampa, FL.
Submitted March 21, 2006; accepted
July 21, 2006.
Supported by Grants No. U01 CA93324
(J.Z.A.) and P20 CA103676 (P.B.J) from
the National Cancer Institute.
Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this
article.
Address reprint requests to John Z.
Ayanian, MD, MPP, Department of
Health Care Policy, Harvard Medical
School, 180 Longwood Ave, Boston,
MA 02115; e-mail: ayanian@
hcp.med.harvard.edu.
© 2006 by American Society of Clinical
Oncology
0732-183X/06/2432-5149/$20.00
DOI: 10.1200/JCO.2006.06.7207
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The United States devotes substantial resources to understanding the etiologies of cancer and improving
treatments, but much less research has focused on the needs of cancer survivors after they have completed
active treatment. This article augments findings from the Institute of Medicine about cancer survivorship
research and ways to enhance quality of life and quality of care. Studies of cancer survivors should focus on
mechanisms and risk factors for impaired quality of life and evaluate interventions to improve this domain.
Research to improve quality of care should concentrate on survivorship care plans, surveillance tests,
respective roles of primary and specialty care, and performance measures related to survivorship care.
Opportunities to expand research on cancer survivors include clinical trials, large cohort studies, cancer
registries, and national surveys. Research to understand the needs of cancer survivors will provide a
foundation for effective programs to meet these needs.
J Clin Oncol 24:5149-5153. © 2006 by American Society of Clinical Oncology
INTRODUCTION
More than 10 million people alive today in the
United States have been diagnosed with cancer.
Most of them have completed active cancer treatments, and nearly two thirds of cancer survivors
have survived more than 5 years since they were
initially diagnosed with cancer.1 Although the
United States devotes enormous research resources
to understanding the etiologies of cancer and improving cancer treatments, much less research has
focused on the needs and care of cancer survivors
after they have completed active treatment.
The Institute of Medicine recently issued a major report, From Cancer Patient to Cancer Survivor:
Lost In Transition.1 This report provided a comprehensive assessment of the health needs of cancer
survivors and the currently fragmented approaches
to serving them. The report also included 10 recommendations to improve the quality of life and quality
of care for cancer survivors. As the capstone of the
report, the 10th recommendation emphasized that
federal and private organizations “should increase
their support of survivorship research and expand
mechanisms for its conduct. New research initiatives focused on cancer patient follow-up are urgently needed to guide effective survivorship care.”
The Institute of Medicine has specified four
essential components of survivorship care that are
important targets for greater research: prevention of
recurrent or new cancers and the late effects of prior
cancer and its treatment; surveillance for recurrent
or new cancers that can be treated more effectively if
detected early; interventions to alleviate physical and
psychological symptoms that persist or occur be-
yond active cancer treatment and to improve quality
of life; and coordination of primary and specialty
care to address multiple conditions and needs.
The purpose of this article is to feature and
expand on the findings from the Institute of Medicine about the current state of cancer survivorship
research and ways to enhance it. Researchers who
study cancer patients and clinicians who care for
cancer patients can play a leading role in refining the
priorities of this research agenda and moving it
forward. By highlighting survivorship research
priorities and opportunities for the oncology
community to contribute to this effort, our goal is
to stimulate greater attention and action to improve the care of the vast numbers of Americans
who are cancer survivors.
IMPROVING QUALITY OF LIFE FOR
CANCER SURVIVORS
In recent years, research on quality of life in cancer
survivors has increased steadily. Using Medline as a
metric, 40 articles published in 1994 were indexed
under the combination of “quality of life,” “neoplasms,” and “survivors”; in 2004, this number had
increased to 126 publications. The growing number
of publications is consistent with the increasing recognition that end points other than survival and
disease-free survival are important to consider when
evaluating the effectiveness of cancer treatments.
Research on quality of life addresses the question of
how well patients are surviving. Key outcomes include patients’ self-reports of their health-related
quality of life and symptoms, as well as standardized
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Ayanian and Jacobsen
measures of functioning, such as performance tests of attention and
memory to assess cognitive functioning. Consistent with the aim of
improving the quality of life of cancer survivors and with recent
reports on cancer survivorship from the Institute of Medicine1 and the
President’s Cancer Panel,2 the following topics are priorities for research: identifying common and important quality-of-life problems
faced by survivors; identifying mechanisms and risk factors underlying these problems; and developing and evaluating strategies to prevent and treat these problems.
IDENTIFYING IMPORTANT QUALITY-OF-LIFE ISSUES
Identifying common and important quality-of-life issues faced by
survivors can inform larger efforts to direct resources to yield the
greatest benefits. From a practical perspective, it makes sense to focus
efforts on problems that affect the greatest number of survivors. This
consideration must be balanced against the relative importance of the
problems. Addressing a problem or symptom that is relatively uncommon but has a profoundly negative impact on quality of life among
survivors may be just as valuable as addressing a problem or symptom
that has only a moderately negative impact on quality of life, but is
common among survivors.
Data currently available to inform these decisions consist primarily of surveys of patients with single diseases at single institutions.3 To
ensure greater generalizability of the findings, it will be important to
conduct research that includes population-based sampling or large
cohorts of survivors assembled from multiple treatment settings. Examples of such efforts include a population-based survey of quality of
life among men with prostate cancer,4 a registry-based survey of the
long-term quality of life among hematopoietic stem-cell transplant
recipients seen at 40 different treatment centers,5 and the Cancer Care
Outcomes Research and Surveillance Consortium that is studying
patients with colorectal cancer or lung cancer from multiple regions
and health care systems in the United States.6
IDENTIFYING MECHANISMS AND RISK FACTORS FOR
IMPAIRED QUALITY OF LIFE
As common and important quality-of-life issues are identified, research then needs to focus on identifying the mechanisms and risk
factors underlying these issues. Elucidating mechanisms is critical,
thereby allowing empirical evidence to guide the development of
interventions. When coupled with identifying risk factors, strategies
can be developed to ameliorate problems in their early stages or even
prevent them from developing. To date, efforts to identify risk factors
have focused primarily on demographic and treatment variables. This
line of research has shown, for example, that female sex predicts
greater psychological distress among cancer patients.7 In moving forward, the field will be better served by considering a broader range of
risk factors. One way to broaden the search is to evaluate modifiable
risk factors—these factors can serve as targets for prevention efforts. A
growing body of evidence suggests, for example, that avoidant forms
of coping during treatment are a risk factor for post-treatment distress,8 and these approaches to coping may represent a modifiable risk
factor. A second way to broaden the search is to consider biologic
factors that may confer high-risk status. Preliminary research suggests
that cancer patients who possess the ⑀4 allele of the APOE gene are at
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greater risk for post-treatment cognitive problems,9 and this finding
may represent a promising example of a biologic risk factor with
clinical relevance to improving quality of life.
DEVELOPING AND EVALUATING PREVENTION AND
TREATMENT STRATEGIES
Systematic reviews and meta-analyses of randomized clinical trials
have identified a number of interventions that effectively address
quality-of-life issues faced by cancer survivors.10-12 Although some
interventions have been effective, their impact on clinical care has
been limited due to two common features of this research.
First, much of the research has not included eligibility criteria
with regard to the severity and sometimes even the presence of a
targeted problem.13 This approach is inconsistent with the delivery of
clinical care, which typically focuses on intervention with patients who
present with problems of moderate to high severity. Much of the
research on treatment of psychological distress in cancer patients, for
example, has been based on cohorts in which the average level of
distress was mild.10 A more promising strategy would be to demonstrate the effectiveness of interventions with patients who are experiencing problems of moderate to severe intensity, a group more typical
of those for whom the interventions will be used clinically. Once
efficacy has been demonstrated in this context, research would logically proceed to testing interventions to prevent problems from occurring or progressing to greater severity.
A second factor limiting clinical applicability is that many interventions studied in randomized clinical trials require commitments of
patient and professional time so considerable that they may be difficult
to disseminate even if found to be efficacious.13 Designing and evaluating interventions with regard to how well they can be disseminated is
one means of improving the translation of research into practice.14
IMPROVING QUALITY OF CARE FOR CANCER SURVIVORS
A second major priority for new research is to improve the quality of
care for cancer survivors. Because of the multifaceted nature of cancer
treatment and surveillance involving numerous physicians for most
patients, cancer survivors’ perceptions of the overall quality of their
care are strongly associated with their views about the coordination of
their care.15 The Institute of Medicine has strongly recommended the
widespread adoption of explicit survivorship care plans to overcome
the fragmented care that cancer survivors often receive after they
complete their primary course of cancer treatment.1 The President’s
Cancer Panel similarly has recommended that patients receive a treatment summary form when they complete their primary cancer treatment, as well as a survivorship care plan based on this treatment
summary.2 These treatment summaries and comprehensive written
survivorship care plans would be developed for each patient by an
oncology provider who coordinated his or her care. In addition to
summarizing the clinical details of a patient’s primary cancer treatment, the care plan would provide recommendations for follow-up
care, surveillance testing, potential preventive measures, and psychosocial support services.
Research on survivorship care plans could play a major role in
defining how these patient-specific plans are developed, implemented, and refined. In either randomized or observational studies,
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Enhancing Research on Cancer Survivors
patients who received survivorship care plans could be compared with
patients receiving usual care without these plans regarding their satisfaction with care, coordination of care, and communication with
health care providers about symptoms, surveillance testing, and psychosocial concerns. In the decentralized US health care system, the
primary goal of written survivorship care plans would be to improve
communication and coordination of care among patients, cancer
specialists, and primary-care physicians.
Another focus for improving the quality of care should be to
assess the value of current and proposed surveillance tests. The goal of
this research is to provide better evidence about whether surveillance
tests improve patients’ outcomes by identifying early cancer recurrences or second primary cancers while they can be alleviated or
cured.16 Research on survivorship care provided by cancer specialists
and primary-care physicians should then be conducted to assess adherence to evidence-based guidelines regarding surveillance testing. To optimize the allocation of health care resources, quality-of-care research can
evaluate underuse of appropriate tests, such as annual mammography
for breast cancer survivors or colonoscopy for colorectal cancer
survivors,17-19 as well as overuse of inappropriate tests such routine chest
radiographs or bone scans in asymptomatic breast cancer survivors.20
In addition to conducting better research on surveillance tests,
studies are needed to assess how survivorship care is delivered by
primary-care physicians, oncologists, or collaborative care that is
shared by these two groups. Randomized studies in the United Kingdom and Canada have found that breast cancer survivors received
effective survivorship care from primary-care physicians who were
well informed about cancer survivors’ symptoms and needs as defined
by evidence-based guidelines.21-25 In recent observational research in
the United States, elderly breast cancer survivors were most likely to
receive appropriate surveillance mammography when observed by
cancer specialists17 or by both cancer specialists and generalist physicians.19 Among elderly cancer survivors with other noncancer conditions such as congestive heart failure or diabetes, necessary services not
related to cancer were most likely provided when patients were observed by both primary-care physicians and medical oncologists, least
likely provided when observed by only oncologists, and intermediate
in likelihood when observed by only primary-care physicians.17,26
Finally, better evidence is needed to define performance measures that can be used to monitor and improve the quality of cancer
survivors’ care. Most current efforts to define and test performance
measures are focused on the initial treatment of newly diagnosed
patients with cancer, such as the Quality Oncology Practice Initiative
of the American Society of Clinical Oncology.27 Performance indicators related to survivorship care could include technical measures,
such as the use of surveillance tests for cancer recurrence and
standardized assessment tools for important symptoms and late
effects of treatment, as well as interpersonal measures related to
coordination of care and psychosocial support. Public and private
organizations that can help to promote the implementation of such
performance measures include the federal Center for Medicare and
Medicaid Services, American Society of Clinical Oncology, National Quality Forum (www.qualityforum.org), and National
Committee for Quality Assurance (www.ncqa.org).
EXPANDING OPPORTUNITIES FOR SURVIVORSHIP RESEARCH
The Institute of Medicine has identified four major approaches to
expand cancer survivorship research. First, greater follow-up of par-
ticipants is needed in randomized clinical trials with a focus on healthrelated quality of life and survivorship care. Second, greater follow-up
of participants is needed in large observational cohort studies. Third,
population-based cancer registries should have an increased role.
Fourth, greater focus should be placed on cancer survivors in federal
health surveys.
Patients in clinical trials represent an underused resource for
assessing the long-term effects of cancer and its treatments on quality
of life, and assessing ways that survivorship care can be improved.
These patients have demonstrated their willingness to participate in
research on the acute treatments for cancer, and many of them would
be willing to participate in subsequent survivorship studies if such
opportunities were offered to them. Incorporating long-term assessments of quality of life into randomized clinical trials of chemotherapeutic agents, for example, would make it possible to determine
whether differences in quality of life evident between treatment arms
during active treatment are sustained after treatment is completed. A
specific challenge is to convince sponsors and investigators of clinical
trials to build long-term follow-up assessments of quality of life into
the design of their studies. Essential elements of such studies include
prospective data collection on health-related quality of life at enrollment and at appropriate intervals after treatment is completed; additional resources are required to maintain contact with cancer
survivors and analyze more comprehensive data beyond overall survival and disease-free survival.
In addition to longer-term follow-up of participants in clinical
trials, survivorship research should be expanded in large observational cohort studies. The Childhood Cancer Survivor Study is a
well-established model for such research, enrolling more than
14,000 participants who have survived at least 5 years after treatment for a childhood cancer.28 Through the Cancer Care Outcomes Research and Surveillance Consortium and the Cancer
Research Network, the National Cancer Institute has already made
substantial investments in assembling research cohorts of adults
with newly diagnosed cancer identified from population-based
registries and large health care systems.6,29 The infrastructure developed for these projects provides promising platforms for expanded research on cancer survivors.
Cancer registries represent another mechanism for new research on large, representative cohorts of cancer survivors. Since
1973, the National Cancer Institute has funded the Survival, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) to monitor cancer incidence, staging, primary treatment
(within 4 months of diagnosis), and overall survival in multiple
regions representing more than one fourth of the U.S. population.
During the last decade, the National Program of Cancer Registries
(NPCR) funded by the Centers for Disease Control and Prevention
(www.cdc.gov/cancer/npcr) has supported substantial improvements in data collection at 45 state cancer registries. In addition,
the National Cancer Data Base sponsored by the American College
of Surgeons Commission on Cancer (www.facs.org/cancer/ncdb/
index.html) has collected data on about three fourths of newly
diagnosed patients in the United States through voluntary participation of hospital-based registries.
The registry data systems that comprise SEER, NPCR, and National Cancer Data Base provide a framework that could be used more
actively for identifying and contacting cancer survivors to participate
in research studies related to their quality of life and quality of care.
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Each of these major data resources could play a substantially greater
role in cancer survivorship research if participating registries were
funded to collect data on cancer recurrences from cancer providers
or through linkages with Medicare claims or electronic records of
health care delivery systems. The SEER database has been linked to
Medicare claims for patients diagnosed through 2002 (www.healthservices.cancer.gov/seermedicare), providing another source of data on
surveillance tests and cancer recurrences.
The fourth approach to expanding research on cancer survivors
would be to collect more detailed data on cancer survivors in federal
surveys. The National Health Interview Survey has included periodic
supplements devoted to cancer control in 1987, 1992, 2000, and 2005.
These supplements have provided useful information on cancer survivors in the general population,30-34 and with increased funding they
could be conducted more frequently and in greater depth to assess the
quality of life and health care experiences of cancer survivors. Similarly, the Medical Expenditure Panel Survey, which is the main federal
survey on the costs and uses of health care, could sample cancer
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Enhancing Research on Cancer Survivors
Authors’ Disclosures of Potential Conflicts of Interest
The authors indicated no potential conflicts of interest.
Author Contributions
Conception and design: John Z. Ayanian, Paul B. Jacobsen
Manuscript writing: John Z. Ayanian, Paul B. Jacobsen
Final approval of manuscript: John Z. Ayanian, Paul B. Jacobsen
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