European-American Dialogues on Cancer Survivorship: Current Perspectives and Emerging Issues
Cancer survivorship research in Europe and the United States: Where have we been, where are we going, and what can we learn from each other?
Version of Record online: 20 MAY 2013
Copyright © 2013 American Cancer Society
Supplement: European-American Dialogues on Cancer Survivorship: Current Perspectives and Emerging Issues
Volume 119, Issue Supplement S11, pages 2094–2108, 1 June 2013
How to Cite
Rowland, J. H., Kent, E. E., Forsythe, L. P., Loge, J. H., Hjorth, L., Glaser, A., Mattioli, V. and Fosså, S. D. (2013), Cancer survivorship research in Europe and the United States: Where have we been, where are we going, and what can we learn from each other?. Cancer, 119: 2094–2108. doi: 10.1002/cncr.28060
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health or the Patient-Centered Outcomes Research Institute.
European-American Dialogues on Cancer Survivorship: Current Perspectives and Emerging Issues
This supplement was guest edited by Vittorio Mattioli, MD (NCRC, Bari, Italy) and Kevin Stein, PhD (American Cancer Society, Atlanta, Georgia) and was produced with the authoritative contribution of 58 authors from the European Union and the United States. The primary aims are to highlight the potential differences between European and American approaches to cancer survivors' issues, increase coordination among oncologists and other primary care providers, and aid the development of a shared care model that can improve the quality of cancer care.
The opinions or views expressed in this supplement are those of the authors and do not necessarily reflect the opinions or recommendations of the journal editors, the American Cancer Society, John Wiley & Sons, Inc., or the National Cancer Research Centre Istituto “Tumori Giovanni Paolo II” Bari.
- Issue online: 20 MAY 2013
- Version of Record online: 20 MAY 2013
- Manuscript Revised: 16 JAN 2013
- Manuscript Accepted: 16 JAN 2013
- Manuscript Received: 27 JUL 2012
- United States
The growing number of cancer survivors worldwide has led to of the emergence of diverse survivorship movements in the United States and Europe. Understanding the evolution of cancer survivorship within the context of different political and health care systems is important for identifying the future steps that need to be taken and collaborations needed to promote research among and enhance the care of those living after cancer. The authors first review the history of survivorship internationally and important related events in both the United States and Europe. Lessons learned from survivorship research are then broadly discussed, followed by examination of the infrastructure needed to sustain and advance this work, including platforms for research, assessment tools, and vehicles for the dissemination of findings. Future perspectives concern the identification of collaborative opportunities for investigators in Europe and the United States to accelerate the pace of survivorship science going forward. Cancer 2013;119(11 suppl):2094-108. © 2013 American Cancer Society.
The dawning of the new millennium ushered in a new era for cancer control globally, one heralded by the rise of interest in the health, functioning, and psychosocial well-being of those living through and beyond a cancer diagnosis. The “cancer survivorship” movement started in the United States and is increasingly being championed in diverse countries across Europe. However, to date, survivorship research has occurred in a fragmented fashion with the need for international ventures only now being recognized. In this article, we: 1) review and compare the evolution of the field of cancer survivorship research in the United States and in Europe, with illustrative examples; 2) discuss the knowledge generated from this work and the new directions this science is taking; and 3) identify resources needed to advance this science. We also highlight areas where future international collaborations will serve to accelerate the pace of translation from research findings to improvements in care of the growing population of cancer survivors.
Evolution of a Field
Forty years ago, the survival rates for all cancers combined were low.[1, 2] Relatively few effective treatment options were available; of those that were, many had serious side effects. Because of advances in recent decades in early detection, effective therapies, and supportive care, 5-year survival rates have increased to 50% or more in adults with a history of cancer in the United States and in many European countries, and there are growing numbers of people living with and beyond a diagnosis of cancer.[4, 5] In the United States and Europe, the greatest improvements in survival were seen for childhood cancers and malignancies of young adults (eg, Hodgkin's lymphoma, testicular cancer).
These advances have led us to begin to ask important questions: What are the persistent problems and late effects in individuals who have survived their cancer? Which survivors are at particular risk for developing late effects? What is the impact of a history of cancer on individuals' careers, families, and wider society? How can late and long-term effects be cost-effectively prevented, detected, and managed?
Evolution of Survivorship Science in the United States
Progress made in cancer prevention and control in the United States is often dated from the signing of the National Cancer Act on December 23, 1971 (Fig. 1). However, the launch of the survivorship movement in the United States is generally linked to 2 events: a 1985 publication in the New England Journal of Medicine by a young physician, Dr. Fitzhugh Mullan, describing his journey with cancer, which he labeled as the “Seasons of Survival,” and the creation a year later of the National Coalition for Cancer Survivorship (NCCS). At the first meeting of the NCCS in October 1986 in Albuquerque, New Mexico, Mullan and the two dozen founding members proposed a new definition for “cancer survivor.” Up to that time, the term “cancer survivor” was deemed by the medical community to refer to someone who had remained disease-free for a minimum of 5 years. NCCS members reasoned that cancer patients could not wait 5 years to make decisions about outcomes that would be affected by specific treatment choices (eg, fertility preservation, receiving a drug that could alter lung capacity or risk for peripheral neuropathy). They proposed that a person should be considered a survivor from the time of diagnosis onward. The revised definition was designed to provide hope and, importantly, to change the medical dialogue such that cancer treatment decisions would be made predicated on a patient's preferences and desires regarding life after cancer. Although many treated for cancer do not refer to or think of themselves as survivors, this language has taken hold broadly in the United States. It also launched a cascade of activities promoting attention to the unique needs of cancer survivors.
One of the most compelling rationales for cancer survivorship research, namely, the sheer growth in numbers of those living through and beyond cancer in the United States, has been documented by the Surveillance, Epidemiology, and End Results (SEER) cancer registries (Fig. 2). The SEER registries, which were established by the National Cancer Act and currently cover approximately 28% of the US population (http://seer.cancer.gov/about/factsheets/SEER_brochure.pdf), provide a unique resource for quantifying the growing prevalent population of cancer survivors because they track survival through the balance of life for all cases reported. As of 2012, there were an estimated 13.7 million cancer survivors in the United States alone, representing approximately 4% of the population.
Several other key achievements in policy and research support have contributed to the growth of the field of cancer survivorship in the United States. The Office of Cancer Survivorship (OCS) at the National Cancer Institute (NCI) was established in 1996 to champion and direct research to identify and address the challenges faced by those living long-term after cancer. The American Cancer Society (ACS), established in 1913, funds research in cancer survivorship, and made a major commitment in 2000 to support survivorship science with the initiation of the Study of Cancer Survivors, a large population-based longitudinal study of quality of life. Part of the mission statement of the ACS is to diminish suffering from cancer.
In addition, the President's Cancer Panel, also established by the National Cancer Act, was tasked with monitoring the progress of the National Cancer Plan. The steady increase in the number of survivors and the lack of information about their health status and needs became the topic of the annual report of the President's Cancer Panel in 2003 to 2004. This report, and 4 additional national reports on the challenges to understanding and addressing the care of pediatric and adult cancer survivors,[14-16] brought national visibility to cancer survivorship research. These reports state that cancer survivorship needs to be addressed as a unique place on the cancer control continuum.
Attention to cancer survivors' health and needs in the United States has further benefited from a rich history of patient advocacy and public visibility around cancer. The informed consent movement in the late 1960s promoted attention to the rights of patients regarding information about the nature of their illness, and also their role in treatment decision-making. To be truly “informed,” a patient needs to understand the consequences of choices in care. Since the late 1970s, a number of high-profile figures have acknowledged their status as cancer survivors (eg, Betty Ford, wife of President Ford in 1976, and Lance Armstrong, whose visibility and foundation have had worldwide impact). These disclosures, along with a growing advocacy movement, helped lower cancer-related stigma in the United States and prompted a level of public dialogue about this disease. One measure of the impact these conversations have had is that when someone dies of cancer in the United States today, obituaries in major city newspapers now cite the cause of death as such, often indicating the specific type of cancer, instead of using the euphemism “died of a lingering illness.” In the absence of these types of public disclosures and dialogues, cancer still continues to be stigmatized in other countries around the world.
The growing visibility of cancer survivors in the United States also led to the creation of a number of organizations championing the research and care of specific populations of cancer survivors, with breast cancer advocates leading the way in the early 1990s, but who were quickly followed by organizations for diversity of cancer sites such as leukemia, colorectal cancer, prostate cancer, bladder cancer, pancreatic cancer, and so forth. Consumer advocacy was a driver behind the creation of the OCS at the NCI; it has also, at least in the past, functioned to increase federal spending on cancer.
There is wide variability in health care receipt and coverage by region, state, and health insurance type in the United States. Across the United States, cancer treatment and posttreatment follow-up care are poorly coordinated across multiple providers, settings, and payers. In particular, posttreatment cancer care lacks clear delineation of responsibility among providers, guidance for appropriate tests and treatments, and adequate reimbursement for all aspects of comprehensive care. This is true even for older adult survivors (aged 65 years and older) who are eligible for federally run Medicare health care coverage and programs. As a result, there was an initial dearth of attention paid to the needs of posttreatment cancer survivors. The well-documented limitations of the US health care system present challenges moving forward not only for understanding the multilevel problems experienced by those surviving cancer, but also for systematic implementation of clinical practice changes based on emerging research findings.
Another challenge to understanding and advancing health after cancer in the United States relates to limitations around cancer control plans. Individual state cancer plans, supported by the Centers for Disease Control and Prevention (CDC), have been in place since 1998. However, the inclusion of goals addressing cancer survivorship issues only occurred in the past decade, and only about a third of state plans in 2009 included survivorship sections or chapters (Irene Prabhu Das, NCI, personal communication, April 30, 2012). Furthermore, recommendations in cancer control plans related to survivorship are often unfunded or underfunded mandates addressed only to the extent annual state level budgets permit. Thus, although the United States has in the past decade seen a rapid increase in the attention to cancer survivors and survivorship research and practice, the ability to act on this knowledge is at times stymied by the lack of a uniform delivery system within which to test and implement changes designed to enhance the quality of life and length of survival of all of those diagnosed with cancer.
Evolution of Survivorship Science in Europe
Europe is a complex grouping of 50 countries (including Kazakhstan, in addition to the 49 listed here: http://europa.eu/about-eu/countries/index_en.htm) with more than 700 million inhabitants; marked cultural, economic, and societal variations; and significant variation in the models and levels of health and social welfare provision. Not surprisingly, the field of cancer survivorship research has followed a somewhat different trajectory in Europe. In contrast to the United States, in Europe, the term “cancer survivor” is used less often by individuals with a cancer diagnosis.[19, 20] In the European medical literature, this term is typically applied to cancer patients surviving tumor-free at least 5 years after their diagnosis, as described in the President's Cancer Panel Report Living Beyond Cancer: a European Dialogue. This distinction is reflected in the focus on late and long-term effects in European survivorship studies.
National cancer registries have existed in the Nordic countries for 60 to 70 years (since 1943 in Denmark, since 1951 in Norway, since 1952 in Finland, since 1955 in Iceland, and since 1958 in Sweden) and the Netherlands for more than 20 years (Fig. 1). In other countries (for example, Germany and the United Kingdom) regional cancer registries provide epidemiological data on cancer incidence and mortality. The establishment of both the International Agency for Research on Cancer (IARC) in 1965 and of the EUROpean CAncer REgistry (EUROCARE) in 1989 represented 2 important steps to generate pan-European data on cancer incidence, mortality, and 5-year prevalence (ie, those surviving at least 5 years after cancer diagnosis). However, the level of national coverage by such regional registries varies widely. In 2002, the prevalence of cancer survivors was estimated by a statistical model to be 2% of the total population in Europe, which represents an increase from 1% in the figures published for 1990 by IARC.
Although Europe lacks organizations specifically devoted to cancer survivorship comparable to those which have evolved in the United States, certain pan-European organizations representing different segments of cancer care have promoted the field of survivorship science; of note, many of these were established during the last decade (Fig. 1). Among these are the European Cancer Patient Coalition which represents the interests of all cancer patient groups, and the European Cancer League, an umbrella organization representing the majority of the national cancer organizations in Europe. A major policy achievement in Europe was the publication of “Communication on Action Against Cancer: European Partnership” in 2009, which highlighted several areas for improvement of cancer care in Europe, including a need for stronger collaboration within the European Union (EU) in cancer survivorship. Specifically, the report emphasized the need for identification and dissemination of evidence based practices to reduce the inequalities across the continent. Provision of comparable data on incidence, mortality and prevalence was mentioned explicitly. The European Commission also launched in 2009 The European Partnership for Action Against Cancer (EPAAC) with the aim, under a common platform, to unify cancer burden indicators (incidence, mortality, survival, and prevalence) provided by existing European data collection activities. The Commission also urged all member states to publish a cancer care plan by the end of 2013. National cancer plans have subsequently been published by 24 of 27 EU member states at the time of this publication (www.epaac.eu/national-cancer-plans). Most of these care plans deal with prevention, diagnosis, and treatment of cancer. The topic of cancer survivorship appears in approximately half of these plans, under sections referring to survivorship, rehabilitation, supportive and palliative care (beyond end-of-life care), and after-care.
In most European countries, treatment for cancer is free of charge for the individual patient, but the availability of novel drugs and application of new technologic advances differs. There are also considerable variations among countries regarding the structure of follow-up care for cancer patients after they have discontinued their cancer treatment. Follow-up care generally falls under the responsibility of medical specialists or family physicians, who often have limited knowledge of long-term follow-up and late complications, which renders systematic medical surveillance of long-term effects difficult.
Looked upon broadly, the concept of cancer survivorship does not seem to have had either a broad or uniform impact on the philosophy or aims of various stakeholders in European contemporary oncology and policy. The one exception to this has been in England, which formally launched a National Cancer Survivorship Initiative in September 2008. This latter is currently poised not only to transform medical care for those after treatment for cancer, but also to test models for the most effective and cost-efficient way to provide this care. Across other parts of Europe, some relevant efforts for survivorship research and care, such as providing reliable prevalence data or providing information of after-care such as rehabilitation, are noticeable nevertheless. During the last 5 years, both ESMO (European Society for Medical Oncology) and ESTRO (European Society for Therapeutic Radiology and Oncology) have included within their annual conferences organized sessions devoted to cancer survivorship. During the ECCO (European CanCer Organization)-ESMO conference in September 2011, medical specialists and representatives from European cancer advocacies, outlined cancer survivors' needs, including the need for attention to their continued participation in the work force. To the best of our knowledge, the first European conference solely addressing cancer survivorship (European Symposium on Late Complications after Childhood Cancer [ESLCCC]) was held in 2007 and now occurs in alternate years. These efforts notwithstanding, the large and increasing number of European cancer survivors and their expected national health burden in the years to come are not sufficiently reflected in the present aims of European efforts to improve cancer care.
Cancer survivorship research in Europe has so far largely been restricted to specified malignancies (childhood cancer, breast cancer, testicular cancer, Hodgkin's lymphoma) and conducted by a subset of medical specialists (mostly oncologists and pediatricians) and epidemiologists using existing databases and surveys.[26, 27] Most of these efforts have depended on time-limited grants. With a few exceptions, research and activities within the field of cancer survivorship have been hampered by the limited involvement of politicians and health care administrators on the national and the European levels. In the last 2 years, ESMO, the EORTC (European Organization for Research and Treatment of Cancer), and SIOPE (European Society of Pediatric Oncology) presented key issues in cancer survivorship to the European Parliament with the aim to attract European politicians' attention. So far, it seems that research and care in cancer survivorship has not attracted the attention of European health care researchers and decision-makers.
A principal challenge to survivorship research in Europe is the limited access to funding, both in terms of financial support and time restrictions. Some improvement has been observed during recent years in some countries, including the establishment of academic positions within the fields of cancer survivorship (eg, in Denmark, Norway, the Netherlands, and the United Kingdom) and government financial support of voluntary organizations' survivorship projects. A 5-year EU grant, funded by the 7th Framework Program of the European Commission and awarded in 2010 to the PanCare Childhood and Adolescent Cancer Survivor Care and Follow-up Studies (PanCareSurFup) project, indicates an awakening understanding of the importance of cancer survivorship research. A consortium of 16 institutions, PanCareSurFup will carry out research studies into the late effects of treatment for cancer, identify a virtual cohort of childhood cancer survivors for future studies, establish guidelines for follow-up, disseminate the results, and provide training and workshops for stakeholders. The overall goal of this project is to give health care providers the information they need to improve the long-term health of every European childhood cancer survivor.
In an effort to illustrate differences within Europe that affect cancer survivorship interest, we have summarized the nature of the cancer registry, care delivery, and in-country governmental activities for 3 countries familiar to the authors: Norway, the United Kingdom, and Italy (Table 1). Although all 3 of these nations have strong registry systems and national health programs, there is considerable variability in national attention to cancer survivorship. Whereas Norway has for a number of years drawn attention to the need for long-term follow-up for some cancer survivors (the current national guidelines for breast, prostate, and testicular cancer and Hodgkin's lymphoma contain recommendations for long-term follow-up), England's National Cancer Survivor Initiative is a relatively new but unique and comprehensive effort to advance survivorship research and care nationwide. Both Norway (National Resource Center for Studies after Treatment of Cancer Center, established in 2005) and Italy (National Multisite Research Program on Cancer Survivors, launched in 2008) invested in research infrastructures to study cancer survivors.
|Cancer Statistics||Health Care System||Key Achievements in Policy and Research Support|
|United Kingdom||• Population-based cancer statistics are available through 11 cancer registries, each covering populations of between approximately 1.65 million and 13.8 million people (http://www.ukacr.org/registration-organisation)|| |
• Health care is largely provided free of charge by the welfare state, through the National Health Service (NHS), at the time and point of need
• Cancer follow-up care occurs in hospital, community, or primary care settings. The duration and intensity of hospital follow-up has been inconsistent and variable and not always robustly evidence-based
• The Government's Cancer Reform Strategy identified key priorities, including the need for a greater focus on survivorship (2007)
• The National Cancer Survivor Initiative (2010) was established to enhance cancer survivor care, and promote epidemiologic health services research in cancer survivorship
• Improving Outcomes: A Strategy for Cancer (http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_123394.pdf) highlighted the national commitment to enhancing care for survivors (2011)
• The Department of Health committed significant recourses to cancer data collection through the National Cancer Intelligence Network (2011) and the National Patient Reported Outcome Programme (2012–2015)
• National registry with 100% coverage provides cancer incidence, mortality and prevalence in the population (5 million)
• Survivors can be linked to other databases (eg, the National Birth registry) through a unique personal identification number
• Cancer treatment and follow-up are free after the patient has paid annual expenses comparable to $625
• Cancer follow-up is viewed as a shared responsibility between specialists and family doctors, with care shifting more to family doctors as years elapse since treatment
• The National Cancer Plan (NCP) identified palliation (1997) and awareness of late effects after and rehabilitation after cancer treatment (2004)
• The National Resource for Studies after Treatment of Cancer established to promote research, training, and knowledge dissemination (2005)
• The Directorate of Health expert group (2010) outlined physical and psychosocial needs of cancer survivors and proposed solutions to meet these needs
• 29 cancer registries (ICR) that cover <50% of Italy's population report incidence, mortality and survival
• There are also 3 diagnosis-specific registries and 2 regional childhood registries
|• Cancer treatment and follow-up is free and includes necessary long-term follow-up|| |
• The Italian National Cancer Plan (2010–2013) aims to improve cancer follow-up and improve compliance with cancer registries
• National Multisite Research Program on Cancer Survivors funded to investigate the physical, psychological, and social sequelae of adult long-term cancer survivors; to identify the potential actions to prevent cancer sequelae; and to develop a rehabilitation plan to meet Italian cancers survivors' needs
Comparison of the Evolution of Survivorship Research in the United States and Europe
The number of publications dealing with cancer survivorship research has grown dramatically in both the United States and Europe (Fig. 3). The emerging interest in long-term cancer survivors has paralleled their growing numbers on both sides of the Atlantic.[1, 29] Survivorship science has become more sophisticated over time. Studies conducted in the 1970s and early 1980s focused on trends in overall survival and development of second malignancies. Subsequently, research into the broader aspects of cancer survivorship was greatly stimulated in both the United States and Europe by the dramatic progress in treating pediatric cancers and resulting concerns about the long-term consequences of cancer treatments (for example, Rowland et al). Later studies in the 2000s focused on the incidence and prevalence of persistent and late-onset adverse effects, including psychosocial problems,[31, 32] and interventions to treat these. More recent studies published since 2010 examine the markers and mechanisms of risk for poor outcomes and the cost-effectiveness of current health care provision for reducing preventable morbidity and mortality among long-term survivors.[34-36] Challenges encountered on both sides of the Atlantic in providing quality health care to a growing population of cancer survivors in the context of shrinking resources are a driving force behind current and emerging research. Furthermore, the lack of attention to and funding for recommendations related to survivorship in cancer control plans in both the United States and Europe needs to be addressed. Failure to attend to the major recommendations made by entities in the United States and Europe will result in an inability to appropriately support and care for the growing population of survivors globally.
Whereas the volume and pace of cancer survivorship research has accelerated rapidly in the past several years, this effect has been more pronounced in the United States than in Europe (Fig. 3). Three key reasons may account for this difference. First, the 5-year survival rates for several European nations are still < 50% (Fig. 4). In these countries, focusing research on enhancing survival rather than on survivorship outcomes is a reasonable priority, while recognizing, nevertheless, that quantity of life and quality of life are both valued survivorship outcomes. Although the overall 5-year relative cancer survival is higher in the United States than in several European countries, the United States demonstrates poorer overall health than most European nations according to most World Health Organization (WHO) indicators. Survivorship researchers and clinicians in Europe and the United States are keenly aware that increasing length of survival must be weighed thoughtfully against the human cost of such efforts.[38, 39] Second, historically, most European nations have not provided sufficient funding resources for long-term survivorship research. In contrast, the United States has benefited from strong congressional support for government-lead investment in cancer research, including survivorship science. The recent high profile of cancer survivorship in English national health policy and charity activities, with significant service improvement initiatives being centrally and locally commissioned, has not been mirrored by an equal investment in cancer survivorship research despite identification of the need for a systematic comprehensive research program. Finally, due to the greater stigma of cancer in some European countries relative to the United States, there has been less public discourse around, and hence more limited political attention paid to, cancer survivor issues in some European nations.
Lessons From Survivorship Research
A number of key lessons have been learned with considerable consistency on both sides of the Atlantic. First, most cancer survivors do well after treatment; they manifest remarkable resilience. However, it is also clear that there are few cancer therapies without any adverse effects. A second important finding is that cancer has the potential to affect every aspect of an individual's life: physical, psychological, social, economic, and existential or spiritual. Third, as survivors are followed for longer periods, the emergence of late effects (eg, second cancers, cardiac failure), sometimes years after discontinuation of cancer treatment, is often unexpected and has major impact on survivors' lives. Fourth, cancer survivors need risk-adapted follow-up care that reflects individual challenges, related to the type and treatment of their cancer and their specific other medical and psychosocial needs.[45, 46]
Taken as a whole, the research conducted in Europe and the United States highlights a number of gap areas in our knowledge base. It is unclear who may be at risk for what types of chronic or late-occurring effects of cancer and its treatment. Although some survivors experience few problems, others with similar disease and treatment may have many. More basic research is required to understand the mechanisms behind and the etiology of the observed long-term effects. Furthermore, limited interventions exist to address many of these effects (eg, chronic fatigue, sexual dysfunction, memory problems). Teasing apart what health problems may be secondary to cancer, exacerbated by the diagnosis and treatment, the result of underlying genetic predisposition, a function of environment or lifestyle, and/or simply an effect of aging remains a challenge. Because most survivorship research has included tumor-free and/or still young individuals, future studies have to deal with the problems of those living with some form of chronic treatment (eg, hormonal treatment in breast or prostate cancer) and elderly long-term cancer survivors. Finally, greater appreciation is also needed regarding what medical care should be delivered, by whom, when, and to which survivors. Future research should provide the evidence base for models of care for treating the growing population of cancer survivors, given a shrinking oncology workforce and including evidence for risk categorization. Furthermore, specific guidance is needed regarding surveillance for late and long-term effects and interventions to address future health status once cancer therapy ends.
Infrastructure for Survivorship Research
Platforms for Research
A vital barrier to studying survivors is access to this population as a whole and, importantly, detailed information on the treatments they may have received as part of their care. Some research documenting the long-term and late effects of cancer among survivors in both the United States and Europe is drawn from data from registries versus patient-contact studies; however, an increasing diversity of platforms (eg, surveys, epidemiological cohorts, and data linkages) is rapidly emerging within which to conduct survivorship research. Cancer registries are an important primary source for research on survival and persistent and long-term effects after cancer and were the basis for the earliest studies on second malignancies (www.epaac.eu/cancer-data-and-information). However, these registries historically do not contain reliable data on follow-up experiences. In particular, patient-reported outcomes (PROs), detailed treatment history (eg, specific chemotherapeutic agents and doses received), which can be important predictors of late effects, and comorbidities are not systematically collected in these registries. Registries can also be used as a sampling frame for recruitment to studies intended to contact survivors for further assessment, but registry-based recruitment presents challenges in terms of the delays for populating the registry with cancer cases, incomplete or inaccurate contact information for survivors, and nonresponse to recruitment and survey efforts. Despite this, progress is being made, and some registries have shown that PROs can be successfully linked to population-based registries (www.profilesregistry.nl). Moreover, whereas many registries have the capacity to capture second malignancies, few are capable of tracking recurrent or progressive disease. In certain countries, such as in Nordic countries, some of these shortcomings are overcome by linkages to other population-based registries, such as national birth registries or registries on education, income, sick leave, disability pensions, hospitalizations, and use of medications. The Nordic countries and the United Kingdom, with national health care systems and registries that serve almost 100% of cancer patients, have a unique advantage in conducting population-based survivorship studies because the health and resource utilization of their populations can be tracked. The use of a unique identification number for every citizen in Nordic countries enables researchers to approach cancer survivors even decades after a diagnosis to assess self-reported persisting or late-occurring effects of cancer and its treatment. Surveys among these individuals, especially when coupled with the collection of biological material and physical examination of survivors, can provide the opportunity to examine etiological mechanisms underlying the incidence of late effects among well-documented groups of survivors.[27, 34] There are 2 systems in the United Kingdom and the Netherlands in which patient-reported outcomes are integrated on a routine basis with cancer registry data: the ePOCS system and the PROFILES registry. The latter also disseminates cancer survivorship data free of charge for academic use (www.profilesregistry.nl). Across all registries, researchers must be aware of the variable quality of the data ascertained.
Access to these types of platforms is more limited in the United States where there are multiple health care delivery and payer systems and limited communication among these groups. The one exception is for survivors over the age of 65 years, the age at which US citizens can enter the government Medicare system. In recent years, linkages between the Medicare and the SEER cancer registry systems make it possible to examine health care utilization of the large population of older cancer survivors. However, complete records of cancer treatments are not available from SEER, and as noted earlier, SEER covers only 28% of the US population. This is a significant limitation for investigators who wish to identify treatment exposures that may be associated with specific types and severity of cancer-related symptoms or conditions. In addition, because there is usually limited information on the health status and behaviors of survivors prior to diagnosis, ascertaining what may be cancer-related effects versus problems or conditions with another etiology is difficult to assess. In an effort to address this challenge and to better understand the relationship between patterns of care and survivorship outcomes, the NCI created the Health Maintenance Organization Cancer Research Network (http://crn.cancer.gov/about/CRN_fact_sheet.pdf). A consortium of 14 health care delivery systems, covering almost 11 million US individuals, the Cancer Research Network has the potential to examine such questions as what the impact of different types of service use may have on survivors' health outcomes, how cancer in one member may affect health care status and utilization by other family members, and whether patient navigator programs can reduce illness-associated morbidity; these are questions some of their European counterparts are already able to answer for their own populations.
Other complementary platforms for survivorship research used by US investigators include national health surveys and data from large, prospective epidemiologic cohorts. Examples of these include the National Health Interview Survey (NHIS) an annual in-person, population-based survey of noninstitutionalized household members, and the Nurses' Health Study, a large, longitudinal cohort study of the health and well-being of these professionals over their life course.[56, 57] Although often lacking detailed cancer treatment information, these databases permit comparison of the health and functioning of survivors with that of their peers not affected by cancer.
An additional source of survivor populations used in both the United States and Europe include samples drawn from those entered into cancer clinical trials. In many cases, clinical trial cohorts have the unique advantage of permitting access to detailed treatment information, and data on therapies delivered under carefully controlled conditions. However, participation rates in clinical trials among adults in Europe (approximately 5% of the adult cancer population; Jon Bean, EORTC personal communication, April 26, 2012) and the United States (approximately 2% to 3% of the adult cancer population, although these numbers are much higher for pediatric cancer patients, most of whom are entered into one or more clinical trials) are low. It is important to note that for many of those diagnosed with cancer, there may be no available trial or they may be ineligible for study entry. The fact that the denominator commonly used to estimate trial participation includes all diagnosed individuals may account for the disturbingly low figures. Furthermore, due to stringent exclusion criteria, only the healthiest patients are entered into these studies, a practice that severely limits generalizability of findings to the broader population of survivors. Importantly, comorbid health conditions, more common among older survivors, often preclude trial inclusion, thus eliminating the opportunity to characterize those who may be most vulnerable to experiencing adverse survivorship outcomes. Finally, in addition to these challenges, one study details the barriers to recruiting cancer survivors retrospectively from clinical trials and reported a final participation rate of only 29%, due to difficulty locating patients, lack of institutional commitment, and lack of patient interest. Maintaining low rates of those who drop out or are lost to follow-up is critical in efforts to reliably identify those at risk for adverse effects. A number of retention strategies may be needed to ensure long-term participation.
The development and support of cancer survivor–specific cohorts for the purpose of advancing survivorship studies remain limited. Despite this, a number of these have been enormously productive including, but not limited to, the longitudinal follow-up of the childhood cancer cohort in the United States (Childhood Cancer Survivor Study, CCSS), the British Childhood Cancer Survivor Study (BCCSS), the American Cancer Society's Studies of Cancer Survivors cohort study, the Health, Eating, Activity and Lifestyle (HEAL) study of breast cancer survivors, the repeated examination of breast cancer survivors as done by the Early Breast Cancer Clinical Trial Group organized from Oxford (United Kingdom), and the European-American studies on long-term effects after testicular cancer.[27, 62]
A number of broadly used tools exist in Europe (eg, EORTC-QLQ-C30) and the United States (eg, FACT system) to evaluate the health-related quality of life of cancer survivors, in particular during active treatment. Fewer measures, however, are designed to capture survivors' outcomes after treatment, with exceptions such as the Impact of Cancer (IOC) scale. Two US efforts over the past several years show promise of helping to fill this gap, and potentially prove useful for international collaboration: the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Both of these NCI-sponsored data collection systems provide a data collection platform for measuring PROs with the purpose of investigating health outcomes. While PRO-CTCAE is currently being tested in the context of clinical trials, the measures are intended to be used for long-term follow-up to identify late-effects of therapy. The modular approach followed by both the EORTC Quality of Life group and the Functional Assessment of Cancer Therapy (FACT) system, in which patients complete a core health-related quality-of-life assessment tool in combination with disease-specific supplementary tools, may provide a useful basis for the development of survivorship-specific tools. Studies suggest that survivors report poorer physical and mental health than individuals without a history of cancer.[68, 69] A key lesson learned, as this science has evolved, is that a single summary score of quality of life may fail to reflect the diversity of chronic and late effects experienced by subsets of this population. The capacity to describe and compare across diverse countries and cultures these different illness-related outcomes will be important to advancing our knowledge about and ability to effectively care for cancer survivors globally.
Fortunately, as the field has grown, so too have outlets for dissemination of the findings of the emerging body of survivorship science. As noted earlier, a number of international groups now host survivorship content at their annual meetings. In 2002, the American Society of Clinical Oncology (ASCO) added a “Patient and Survivor” track to its annual proceedings. This track received increased visibility in 2005 under ASCO's then president, Dr. David Johnson, a cancer survivor himself. In collaboration with the ACS, and subsequently LIVESTRONG and the CDC, the NCI's OCS has hosted 6 Biennial Cancer Survivorship Research conferences. In 2007, the Journal of Cancer Survivorship was launched. A number of professional journals have issued special issues focused on cancer survivorship (eg, Journal of Clinical Oncology, Journal of Pediatric Psychology, The Cancer Journal) or contain separate sections on cancer survivorship in each volume (eg, Pediatric Blood and Cancer; Cancer Epidemiology, Biomarkers, and Prevention). Two textbooks addressing cancer survivorship have also appeared.[72, 73] Supporting the continued presentation and application of pertinent findings resulting from survivorship studies remains a pressing need. History has taught us that knowing about the problems survivors face is insufficient, but rather finding and disseminating evidence-based ways to address these must be an integral part of the science being conducted.
Research for cancer survivors, while no longer in its infancy, is being challenged to keep pace with global changes in demography, the economy, and patterns of cancer-related and non–cancer-related morbidity and mortality. The evolution of novel cancer therapies and the means to deliver these are also putting pressure on the scientific community to understand the acute and long-term effects of these innovations on survivors' health and function. It is clear that to meet these demands for knowledge in a timely fashion, efforts to identify the unique strengths of specific countries to answer given questions, and to foster cross-continental collaboration whenever advantageous, will be at a premium. For example, international collaborative efforts would facilitate increased power to study less common cancers or cancer-related events, answering similar research questions in multiple populations (eg, by cancer site, health care systems, and the like), greater generalizability of research findings, and more efficient use of otherwise disjointed research funds allotted to similar causes. The European Collaborative Group on Cancer Survivorship (ECGCS; www.ecgcs.eu), founded in April 2012 in Bari, Italy, hopes to do just this by bringing together European survivorship researchers and international advisors from the United States, Canada, and Australia in order to share knowledge more efficiently, reduce research fragmentation and overlap, and take advantage of larger, multinational cohorts.
Moving forward, models for research will benefit from using experiences in other related areas of health care. Although cancer may be episodic or cured for some, cancer has become or will be, for many, a chronic disease, making experiences from other fields within the health care system that deal with chronic disease increasingly relevant. In particular, the premium placed by these models on support of patient self-management of symptoms, on good patient–doctor communication, and long-term involvement in medical surveillance may be particularly helpful in structuring long-term survivorship care. Furthermore, systematic use of disability assessment may also be appropriate. For example, the International Classification of Functioning, Disability and Health (ICF) is WHO's framework for measuring health and disability at both individual and population levels. The ICF is officially endorsed by all 191 WHO Member States.
A number of collaborative opportunities exist to move this science forward in an efficient and effective manner. Specific areas for future development include:
- Promotion of international and collaborative research that examines mechanisms underlying development of late effects and their interindividual variability. This research should include genomic studies, which require large samples and warrant establishment of research collaboration, and should inform the development of targeted preventive and treatment programs.
- Performance of continuous surveillance to better understand the prevalence and trajectory of long-term and late effects, as well as yet-to-be-discovered late effects.
- Development of evidence-based models for risk-adapted long-term follow-up for different risk groups of survivors that consider survivor outcomes as well as cost-effectiveness and health care systems factors.
- Determining which countries have the best resources to answer specific research questions. For example, studies examining different models of care and associated outcomes/costs may be easier to conduct in Europe than in the United States, given varied health care systems across the European nations.
- Establishment or expansion of national cancer registries with valid exposure data (disease variables and cancer treatment). This must include finding solutions to the challenges associated with harmonizing data across countries/registries due to differences in care delivery, differences in populations covered by health care systems, and different structures of the registries.
- Routine linkage and inclusion of patient-reported outcomes data into regional and national cancer registries.[49, 52]
- Development of brief, standardized cancer-specific measures to assess patient-reported outcomes of health-related quality-of-life dimensions, symptoms, health behaviors, and comorbid conditions in cancer survivors.
- Coordination of efforts to stimulate the use of common data elements in clinical trials so that findings can be compared or combined.
- Establishment of international cohorts that can be followed and assessed at regular intervals during the patient's lifetime with the aim to examine the interaction between cancer survivorship, comorbidity, and aging.
- Application of new technologies to make convening key international players and development of new international collaborations more feasible.
- Fostering creation of unique international collaborations to share best practices in relation to policy development.
- Identification of effective communication strategies to make politicians and stake-holders aware of this rapidly growing area within health care, especially in Europe.
- Leveraging the voice of survivors/advocates to advance attention to and funding for research among and care of cancer survivors.
In this article, we review both the accomplishments and the lingering challenges in survivorship in the context of the growing number of cancer survivors worldwide. By providing details on the state of survivorship in both the United States and Europe, we highlight the need for and emergence of collaborative opportunities across borders. We further hope that this article will galvanize future research efforts, particularly in the realm of implementing interventions to improve the health and well-being of cancer survivors moving forward. Finally, we were tasked for this article with describing US/European activities around cancer survivorship research. A similar comparative exercise across additional regions, such as Asia, Australia, Africa, and Central and South America, may identify best practices and models to reduce cancer survivors' morbidity and mortality globally.
This supplement was sponsored by the National Cancer Research Centre Istituto Tumori “Giovanni Paolo II” Bari (Italy) through the Italian Ministry of Health-funded research project “Multidimensional assessment of long-term cancer survivors including discovery of genetic bases of susceptibility, depressive stage, prevention of affective disorders,” and through intramural funding of the American Cancer Society's Behavioral Research Center.
CONFLICT OF INTEREST DISCLOSURE
The authors made no disclosure.
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