The National Cancer Institute has determined that there are >10 million people alive today in the United States who have been diagnosed with cancer, and nearly two thirds have survived >5 years after their initial diagnosis (1). With the current advances in early detection and treatment, certain types of cancer that were once uniformly fatal, such as large majority of pediatric cancer, testicular cancer, and Hodgkin lymphoma, are now potentially curable. Additionally, patients with other common neoplasms, such as breast and colorectal cancers, enjoy improved disease-free and overall survival as a result of adjuvant therapy.

The number of cancer survivors in the United States has tripled since 1971 and is growing at the rate of 2% every year (2). It is therefore imperative to focus on the health and well-being of this large and ever-increasing population of cancer survivors. Cancer survivors represent a remarkably diverse group, characterized by a wide range of cancer diagnoses, clinical/biological features of their primary cancer, treatment exposures, social and demographic characteristics, and other comorbid health conditions. For example, whereas breast, prostate, and colorectal cancer account for >50% of all cancer survivors, >5 million survivors have been diagnosed and treated for other forms of cancer (Fig. 1). Furthermore, cancer is largely a disease of older persons, and thus, the majority of cancer survivors are older than 65 years (3). Thus, survivorship for the vast majority of cancer survivors occurs in a background setting of comorbid conditions, with a potentially greater effect on the health status of elderly cancer survivors (3).

Figure 1.

Estimated number of persons alive in the United States diagnosed with cancer by site (n = 10.5 million).

Figure 1.

Estimated number of persons alive in the United States diagnosed with cancer by site (n = 10.5 million).

Close modal

In recent years, research on quality of life in cancer survivors has increased steadily, consistent with the increasing recognition that end points other than disease-free survival are important to consider when evaluating the effectiveness of long-term survival (reviewed by Ayanian and Jacobsen; ref. 4). Contributing to this expansion of research has been the efforts of the National Cancer Institute Office of Cancer Survivorship. As summarized in Table 1, much of the increasing body of literature on treatment-related morbidities has come from research among childhood cancer survivors (5, 6). Thus, although research in childhood cancer survivors has conclusively shown that chronic health conditions are more prevalent, serious, and persistent in cancer survivors, when compared with age- and sex-matched siblings (7), the substantially larger population of survivors of adult-onset cancers remain understudied (8).

Table 1.

Summary of selected treatment-related adverse events in cancer survivors

ExposurePotential adverse events
Surgery  
    Surgery involving central nervous system Impaired cognition, motor and/or sensory neurologic sequelae 
    Head and neck surgery Difficulty swallowing, impaired speech, cosmetic, psychosocial morbidity 
    Lymph node dissection Lymphedema, retrograde ejaculation in testicular cancer 
    Abdominal surgery Intestinal obstruction, hernia 
    Pelvic surgery Sexual dysfunction, incontinence, hernia, intestinal obstruction 
    Splenectomy Impaired immune function—increased risk of sepsis 
    Amputation, Limb-sparing procedures Cosmetic, psychosocial morbidity, arthritis, phantom/neuropathic pain, functional impairment 
    Lung resection Impaired pulmonary functions, fatigue 
    Prostatectomy Urinary incontinence, sexual dysfunction 
    Oophorectomy Premature menopause, infertility 
    Orchiectomy Infertility, testosterone deficiency 
    Ostomy Bowel obstruction, nausea/constipation/anorexia, fatigue, poor body image 
Chemotherapy  
    Alkylating agents Therapy-related myelodysplasia/acute myeloid leukemia (t-MDS/AML), gonadal failure, premature menopause, infertility, bladder cancer, bladder fibrosis (hemorrhagic cystitis), congestive heart failure (high-dose cyclophosphamide) 
    Anthracyclines Cardiomyopathy, cardiac arrhythmias, t-MDS/AML 
    Bleomycin Pulmonary fibrosis 
    Platinum compounds Hearing loss, t-MDS/AML, impaired renal function, neuropathies 
    Corticosteroids Osteoporosis, avascular necrosis, cataracts 
    Trastuzumab Congestive heart failure 
    Taxanes Congestive heart failure, neuropathy 
    Carmustine Pulmonary fibrosis 
    Topoisomerase II inhibitors t-MDS/AML 
    Vinca alkaloids Neuropathy 
    Tamoxifen Hot flashes, stroke, uterine cancer, blood clots 
    Aromatase inhibitors Osteoporosis 
Radiation therapy  
    Site of radiation Second cancers 
    Bone and soft tissue Atrophy, cosmetic, fibrosis, avascular necrosis 
    Heart Coronary artery disease, congestive heart failure, pericarditis 
    Oral cavity Dental caries, xerostomia 
    Cranial radiation Hypopituitarism, neurocognitive dysfunction 
    Thyroid Hypothyroidism, thyroid cancer 
    Gonads Hypogonadism, infertility, premature menopause 
    Gastrointestinal tract Intestinal strictures, malabsorption 
    Lymph nodes Lymphedema 
    Eye Cataracts 
    Lung Interstitial pneumonitis, pulmonary fibrosis 
    Kidney Renal impairment 
ExposurePotential adverse events
Surgery  
    Surgery involving central nervous system Impaired cognition, motor and/or sensory neurologic sequelae 
    Head and neck surgery Difficulty swallowing, impaired speech, cosmetic, psychosocial morbidity 
    Lymph node dissection Lymphedema, retrograde ejaculation in testicular cancer 
    Abdominal surgery Intestinal obstruction, hernia 
    Pelvic surgery Sexual dysfunction, incontinence, hernia, intestinal obstruction 
    Splenectomy Impaired immune function—increased risk of sepsis 
    Amputation, Limb-sparing procedures Cosmetic, psychosocial morbidity, arthritis, phantom/neuropathic pain, functional impairment 
    Lung resection Impaired pulmonary functions, fatigue 
    Prostatectomy Urinary incontinence, sexual dysfunction 
    Oophorectomy Premature menopause, infertility 
    Orchiectomy Infertility, testosterone deficiency 
    Ostomy Bowel obstruction, nausea/constipation/anorexia, fatigue, poor body image 
Chemotherapy  
    Alkylating agents Therapy-related myelodysplasia/acute myeloid leukemia (t-MDS/AML), gonadal failure, premature menopause, infertility, bladder cancer, bladder fibrosis (hemorrhagic cystitis), congestive heart failure (high-dose cyclophosphamide) 
    Anthracyclines Cardiomyopathy, cardiac arrhythmias, t-MDS/AML 
    Bleomycin Pulmonary fibrosis 
    Platinum compounds Hearing loss, t-MDS/AML, impaired renal function, neuropathies 
    Corticosteroids Osteoporosis, avascular necrosis, cataracts 
    Trastuzumab Congestive heart failure 
    Taxanes Congestive heart failure, neuropathy 
    Carmustine Pulmonary fibrosis 
    Topoisomerase II inhibitors t-MDS/AML 
    Vinca alkaloids Neuropathy 
    Tamoxifen Hot flashes, stroke, uterine cancer, blood clots 
    Aromatase inhibitors Osteoporosis 
Radiation therapy  
    Site of radiation Second cancers 
    Bone and soft tissue Atrophy, cosmetic, fibrosis, avascular necrosis 
    Heart Coronary artery disease, congestive heart failure, pericarditis 
    Oral cavity Dental caries, xerostomia 
    Cranial radiation Hypopituitarism, neurocognitive dysfunction 
    Thyroid Hypothyroidism, thyroid cancer 
    Gonads Hypogonadism, infertility, premature menopause 
    Gastrointestinal tract Intestinal strictures, malabsorption 
    Lymph nodes Lymphedema 
    Eye Cataracts 
    Lung Interstitial pneumonitis, pulmonary fibrosis 
    Kidney Renal impairment 

Abbreviation: t-MDS-AML, therapy-related myelodysplasia/acute myeloid leukemia.

The vast majority of cancer outcomes described in the adult cancer survivors has depended upon registry data, clinical trials data, or has been drawn from small convenience samples. One of the more reliable sources of treatment-related events is the randomized trial because it allows for capture of protocol-specified therapeutic exposures. However, many individual trials conducted in the adult cooperative group setting are small, with very low participation rates and lack sufficient statistical power to detect the very rare or low incidence treatment-related events. For this reason, data on the frequency and severity of treatment-related adverse events in the adult cancer population often comes from registry studies. These studies are subject to various biases that may underestimate or overestimate the association between treatment exposure and adverse events. For example, a large dropout rate from follow-up may overestimate the true incidence of adverse event, whereas serious underreporting of the event of interest due to lack of follow-up by the participating sites may underestimate the true incidence. In addition, information on family history or underlying comorbidities, such as hypertension, diabetes, and smoking are not assessed in many of these studies, and therefore, the effect of these factors on the risk of treatment-related toxicity is unknown. Thus, some of the critical questions about cancer outcomes in the adult cancer populations will require research involving large patient populations—populations that are representative of the cancer survivor community, and have been followed for long periods of time, with a greater range of patients than is offered by adults treated on cooperative group clinical trials or at smaller cancer centers.

As previously noted, cancer survivors are a very heterogeneous population. The risk for adverse events usually depends on therapeutic exposures, when those treatments were delivered (because regimens and techniques change over time), the length of time that has elapsed since those exposures, and underlying risk factors independent of the primary cancer or its treatment. Moreover, cancer is largely a disease of the elderly, so determining late effects from unrelated comorbid conditions can be difficult. Outcomes research in cancer survivors therefore represents several challenges unique to this field. Additionally, the outcomes are relatively infrequent, requiring assembly of large, relatively uniform cohorts. The events occur after a latency of several years, sometimes decades, necessitating long and complete follow-up of these large populations. Finally, the study population needs to be well-characterized in terms of sociodemographic characteristics, detailed therapeutic exposures as well as comorbidities and family history. Having these data available when assessing long-term outcomes allows for adjustment for potential confounding and/or the ability to investigate the relationship between these variables and adverse events.

Survivorship research should be expanded to include large multidisciplinary initiatives consisting of observational cohort studies and programmatically aligned projects (e.g., program projects). The National Cancer Institute–funded (CA 55727) Childhood Cancer Survivor Study (CCSS) is a well-established model for such research, enrolling >14,000 participants who have survived at least 5 years after treatment for childhood cancer (9). Survival rates for many of the childhood and adolescent cancers improved at a remarkable pace beginning in the early 1970s. With this success came the need and responsibility to consider the long-term morbidity and mortality associated with the treatments responsible for the increases in survival. To varying degrees, it had been shown that long-term survivors were at risk of developing a spectrum of adverse outcomes including premature death, second neoplasms, organ dysfunction (e.g., cardiac, pulmonary, gonadal), reduced growth and development, decreased fertility, impaired cognitive function, difficulties obtaining employment and insurance, and overall reduction in quality of life. Because of the young age of these cancer survivors, and thus the potential longevity, the delayed consequences of therapy may have a greater effect on their lives, families, and on society at large, than the acute complications of the cytotoxic therapies they have already experienced. Although single-institution studies, some limited consortia, and, occasionally, cooperative clinical trials groups, pursued investigation of late sequelae, it became increasingly clear that there were limitations inherent in these approaches. Single institution investigations provided many of the initial observations on selected sequelae occurring at relatively high frequencies or associated with severe morbidity. However, many of these single institution investigations and limited consortia were restricted by a small sample size and were often derived from patient populations that were treated in a similar fashion. Thus, accurate quantification of a complete range of risk was often impossible. Some studies of long-term survivors had been carried out within established consortia or cooperative clinical trials groups but with varied success. The pediatric cooperative groups had a primary objective of conducting therapeutic clinical trials and, although questions of health-related outcomes were of interest, the resources did not always exist to provide the necessary support to successfully conduct such nontherapeutic studies. Thus, it was determined that there was a critical need for an infrastructure, such as CCSS, for late-effects research that would overcome these limitations and move the field forward.

The case can be made that the status of survivorship research among adult-onset cancers is not dissimilar to the situation of childhood cancer survivorship research at the time the CCSS was proposed. Thus, investment in large-scale, multidisciplinary research initiatives among survivors of adult-onset cancers should be made.

The CCSS represents an outstanding example of a retrospective cohort study established to capture data on childhood cancer survivors; such information has proven to be extremely valuable in establishing the true incidence of, and quantifying relative-risk for, a broad range of adverse events within childhood cancer survivors. The CCSS has been successful because of the size and diversity of the cohort, which is extremely well-characterized in terms of therapeutic exposures and because of the very high participation rates of the cohort members—with follow-ups extending into decades. Because of these characteristics, the CCSS has been able to answer a wide spectrum of questions (Table 2) and represents a unique resource for research that is made available to the broader scientific community.

Table 2.

Current literature on long-term outcomes of interest in cancer survivors—strengths and limitations of a CCSS paradigm

Outcome of interestCCSSCurrent literature in outcomes after adult-onset cancer
Subsequent malignant neoplasms (except t-MDS/AML)   
    Magnitude of risk with accuracy Yes (14, 15) Registry data with risk of underreporting (16) 
    Demographic and clinical risk factors Yes (14, 15) Yes 
    Relationship with chemotherapy dose Yes (14, 15) Registry data—limited information re therapeutic exposures 
    Identification of radiation dose response Yes (17) Registry data—limited information regarding radiation details 
    Modification of risk with comorbidities, life-style exposures, family history Yes (15) Registry data—limited information linked to comorbidities 
  Clinical trials—selection bias, follow-up issues, small sample 
    Examination of role of genetic susceptibility Yes (18) Lack of infrastructure to correlate biospecimens with outcomes 
Therapy-related myelodysplasia/acute myeloid leukemia   
    Magnitude of risk, demographic and clinical risk factors, relationship with chemotherapy dose No: study design precludes study of events in first 5 y of diagnosis with high fatality rates Yes: extremely short latency, limited “at risk period”—conducive to studies using clinical trial (19) or registry data (20) 
    Studies to identify predictors/biomarkers before occurrence of subsequent malignant neoplasm (SMN) No: study design precludes longitudinal data collection before occurrence of event of interest No: lack of infrastructure for conduct of such studies 
Cardiovascular and pulmonary complications (congestive heart failure, coronary heart disease, stroke, pulmonary compromise)   
    Magnitude of risk of congestive heart failure, pulmonary compromise, stroke Yes: self-report (risk of misclassification if no validation; refs. 21-23) Clinical trials—selection bias, follow-up issues, limited sample size (24); small convenience samples (25-28); registry data (29, 30) 
    Demographic and clinical risk factors Yes (21, 22) Clinical trials—selection bias, follow-up issues, limited sample size 
    Relationship with chemotherapy dose Yes (21, 22) Clinical trials—selection bias, follow-up issues, limited sample size 
    Relationship with radiation dose Yes (21, 22) Registry data — with limited information regarding radiation details 
    Modification of risk with comorbidities, life-style exposures, family history Yes (21) Clinical trials—selection bias, follow-up issues, limited sample size 
    Examination of role of genetic susceptibility Yes (21) Lack of infrastructure to correlate biospecimens with outcomes 
    Type of pulmonary compromise No: self-report precludes identification of specific types Small studies—conflicting results 
    Asymptomatic cardiac dysfunction No Clinical trials—selection bias, follow-up issues, limited sample size 
    Progression of disease with serial follow-up No Clinical trials—selection bias, follow-up issues, limited sample size 
Cognitive function   
    Special education needs, return to work Yes (31) Yes (32) 
    Demographic and clinical risk factors Yes (31) Yes (33) 
    Relationship with chemotherapy dose Yes (31) Small samples preclude association with specific therapeutic agents 
    Impact on specific domains No: study design precludes testing Small samples, nonstandardized instruments, conflicting results 
    Natural course of cognitive function No: study design is cross-sectional Small samples 
Endocrine (hypothyroidism, hypogonadism, infertility, premature menopause, obesity, diabetes)   
    Magnitude of risk Yes: self-report (risk of misclassification if no validation; refs. 34, 35) Yes (limited to certain cancer sites; refs. 36, 37) 
    Demographic and clinical risk factors Yes (34) Yes 
    Relation with chemotherapy/radiation dose Yes (34) Limited information regarding chemotherapy/radiation details 
    Pregnancy outcomes Yes (38, 39) Yes (limited to certain cancer sites; ref. 40) 
Health status of cancer survivors   
    Comparison with noncancer population Yes (41) Limited data 
    Demographic and clinical risk factors Yes (41) Limited data (42) 
    Survivors' knowledge about cancer, treatment Yes (43) Limited data 
Health-related screening Yes (44) Yes 
Renal and hepatic dysfunction   
    Identification of specific types of renal compromise (glomerular vs tubular defect) No: self-report precludes identification of specific types Clinical trials—selection bias, follow-up issues, limited sample size 
    Identification of specific types of hepatic dysfunction (cirrhosis vs chronic active hepatitis), association with hepatitis B or C No: self-report precludes identification of specific types Clinical trials—selection bias, follow-up issues, limited sample size 
Psychosocial outcomes (health-related quality of life, fatigue, sleep disturbance, depression, anxiety, stress)   
    Magnitude of risk Yes (45, 46) Yes (reviewed in refs. 4, 47-49) 
    Demographic and clinical risk factors Yes (46) Yes (reviewed in ref. 4) 
    Relation with chemotherapy/radiation dose Yes (46) Yes 
    Trajectory of recovery after diagnosis No Yes 
Patterns of healthcare use Yes (50) Yes (51) 
    Burden of morbidity Yes (7) Limited data (52) 
    Cause-specific late mortality Yes (53) Data limited to specific populations (25, 54, 55) 
    High risk behaviors Yes (56) Clinical trials—selection bias, follow-up issues, limited sample size; registry data—with limited information linked to high-risk behaviors 
Outcome of interestCCSSCurrent literature in outcomes after adult-onset cancer
Subsequent malignant neoplasms (except t-MDS/AML)   
    Magnitude of risk with accuracy Yes (14, 15) Registry data with risk of underreporting (16) 
    Demographic and clinical risk factors Yes (14, 15) Yes 
    Relationship with chemotherapy dose Yes (14, 15) Registry data—limited information re therapeutic exposures 
    Identification of radiation dose response Yes (17) Registry data—limited information regarding radiation details 
    Modification of risk with comorbidities, life-style exposures, family history Yes (15) Registry data—limited information linked to comorbidities 
  Clinical trials—selection bias, follow-up issues, small sample 
    Examination of role of genetic susceptibility Yes (18) Lack of infrastructure to correlate biospecimens with outcomes 
Therapy-related myelodysplasia/acute myeloid leukemia   
    Magnitude of risk, demographic and clinical risk factors, relationship with chemotherapy dose No: study design precludes study of events in first 5 y of diagnosis with high fatality rates Yes: extremely short latency, limited “at risk period”—conducive to studies using clinical trial (19) or registry data (20) 
    Studies to identify predictors/biomarkers before occurrence of subsequent malignant neoplasm (SMN) No: study design precludes longitudinal data collection before occurrence of event of interest No: lack of infrastructure for conduct of such studies 
Cardiovascular and pulmonary complications (congestive heart failure, coronary heart disease, stroke, pulmonary compromise)   
    Magnitude of risk of congestive heart failure, pulmonary compromise, stroke Yes: self-report (risk of misclassification if no validation; refs. 21-23) Clinical trials—selection bias, follow-up issues, limited sample size (24); small convenience samples (25-28); registry data (29, 30) 
    Demographic and clinical risk factors Yes (21, 22) Clinical trials—selection bias, follow-up issues, limited sample size 
    Relationship with chemotherapy dose Yes (21, 22) Clinical trials—selection bias, follow-up issues, limited sample size 
    Relationship with radiation dose Yes (21, 22) Registry data — with limited information regarding radiation details 
    Modification of risk with comorbidities, life-style exposures, family history Yes (21) Clinical trials—selection bias, follow-up issues, limited sample size 
    Examination of role of genetic susceptibility Yes (21) Lack of infrastructure to correlate biospecimens with outcomes 
    Type of pulmonary compromise No: self-report precludes identification of specific types Small studies—conflicting results 
    Asymptomatic cardiac dysfunction No Clinical trials—selection bias, follow-up issues, limited sample size 
    Progression of disease with serial follow-up No Clinical trials—selection bias, follow-up issues, limited sample size 
Cognitive function   
    Special education needs, return to work Yes (31) Yes (32) 
    Demographic and clinical risk factors Yes (31) Yes (33) 
    Relationship with chemotherapy dose Yes (31) Small samples preclude association with specific therapeutic agents 
    Impact on specific domains No: study design precludes testing Small samples, nonstandardized instruments, conflicting results 
    Natural course of cognitive function No: study design is cross-sectional Small samples 
Endocrine (hypothyroidism, hypogonadism, infertility, premature menopause, obesity, diabetes)   
    Magnitude of risk Yes: self-report (risk of misclassification if no validation; refs. 34, 35) Yes (limited to certain cancer sites; refs. 36, 37) 
    Demographic and clinical risk factors Yes (34) Yes 
    Relation with chemotherapy/radiation dose Yes (34) Limited information regarding chemotherapy/radiation details 
    Pregnancy outcomes Yes (38, 39) Yes (limited to certain cancer sites; ref. 40) 
Health status of cancer survivors   
    Comparison with noncancer population Yes (41) Limited data 
    Demographic and clinical risk factors Yes (41) Limited data (42) 
    Survivors' knowledge about cancer, treatment Yes (43) Limited data 
Health-related screening Yes (44) Yes 
Renal and hepatic dysfunction   
    Identification of specific types of renal compromise (glomerular vs tubular defect) No: self-report precludes identification of specific types Clinical trials—selection bias, follow-up issues, limited sample size 
    Identification of specific types of hepatic dysfunction (cirrhosis vs chronic active hepatitis), association with hepatitis B or C No: self-report precludes identification of specific types Clinical trials—selection bias, follow-up issues, limited sample size 
Psychosocial outcomes (health-related quality of life, fatigue, sleep disturbance, depression, anxiety, stress)   
    Magnitude of risk Yes (45, 46) Yes (reviewed in refs. 4, 47-49) 
    Demographic and clinical risk factors Yes (46) Yes (reviewed in ref. 4) 
    Relation with chemotherapy/radiation dose Yes (46) Yes 
    Trajectory of recovery after diagnosis No Yes 
Patterns of healthcare use Yes (50) Yes (51) 
    Burden of morbidity Yes (7) Limited data (52) 
    Cause-specific late mortality Yes (53) Data limited to specific populations (25, 54, 55) 
    High risk behaviors Yes (56) Clinical trials—selection bias, follow-up issues, limited sample size; registry data—with limited information linked to high-risk behaviors 

Recognizing these strengths, it is important to acknowledge the fact that the CCSS relies on self-report of outcomes and certain questions remain to be answered; these are detailed in Table 2. For example, the study design precludes understanding the natural course of asymptomatic cardiac dysfunction or the nature of hepatic dysfunction or the prevalence of osteoporosis—because all of these outcomes are asymptomatic until they are fairly advanced in their disease course. These limitations notwithstanding, the CCSS has enriched the childhood cancer survivorship literature in unprecedented ways and has been adopted as a model to study childhood cancer survivorship by several other countries. 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 (10, 11). The infrastructure developed for these projects may provide platforms for expanded research on cancer survivors, although these might take some time to mature because of the prospective nature of the cohorts.

The population of cancer survivors is growing at the rate of 2% per year, and there is, therefore, a sense of urgency, as well as a moral obligation, to understand the health-related challenges faced by this seemingly vulnerable group of individuals to optimize their long-term care. Comprehensive and well-designed survivorship research can be translated into clinical practice through development of evidence-based clinical care guidelines and through development, testing, and implementation of intervention strategies designed to prevent or minimize the effect of treatment–related adverse outcomes (Fig. 2). Currently, follow-up care relevant to survivorship outcomes is neither standardized nor guideline- or evidence-based for most adult-onset cancers, and optimal practices have yet to be defined. The American Society of Clinical Oncology Cancer Survivorship Expert Panel chose two of the most common, well-known, and well-studied late effects—cardiac and pulmonary dysfunction—to provide the evidence to form the basis for the evidence-based clinical practice guidelines. Yet, after rigorous evaluation of the evidence, it was concluded that the evidence was not sufficient to support evidence-based guidelines (12). There is therefore insufficient evidence on which to base evaluation for and management of these relatively common problems.

Figure 2.

Survivorship issues—future direction.

Figure 2.

Survivorship issues—future direction.

Close modal

Although evidence on which to base management of cancer survivors may not be currently available, consensus guidelines from an expert panel can serve as a starting point by standardizing care. It then becomes possible to study the effect of the guidelines on care delivered, thereby gaining the evidence needed to create subsequent iterations of the guidelines. Through this process, the critical accumulation of data will then form the basis of truly evidence-based guidelines. In the meantime, consensus guidelines can educate the health care provider about the unique needs of cancer survivors and prevent overutilization or underutilization of screening tests. The Children's Oncology Group has developed such guidelines for the long-term follow-up of childhood cancer survivors (13). However, the underpinnings of the Children's Oncology Group Long-term Follow-up Guidelines is the large body of evidence in the literature describing the magnitude of risk of the adverse events, clear associations between specific therapeutic exposures and the adverse events, and finally identifying those at highest risk of the adverse events described by their sociodemographic, clinical, and therapeutic exposure characteristics. Creation of similar follow-up guidelines for the adult cancer survivors will require research endeavors that assist in describing the magnitude of risk and associated risk factors for the late-occurring adverse events in this population—an issue that needs to be addressed with a clear sense of urgency.

No potential conflicts of interest were disclosed.

1
Hewitt M, Greenfield S, Stovall E. Cancer patient to cancer survivor: Lost in Transition. Washington DC, Committee on Cancer Survivorship: Improving Care and Quality of Life, National Cancer Policy Board, Institute of Medicine, and National Research Council, National Academies Press; 2006.
2
Anonymous. Cancer survivors: living longer, and now, better.
Lancet
2004
;
364
:
2153
–4.
3
Edwards BK, Howe HL, Ries LA, et al. Annual report to the nation on the status of cancer, 1973–1999, featuring implications of age and aging on U S. cancer burden.
Cancer
2002
;
94
:
2766
–92.
4
Ayanian JZ, Jacobsen PB. Enhancing research on cancer survivors.
J Clin Oncol
2006
;
24
:
5149
–53.
5
Geenen MM, Cardous-Ubbink MC, Kremer LCM, et al. Medical assessment of adverse health outcomes in long-term survivors of childhood cancer.
JAMA
2007
;
297
:
2705
–15.
6
Bhatia S, Robison LL. Late-effects among survivors of leukemia and lymphoma during childhood and adolescence.
Br J Haematol
2003
;
122
:
345
–9.
7
Oeffinger KC, Mertens AC, Sklar C, et al. Chronic health conditions in adult survivors of childhood cancer.
N Engl J Med
2006
;
355
:
1572
–82.
8
Ganz PA. Monitoring the physical health of cancer survivors: a survivorship-focused medical history.
J Clin Oncol
2006
;
24
:
5105
–11.
9
Robison LL, Mertens AC, Boice JD, et al. Study design and cohort characteristics of the Childhood Cancer Survivor Study: a multi-institutional collaborative project.
Med Pediatr Oncol
2002
;
38
:
229
–39.
10
Ayanian JZ, Chrischilles EA, Fletcher RH, et al. Understanding cancer treatment and outcomes: the Cancer Care Outcomes Research and Surveillance Consortium.
J Clin Oncol
2004
;
22
:
2992
–6.
11
Wagner EH, Greene SM, Hart G, et al. Building a research consortium of large health systems: The Cancer Research Network.
J Natl Cancer Inst Monogr
2005
;
35
:
3
–11.
12
Carver JR, Shapiro CL, Ng A, et al. American Society of Clinical Oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects.
J Clin Oncol
2007
;
25
:
3991
–4008.
13
Landier W, Bhatia S, Eshelman DA, et al. Development of risk-based guidelines for pediatric cancer survivors: the Children's Oncology Group Long-term Follow-up Guidelines from the Children's Oncology Group Late Effects Committee and Nursing Discipline.
J Clin Oncol
2004
;
22
:
4979
–90.
14
Neglia J, Friedman D, Yasui Y, et al. Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study.
J Natl Cancer Inst
2001
;
93
:
618
–29.
15
Kenney LB, Yasui YY, Inskip PD, et al. Breast cancer after childhood cancer: a report from the Childhood Cancer Survivor Study.
Ann Intern Med
2004
;
141
:
590
–7.
16
Curtis RE, Freedman DM, Ron E, et al. New malignancies among cancer survivors: SEER cancer registries, 1973–2000. Bethesda (MD): National Cancer Institute; 2006.
17
Ronckers CM, Sigurdson AJ, Stovall E, et al. Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers.
Radiat Res
2006
;
166
:
618
–28.
18
Mertens AC, Mitby PA, Radloff G, et al. XRCC1 and glutathione-S-transferase gene polymorphisms and susceptibility to radiotherapy-related malignancies in survivors of Hodgkin disease.
Cancer
2004
;
101
:
1463
–72.
19
Smith RE, Bryant J, DeCellis A, et al. Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and Bowel Project Experience.
J Clin Oncol
2003
;
21
:
1195
–204.
20
Hershman D, Neugut AI, Jacobson JS, et al. Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy.
J Natl Cancer Inst
2007
;
99
:
196
–205.
21
Blanco JG, Leisenring W, Davies SM, et al. Genetic polymorphisms in CBR3 and NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer.
Cancer
2008
;
12
:
2789
–95.
22
Mertens A, Yasui Y, Liu Y, et al. Pulmonary complications in survivors of childhood and adolescent cancer. a report from the Childhood Cancer Survivor Study.
Cancer
2002
;
95
:
2431
–41.
23
Bowers DC, Liu Y, Leisenring W, et al. Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: a report from the Childhood Cancer Survivor Study.
J Clin Oncol
2006
;
24
:
5277
–82.
24
Bonneterre J, Roche H, Kerbrat P, et al. Long-term cardiac follow-up in relapse-free patients after six courses of fluorocil, epirubicin, and cyclophosphamide with either 50 or 100 mg of epirubicin, as adjuvant therapy for node positive breast cancer. French adjuvant study group.
J Clin Oncol
2004
;
22
:
3070
–9.
25
Brusamolino E, Baio A, Orlandi E, et al. Long-term events in adult patients with clinical stage IA-IIA non-bulky Hodgkin's lymphoma treated with four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine and adjuvant radiotherapy: a single institution 15-year follow-up.
Clin Cancer Res
2006
;
12
:
6487
–93.
26
Hequet O, Le OH, Moullet I, et al. Subclinical late cardiomyopathy after doxorubicin therapy for lymphoma in adults.
J Clin Oncol
2004
;
22
:
1864
–71.
27
Shapiro CL, Hardenbergh PH, Gelman R, et al. Cardiac effects of adjuvant doxorubicin and radiaion therapy in breast cancer patients.
J Clin Oncol
1998
;
16
:
3493
–501.
28
Sampath S, Schultheiss TE, Wong J. Dose response and factors related to interstitial pneumonitis after bone marrow transplant.
Int J Radiat Oncol Biol Phys
2005
;
63
:
876
–84.
29
Doyle JJ, Neugut AI, Jacobson JS, et al. Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study.
J Clin Oncol
2005
;
23
:
8597
–605.
30
Woodward WA, Giordano SH, Duan Z, et al. Supraclavicular radiation for breast cancer does not increase the 10-year risk of stroke.
Cancer
2006
;
106
:
2556
–62.
31
Mitby PA, Robison LL, Whitton JA, et al. Utilization of special education services and educational attainment among long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.
Cancer
2003
;
97
:
1115
–26.
32
Satariano WA, DeLorenze GN. The likelihood of returning to work after beast cancer.
Public Health Rep
1996
;
111
:
236
–41.
33
Tannock IF, Ahles TA, Ganz PA, et al. Cognitive impairment associated with chemotherapy for cancer: Report of a workshop.
J Clin Oncol
2004
;
22
:
2233
–9.
34
Sklar C, Whitton JA, Mertens AC, et al. Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study.
J Clin Endocrinol Metab
2000
;
85
:
3227
–32.
35
Sklar C, Mertens AC, Mitby PA, et al. Premature menopause in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.
J Natl Cancer Inst
2006
;
98
:
890
–6.
36
Leining MG, Gelber S, Rosenberg R, et al. Menopausal-type symptoms in young breast cancer survivors.
Ann Oncol
2006
;
17
:
1777
–82.
37
Herman D, Ganz PA, Petersen L, et al. Obesity and cardiovascular risk factors in younger breast cancer survivors: The Cancer and Menopause Study.
Breast Cancer Res Treat
2005
;
93
:
13
–23.
38
Green DM, Whitton JA, Stovall E, et al. Pregnancy outcome of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.
Am J Obst Gynecol
2002
;
1887
:
1070
–80.
39
Green DM, Whitton JA, Stovall E, et al. Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.
J Clin Oncol
2003
;
21
:
716
–21.
40
Ganz PA, Greendale GA, Petersen L, et al. Breast cancer in younger women: repoductive and late health effects of treatment.
J Clin Oncol
2003
;
21
:
4184
–93.
41
Hudson MM, Mertens AC, Yasuai YY, et al. Health status of adults who are long-term childhood cancer survivors: a report from the Childhood Cancer Survivor Study.
JAMA
2003
;
290
:
1583
–92.
42
Ganz PA, Moinpour CM, Pauler DK, et al. Health status and quality of life in patients with early-stage Hodgkin's disease treated on Southwest Oncology Group Study 9133.
J Clin Oncol
2003
;
21
:
3512
–9.
43
Kadan-Lottick NS, Robison LL, Gurney JG, et al. What do childhood cancer survivors know about their past diagnosis and treatment?
JAMA
2002
;
287
:
1832
–9.
44
Yeazel MW, Oeffinger KC, Gurney JG, et al. The cancer screening practices of adult survivors of childhood cancer.
Cancer
2004
;
100
:
631
–40.
45
Zebrack B, Gurney J, Oeffinger K, et al. Psychological outcomes in long-term survivors of childhood brain cancer: a report from the Childhood Cancer Survivor Study.
J Clin Oncol
2004
;
22
:
999
–1006.
46
Zebrack BJ, Zeltzer LK, Whitton JA, et al. Psychological outcomes in long-term survivors of childhood leukemia, Hodgkin's disease and non-Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study.
Pediatrics
2002
;
110
:
42
–52.
47
Mandelblatt J, Armetta C, Yabroff KR, et al. Descriptive review of the literature on breast cancer outcomes: 1990 through 2000.
J Natl Cancer Inst Monogr
2004
;
33
:
8
–44.
48
Ganz PA, Kwan L, Stanton AL, et al. Quality of life at the end of primary treatment of breast cancer: first results from the Moving Beyond Cancer randomized trial.
J Natl Cancer Inst
2004
;
96
:
376
–87.
49
Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors.
N Engl J Med
2008
;
358
:
1250
–61.
50
Oeffinger KC, Mertens AC, Hudson MM, et al. Healthcare of young adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.
Ann Family Med
2004
;
2
:
61
–70.
51
Earle CC, Neville BA. Under use of necessary care among cancer survivors.
Cancer
2004
;
101
:
1712
–9.
52
Yabroff KR, Lawence W, Clauser S, et al. Burden of illness in cancer survivors: findings from a population-based national sample.
J Natl Cancer Inst
2004
;
96
:
1322
–30.
53
Mertens AC, Yasui YY, Neglia JP, et al. Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study.
J Clin Oncol
2001
;
19
:
3163
–72.
54
Bhatia S, Francisco L, Baker KS, et al. Late mortality in two-year survivors of autologous hematopoietic cell transplantation (HCT): report from the BMT Survivor Study (BMTSS).
Blood
2005
;
105
:
4215
–22.
55
Bhatia S, Francisco L, Carter A, et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study.
Blood
2007
;
110
:
3784
–92.
56
Emmons K, Li FP, Whitton JA, et al. Predictors of smoking initiation and cessation among childhood cancer survivors: a report from the Childhood Cancer Survivor Study.
J Clin Oncol
2002
;
20
:
1608
–16.