Pediatr Blood Cancer 2008;50:1090–1093
REVIEW
Registration and Classification of Adolescent and Young Adult Cancer Cases
1,2
Brad H. Pollock, MPH, PhD
Cancer registries are an important research resource that facilitate
the study of etiology, tumor biology, patterns of delayed diagnosis
and health planning needs. When outcome data are included,
registries can track secular changes in survival related to improve-
ments in early detection or treatment. The surveillance, epidemiol-
ogy, and end results (SEER) registry has been used to identify major
gaps in survival for older adolescent and young adult (AYA) patients
compared with younger children and older adults. In order to
determine the reasons for this gap, the complete registration and
accurate classification of AYA malignancies is necessary. There are
inconsistencies in defining the age limits for AYAs although the
Adolescent and Young Adult Oncology Progress Review Group
Key words: classification; registration
INTRODUCTION
Disease registries are a fundamental resource for research.
Registries allow researchers to characterize the disease burden in
populations to provide clues about disease etiology; to plan for
needed health resources; and to evaluate the long-term impact of
prevention, early detection, and therapeutic interventions. Cancer
registries are important for the investigation of suspected clusters of
cancer, to evaluate the effectiveness of population-based mass
screening programs and to track secular changes in survival.
WHY REGISTER AND CLASSIFY
AYA MALIGNANCIES?
A central focus of the emerging field of adolescent and young
adult (AYA) oncology is differentiating characteristics of patients
diagnosed in this age group from those in earlier childhood and older
adulthood. The surveillance, epidemiology, and end results (SEER)
registry was used to produce a comprehensive monograph des-
cribing the incidence and survival patterns of older adolescents and
young adults aged 15–29 years [1]. Theoretically, registries can
facilitate the study of etiology, can shed light on biological
heterogeneity and variation in responsiveness to treatment, and
can be used to track long-term outcomes. Registries are needed to
characterize the degree of access to diagnostic and treatment
services in a population, and for health planning. Cancer registries
must include accurately classified diagnoses of malignant diseases,
detailed demographic and treatment information, and, ideally, track
outcomes. Analysis of SEER data has helped identify major gaps in
survival for older AYA patients compared with younger children and
older adults [2]. Even though the utility of complete cancer
registration and accurate diagnostic classification is evident, limited
attention has been focused on the unique aspects of registration and
classification of AYA cancers [3,4].
Older adolescents and young adults with cancer have not
demonstrated the gains in survival that have been experienced by
either younger or older patients [5]. This is referred to as the ‘‘AYA
Gap.’’ To begin to understand why this outcome gap exists,
registration and accurate classification of AYA malignancies is
ß 2008 Wiley-Liss, Inc.
DOI 10.1002/pbc.21462
3
* and Jillian M. Birch, MSc, PhD
proposed a definition of ages 15 through 39 years. The central
registration and classification issues for AYAs are case-finding,
defining common data elements (CDE) collected across different
registries and the diagnostic classification of these malignancies.
Goals to achieve by 2010 include extending and validating current
diagnostic classification schemes and expanding the CDE to support
AYA oncology research, including the collection of tracking infor-
mation to assess long-term outcomes. These efforts will advance
preventive, etiologic, therapeutic, and health services-related
research for this understudied age group. Pediatr Blood Cancer
2008;50:1090–1093. ß 2008 Wiley-Liss, Inc.
required. Population-based registries are important to generate
hypotheses about: (1) possible differences in tumor biology for
specific malignancies that affect AYAs and other age groups; (2)
differential impact of changes in treatment practices for AYAs in
contrast to other age groups; and (3) improvements in early
detection by examination of changes in stage distribution for AYAs
compared to other age groups. On a population basis, there is a need
to understand the socio-demographic characteristics of AYA
patients with cancer in order to identify the psychosocial, educa-
tional, and support needs for these individuals from the period of
being at risk for cancer through cancer diagnosis, active treatment,
and into survivorship [6].
A better understanding of why the AYA Gap exists is needed.
Reasons for this discrepancy remain unexplained. Our present lack
of knowledge may be related to our ability to fully count and
characterize AYA malignancies, lack of a universally accepted
diagnostic classification system for AYA cancers, and the paucity of
descriptive data collected at diagnosis that might better characterize
these diseases. Tumor specimens are not collected routinely on a
population basis; such samples, combined with information on
diagnostic classification, might help identify AYA-specific bio-
logical features. Across registries, comparisons are difficult because
of differences in the way cases are ascertained, different diagnostic
classification procedures, and varying levels of data collection
linking biological factors with diagnoses and outcomes [7].
— —————
1
Department of Epidemiology and Biostatistics, University of Texas
Health Science Center at San Antonio, San Antonio, Texas; 2San
Antonio Cancer Institute, San Antonio, Texas; 3Cancer Research UK,
Paediatric and Familial Cancer Research Group, Royal Manchester
Children’s Hospital, University of Manchester, Manchester, United
Kingdom
*Correspondence to: Brad H. Pollock, Department of Epidemiology
and Biostatistics, University of Texas Health Science Center at San
Antonio, 7703 Floyd Curl Drive, Mail Code 7933, San Antonio, TX
78249-2023. E-mail: bpollack@uthscsa.edu
Received 7 November 2007; Accepted 7 November 2007

The foundation for all large comprehensive cancer control
programs is accurate and timely identification, diagnostic classi-
fication, and registration of incident cancers and deaths. However,
little attention has focused on the AYA population. Registries can
link incidence, mortality, and sometimes prevalence and patient
survival with demographic, geographic and time pattern character-
istics. For example, descriptive epidemiologic analysis of cancer
registry information demonstrated the impact of secular changes in
tobacco exposure with a multi-decade decline in male lung cancer
incidence and increasing incidence in females. Registries can
identify targets for cancer control measures such as mass screen-
ing and interventions to increase access to diagnostic services.
Registries are also used to examine the long-term impact of cancer
control interventions. Unusual patterns of cancer occurrence can be
identified from registries to stimulate further causal investigations
[8,9]. For etiologic investigations, cancer registries can serve as a
source of case-finding. Unfortunately, direct use of registries to
address the unique health problems of the AYA population is
lacking.
WHAT IS MEANT BY ADOLESCENT/YOUNG
ADULT (AYA)?
There is no universally agreed upon definition of what ages are
included in the AYA designation. There is overlap between child,
adolescent and young adult categories. Typically, in oncology,
children are considered individuals under the age of 15 years.
However, the World Health Organization classifies a child as an
individual under 18 years of age. Functionally, adolescence is often
defined at the time of onset of puberty. However, in the developed
world, the age at the onset of puberty has steadily decreased over the
past several decades. Early adulthood begins with the attainment of
adult height and full reproductive maturity. When both physio-
logical as well as psycho-behavioral attributes are considered, early
adulthood equates to approximately 19 years of age in women and
21–25 years of age in men [8]. Thus adolescence can span 10–
25 years when considering both males and females. In the U.S.,
pediatric oncologists typically care for patients up to 21 years of age
and sometimes up to 30 years of age for patients with bone tumors,
but practices vary around the world. In Europe, pediatric practice is
restricted more commonly to under 15 or under 18 years of age. The
definition of the upper bounds of where ‘‘young adulthood’’ ends is
highly variable. Reported series have referenced individuals up to
24, 29, and even 39 years of age as young adults. This is reflected in
the variation of pediatric oncology practices, some of which are
based at children’s hospitals with mandated upper age limits of 18 or
21 years of age. The Adolescent and Young Adult Oncology
Progress Review Group, sponsored by the U.S. National Cancer
Institute and the Lance Armstrong Foundation, considered AYAs to
be those individuals diagnosed with cancer at ages 15 through
39 years [7]. In England the National Institute for Health and
Clinical Excellence published guidance on cancer services for
young people and made recommendations for those diagnosed
before 25 years of age [10].
CENTRAL REGISTRATION AND
CLASSIFICATION ISSUES
There are three central registration and classification issues for
AYA malignancies: case-finding; common data elements (CDE);
Pediatr Blood Cancer DOI 10.1002/pbc
Registration and Classification of Cancer Cases 1091
and diagnostic classification. Case-finding methods vary greatly,
with most registrations occurring in hospitals. In the developing
world, incidence figures are limited typically to reports from large
referral hospitals and may not represent the patterns of occurrence in
geographically-defined populations. In the industrialized world,
many countries have government-supported national cancer
registration schemes (e.g., United Kingdom, the Scandinavian
countries, and Canada) or cancer registration in defined geographic
areas within a country (e.g., United States, France, and Italy)
enabling the assembly of geographically-defined, population-based
cancer statistics [11]. In contrast to population-based registries,
published reports from hospital-based registries make inferences
about cancer occurrence rates that are potentially biased, in that only
referred patients are counted. Pediatric-specific cancer registries
often restrict registration to cases diagnosed under 15 years of age,
thereby missing a substantial proportion of AYA cases [12], making
the hospital—versus population-based registry disparity even
greater for the AYA age group [13].
The complement of information collected varies across different
population-based cancer registries. Often there is a minimal set of
required CDE. For example, in the U.S. and Canada, all states and
provinces collect a common set of variables defined by the North
American Association of Central Cancer Registries (NAACR).
This minimal data set does not include survival information nor does
it include detailed treatment information. European registries
consistently collect information on survival and may also include
treatment data [14]. Tumor-specific staging information is often not
recorded and important features of the tumor are usually accounted
for only in the diagnostic morphology code, leaving out many other
known prognostic biological factors. Such biological information
would be useful in accounting for differences in survival of AYAs
with a specific malignancy compared to other age groups. While
a minimum set of CDE is specified for all NAACR-certified
registries within the U.S., the subset that participate in the SEER
program (which covers approximately 26% of the U.S. population)
are required to collect a much more comprehensive set of variables
including detailed treatment information and outcome data. There
are few large population-based registries developed specifically for
pediatric malignancies and very few that focus primarily on AYA
malignancies. However, the EUROCARE program has produced an
overview of survival among AYA with cancer throughout Europe
[14]. For cancer research data exchange, the National Cancer
Institute (NCI) has defined a set of CDE to enhance collaboration
across treatment centers [15]. While useful for clinical research,
collection of this very comprehensive NCI-defined set of CDE
would far exceed the capacity of the majority of population-based
registries. In addition, our desire to expand the set of CDE collected
routinely in population-based registries is becoming ever more
limited in the U.S. and Canada due to increasing regulatory policies
and the threat of litigation. Many local institutional review boards
require full subject consent to collect even a minimal set of registry
information beyond what is collected currently by states and
provinces.
Diagnostic classification of AYA cancers presents a challenge.
Pediatric malignancies are characterized primarily by morphology;
carcinomas in this population are much less common. For pediatric
malignancies, the most common diagnostic coding system is the
International Classification of Diseases for Oncology (ICD-O) [16],
which includes coding for morphology and primary anatomic site.
The International Classification of Childhood Cancer [17] provides
1092 Pollock and Birch
a system for grouping ICD-O coded cases by diagnosis for analysis.
Adult cancers, which are predominantly carcinomas, are charac-
terized primarily by topography. For AYAs with cancer, Birch et al.
[4] proposed a morphology-based classification using 10 major
diagnostic groups defined by the ICD-O morphology codes (second
edition). Major diagnostic groups were further divided into sub-
groups based on the frequency of occurrence. For example, within
the major morphology category of carcinomas, diagnoses are
subdivided by primary site frequency of occurrence. Within the
carcinoma group, thyroid carcinomas are listed first, followed by
carcinomas of the head and neck, the genitourinary tract, the
gastrointestinal tract, and other and ill-defined carcinomas. This
combined morphology/site classification system better accounts for
more pediatric-like malignancies and more adult-like malignancies
that commonly affect the AYA age group. Using such a system as a
standard would facilitate comparisons of AYA cancer occurrence
across different cancer registries as well as aid in formulating
etiologic hypotheses [3].
REGISTRATION AND CLASSIFICATION
GOALS TO ACHIEVE BY 2010
Current diagnostic classification schemes for AYA malignancies
need to be extended and validated. Registries used to support AYA
oncology research need to be more comprehensive in the set of data
elements that are collected. Accurate tumor-specific staging,
including alternative staging systems such as the TNM system and
clinical-trial specific staging such as the International Neuro-
blastoma Risk Group Staging System, should be included.
Congenital abnormalities as well as the history of cancer in primary
and secondary degree relatives might also be included. Tumor-
specific biological information, such as cytogenetic and other
prognostic marker data, and accurate coding of tumor stage data
should be integrated into AYA cancer registries. Histopathological
diagnosis must be documented on all new AYA cancer cases.
Detailed morphology as well as primary site information should be
collected to allow for refinement of AYA-specific diagnostic
classification schemes. Finally, a set of CDE should be agreed upon
by international consensus of AYA oncology researchers to promote
sharing and pooling of data. The addition of such data elements will
complement existing population-based registries and will accelerate
research in AYA oncology.
In addition to the CDE collected currently, tracking identifiers
should be included to facilitate prospective tracing and surveillance
needed to assess long-term outcomes. Surveillance of AYA cancer
patterns requires greater depth and breadth of traditional surveil-
lance activities. Information such as health risk behaviors, quality of
care, economic factors, and patient-centered outcomes may be more
important than for other age groups [7]. Research challenges related
to patient privacy and confidentiality restrictions must be addressed
to facilitate long-term tracking of AYA subjects.
The pediatric cooperative groups in North America successfully
advanced the development and use of new therapies in childhood
cancer treatment. The majority of young children diagnosed with
cancer in most of the industrialized world are treated in institutions
which participate in cooperative clinical trials [13,18,19], a
phenomenon to which the improvement in survival for this age
group is largely attributed. Likewise, the relatively lower rate of
improvement in AYA survival can be ascribed to reduced access to
cooperative group clinical trials [20], with only 24% of incident
Pediatr Blood Cancer DOI 10.1002/pbc
cases aged 15–19 years seen at cooperative group-affiliated
institutions in the US [18]. In order to identify access barriers for
AYAs with cancer, enumeration of all incident cases from the
population is necessary along with a complete accounting of
enrollment onto treatment protocols. The Children’s Oncology
Group (COG) has formed the Children’s Cancer Research Network
(CCRN) to develop a unified cancer registry in North America [21].
Existing, national population-based cancer registries in Europe and
elsewhere should be encouraged to make maximum use of their data
on AYA by conducting targeted detailed studies in this age group.
The long-term plans of the CCRN are to link COG registration data
with existing state and provincial registries’ data. A similar national
initiative to link clinical, cancer registration, and other data in the
United Kingdom should be underway within the year. For AYA
patients with cancer, population-based cancer registries could
elucidate referral patterns and clinical trial participation to aid in the
development of interventions designed to increase access to state-
of-the-art therapies.
The value of cancer registries for AYA oncology research cannot
be overestimated. The first systematic evidence that there is an AYA
survival gap came from examination of SEER data. Likewise, the
hypothesis that the gap in the U.S. is related to lower accrual onto
clinical trials was also generated from SEER data. The challenge
before us is to develop infrastructure to register and accurately
classify all AYA malignancies in population-based registries with a
comprehensive set of data elements that will advance preventive,
etiologic, therapeutic, and health services-related research for this
understudied age group.
ACKNOWLEDGMENT
Dr. Pollock is supported by grants CA 95861, CA 098543, and
CA 054174 from the National Cancer Institute, National Institutes
of Health. Dr. Birch is a Cancer Research UK Professorial Fellow at
the University of Manchester.
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