Historically, pediatric and adult cancer services have operated relatively independently of one another, with each developing its own idiosyncratic model of care, as discussed in Sect. 2.2 of this chapter. In many regions there are overlapping age limits allowing AYAs between age 15 and 20 years (and occasionally up to 30) to access either site. There are increasing data suggesting that the choice of healthcare setting influences outcome. Specifically, AYAs with tumors more commonly seen in childhood appear to have a survival advantage when treated in a pediatric center, while those with carcinomas and other “adult” tumors fare better when treated by adult oncologists [15, 16]. Although differences in regimens of chemotherapy appear to explain much of the variation in outcome in ALL between pediatric and adult centers, the survival benefit may relate also to pediatric oncologists’ greater familiarity with the complex protocols, centralization of care to tertiary/academic centers, and rigid adherence to prescribed dose and schedule [17]. These factors may explain the results of a retrospective review of German Ewing sarcoma trials which found a survival advantage for older AYAs treated in a pediatric center compared with adult centers, despite all patients receiving the same protocol of therapy [18]. Hence, it is likely that site of care is a proxy measure for clinical expertise in both disease-specific management and the psychosocial care of AYAs.

The importance of access to clinical expertise and centralized care is emphasized by several registry studies of AYAs with cancer which have reported that the adverse impact of age is abrogated by treatment at National Cancer Institute (NCI)-Designated Comprehensive Care Centers or Children’s Oncology Group institutions [15, 19–21] in the United States. While the majority of children with cancer received treatment in such centers, the proportion fell to approximately 38 % of 15- to 21-year-olds and a mere 10 % of 22- to 39-year-olds. This difference was particularly pronounced for older adolescents with low socioeconomic status, public or no insurance, and increased distance to care.

Site of care is also a strong determinant of access to clinical trials. While it is unclear whether participation in a cancer clinical trial is associated with improved survival at an individual level [22], there is no question that collaborative group trials have facilitated stepwise improvements in survival for many cancers at a population level and that AYAs have been historically underrepresented in such studies [23–27].

Decisions regarding site of care are determined frequently by the initial referring physician, who will often not be familiar with the issues discussed in this chapter, given the relative rarity of cancer in AYAs. Consequently, patterns of referral are often arbitrary and based primarily on the patient’s age, with the specialty of the referring physician, their years in practice, and location of training also potentially influencing this decision. While studies from Utah and Ohio found that 15- to 19-year-olds with “pediatric”-type tumors were somewhat more likely to be referred to pediatric oncologists than those with tumors more common in adults, two-thirds of patients from this age group were never referred to a pediatric oncologist. Furthermore, utilization of pediatric centers dropped with each additional year of age [28, 29]. This is despite consensus guidelines from the American Academy of Pediatrics [30] and the American Federation of Clinical Oncologic Societies [31] recommending that pediatric oncologists are the most appropriate providers for adolescent cancer patients.

Although there is broad agreement that pediatric oncologists are best placed to care for adolescents with cancer, the picture is less clear for young adults. Pediatric oncologists probably have the most clinical expertise in managing pediatric-type tumors, including ALL, rhabdomyosarcoma, Ewing sarcoma and osteosarcoma, and medulloblastoma, but pediatric hospitals are often not a developmentally appropriate location in which to treat young adults. Equally, one could argue that many adult hospitals lack the time and expertise to address the psychological and social challenges faced by this age group. The development of Teenage and Young Adult Cancer Units in the United Kingdom, and subsequent adaptations in other countries, may provide an ideal combination of disease-specific and psychosocial expertise as well as an age-appropriate environment. This is reflected in the British National Institute for Health and Care Excellence guidelines recommending that “young people (aged 16–24 years) with cancer have their diagnosis, treatment and support agreed and delivered by a cancer-site-specific multidisciplinary team and a young adult multidisciplinary team” [32]. The Clinical Oncology Society of Australia has released similar guidelines [33].

Extrapolating from the evidence presented above, care by physicians with expertise in AYA oncology may improve outcomes, but as yet there is little empiric evidence to support this hypothesis. The concept of what constitutes “expertise” in AYA oncology is still evolving but could be assessed by specific training (pediatric, medical, or AYA oncology), practice volume (number of AYAs seen at a center or by a provider), expertise in the cancer diagnoses that affect AYAs (regardless of patient age), and expertise in the psychosocial and developmental needs of AYAs [34, 35]. Preferably, AYA patients should have care from clinicians possessing both age-appropriate and tumor-specific expertise.

AYA oncology training programs are continuing to be developed in medical, social work, mental health, and nursing disciplines. Online and conference AYA educational opportunities to earn academic credits or continuing medical education points are becoming increasingly available for all providers (e.g., LIVESTRONG’s “Focus Under 40”), and online courses are offered internationally through Coventry University and the University of Melbourne. For physicians in the United States, a very limited number of “AYA fellowship” programs have been implemented, but are not yet recognized by credentialing boards. Until there is AYA-specific training and credentialing, the debate whether pediatric or adult medical oncologists are better placed to care for AYAs will probably continue.

Much of this discussion has focused on optimizing access to the best possible medical treatment, but AYAs with cancer also have unique psychological and social needs related to their life stage which are not always well met by either pediatric or adult models of care. As such, access to age-appropriate psychosocial care is crucial for this age group, with the critical elements summarized by Zebrack et al. [36] (Table 20.2). Anecdotal reports suggest that young people, their families, and the treating team greatly value the involvement of designated AYA cancer care coordinators (with a nursing or social work background). These health professionals can guide the patient through the often fragmented healthcare system, ensure that psychosocial issues are being addressed, help advocate for the patient, and provide general adolescent health guidance (e.g., sexual health, substance use). This is particularly important for the majority of AYAs who are treated at non-pediatric institutions, where a culture of holistic care is less engrained and self-management skills are often presumed. Early referral to psychologists and/or social workers with experience in treating AYAs is likely to help alleviate distress, promote coping strategies, and possibly support adherence to treatment. Access to other allied health staff such as an educational/vocational counselor, exercise physiologist, and dietician may assist in the transition to healthy survivorship, and it is acknowledged increasingly that exploring fertility preservation options is a fundamental component of AYA cancer care [36, 37]. AYAs with cancer endorse the benefits of meeting other young people with cancer universally [38], emphasizing the importance of facilitating access to peer support programs coordinated by not-for-profit organizations, such as Stupid Cancer (United States), CanTeen (Australia), and Teenage Cancer Trust (United Kingdom).

Research in this area is sparse, largely because of the lack of consensus on the most appropriate therapy for specific cancers in the AYA population. Many studies document variation by age in the treatment of cancer; for example, AYA sarcoma patients characteristically receive less intensive therapy than children [39–41], younger breast cancer patients are more likely to undergo mastectomy [42], and younger rectal cancer patients receive radiation more frequently [43]. As noted above, there is consensus that a pediatric-based treatment is the appropriate therapy for a young AYA with ALL; however, there is less agreement on whether this pertains to AYAs aged 30–40 as well.

The AYA HOPE Study Collaborative Group reported recently that 25 % of a population-based sample of AYA did not receive “appropriate” initial courses of treatment, as defined by expert clinical consensus [44]. In multivariate analysis, clinical trial participation and cancer type were associated significantly with appropriate treatment, with 100 % of early stage male germ cell tumor, 79 % of sarcoma, and 56 % of ALL patients receiving appropriate therapy.

This study highlights the paucity of empirical research on the appropriateness of such variation in treatment. In some clinical cases, less therapy may be more appropriate, whereas in other cases, AYAs should be treated equally or even more intensively than children. Translational and clinical research should not assume that the biology of specific cancers in AYAs is the same as in other age groups, and host genetic variations influencing treatment response may also differ in AYAs with cancer [45]. For example, the incidence of Philadelphia-like ALL increases from <3 % of children to 27 % of young adults with ALL [46]. Additionally, specific germline susceptibility alleles are overrepresented in AYAs, suggesting an inherited predisposition to high-risk disease in this age group [47]. Likewise, it is plausible that tumor genetics and host polymorphisms contribute to a more aggressive disease phenotype in AYAs who develop the epithelial cancers that more characteristically occur in older individuals. Furthermore, AYAs exhibit distinct pharmacokinetic differences to children or older adults, which may contribute to age-specific variation in drug efficacy and toxicities [48]. Whether it is appropriate to differentiate therapy for AYAs by age alone or whether more emphasis should be placed on other biologic parameters that may sometimes be correlated by age, such as hormone receptor status in breast cancer, will have to be determined for each cancer type. Clearly, this area is ripe for future translational research.

There is substantial evidence of specific clinical and psychosocial features, and also specific challenges in patient’s management, that mark out being an AYA with cancer. Patients in this age group have specific clinical features because of their cancer types, tumor, and host biology; because of the insufficient awareness that cancer may occur in this age group and the complex diagnostic pathways; and because of the specific psychological and social characteristics that care providers must address adequately (Table 20.3) [92–99]. On the other hand, there is growing evidence that these patient features combine unfavorably with the features of many current healthcare systems (Table 20.4) [91, 100–110].

One of the main challenges for young people with cancer is the possibility to continue to live as normal a life as possible and to achieve developmental tasks. This critical concept needs to be taken into account when developing age-specific models of care. In this group, people change their perception of the world and need to test their limits. A recent review described brilliantly the AYA’s world with the reference to the famous phrase of “sex, drugs, and rock ‘n’ roll” [111]. Care providers should be able to address the need of young people to live their experiences and rites of passage, that cannot be postponed due to the event of a cancer diagnosis. Care providers should be able to establish an open relationship with their patients to help them to revisit these aspects in the light of their cancer history. Young patients need to feel comfortable disclosing sensitive matters. Talking about “sex” – about sexual identity and sexual practices but also sexual dysfunction related to the disease or treatment – may be particularly complicated for a teenager in front of a doctor. A sensitive, nonjudgmental, and confidential relationship is essential also regarding “drugs” – alcohol and drug exploration and use. Clinicians must be aware of aspects such as the negative impact of alcohol and drug use (or abuse) in relation to the patient’s health, the interactions with medical drugs, and the associated psychosocial morbidity; but they should be able to address this issue in a timely and appropriate manner, avoiding a paternalistic approach and prohibition that, for example, may have a negative impact on treatment adherence. Alcohol consumption and recreational drug use may have a role for socialization and for feeling normal and being part of the crowd. An adequate balance should be considered appropriately to help young people in developing their sense of self and their feelings of connection to the world. The “rock ‘n’ roll” lifestyle distinguishes young people from children and from older adults. The crucial concept that care providers dealing with AYAs should have in their mind is that a patient is first a normal young person who happens to have a cancer: this concept should be at the foundation of the model of care. Promoting normalcy means adequate spaces and rules in the ward to facilitate the relationship with peers and prevent the isolation that long periods of hospitalization may imply: social zone and multifunctional spaces with technical equipment (TVs, computers, musical instruments, books, magazines, and DVDs appealing to the age group concerned), for example, as well as kitchen/dining zone or “chill-out” zone. It means accessible visiting times and easy access to the hospital. It means the availability of activities and events as take away evenings. But it means also the opportunity to respect the need of privacy and the possible wish to refuse the involvement in social activities.

A further critical aspect relates to what young people say they need. In designing and delivering services, it is essential to take the experiences and views of patients into account. It is important that the young people are given a “voice and a choice” in their care, as this helps to inform and underpin everything that is developed for them. Given the opportunity, young people will say what they want from services and those who provide them.

Pediatric oncologists and adult medical oncologists usually adopt different organization models, particularly as concerns interaction with the patient. With a rough generalization, it could be said that the pediatric model is family focused, while the adult model seems to be disease focused (Fig. 20.1).

Since AYAs are neither children nor older adults, and yet share many characteristics of both, it is not surprising that neither of the classic pediatric or adult models of care is ideally suited to meet the needs of AYA patients. Certainly, it remains to be seen whether a single, ideal “new” model of delivery of care should exist for AYA patients and whether it could feasibly be implemented. Alternatively, there should be discussion about what adjustments should be made to one or both systems to better meet the needs of the AYA patient [114].

Due to the complexity of their care and the variety of their psychosocial issues, a multidisciplinary approach is necessary. In addition to the routine group of specialties, this may well include nurse educators, navigators, fertility experts, social workers (especially skilled in employment and insurance counseling), teachers, psychologists, sexual consultants, and even a cosmetics expert (Fig. 20.1).

Given that teenagers and young adults develop a wide range of cancers that encompass both pediatric and adult types of tumors, the multidisciplinary team should include the expertise of both pediatric and adult medical oncology. Providing both of these skills remains a challenge. On the one hand, the direct presence in the team of both pediatric oncologists and adult medical oncologists may be an apparently easy solution. On the other hand, the figure of a “new” tailored healthcare provider – an AYA oncologist – may be advisable. Barriers exist for both solutions [91].

Establishing a genuine collaboration and shared ownership between pediatric oncologists and medical oncologists remains a difficult goal. There are different backgrounds, different priorities, and different models of working: even when they deal with similar diseases, pediatric and adult oncologists often adopt different classification, staging, and grading systems, as well as different practices relating, for example, to data collection – and consequent difficulties when it comes to sharing data. Though both may have much to gain from cooperating with one another, competition often exists. Historical experience showed that AYA dedicated programs have developed in some cases as an adjunct to the local adult oncology facility, while in other cases they have developed predominantly as an adjunct to pediatric oncology services. It has been less common for units to be developed by joint collaboration between adult and pediatric oncology teams.

The ultimate solution to develop oncologists (and oncology centers) specifically dedicated to the care of AYA patients – to create a new discipline, i.e., AYA oncology, with its own training programs, clinical and translational research, and national and international organizations – still remains a challenge. For example, current training for either pediatric or medical oncologists does not provide the necessary skill, and a modification of current fellowships would be necessary.

However, more than regarding the specific training needed for AYA oncology, the key unresolved issue remains whether, in practice, the AYA oncologist ought to cross all disease boundaries, treating breast cancer, melanoma, rhabdomyosarcoma, and leukemias with equal competence. Given the complexity of modern oncology, this seems unlikely. As a matter of fact, a tension continues to exist between providing centralized care in a unit specializing in a particular malignant disease or in a unit specializing in the care and needs of young people. It might be thought that the best solution for young people would be to create an environment that combines these elements to ensure that teenagers and young adults benefit from both. The optimal model may be a unit designed specifically for young people and staffed by a skilled multiprofessional team expert in both the care of teenagers and young adults and their diseases and committed to working in new ways. In this way, the role of the AYA oncologist may be complementary to these of pediatric and medical oncologists. Patients would be cared for in a unique space (inpatient and outpatient) with specially trained providers, within a culture that recognizes the various needs of young patients as well as the necessity to improve clinical trial enrollment [91].