Small Numbers,Big Challenges: Adolescent and Young Adult Cancer Incidence and Survival in New Zealand

Introduction

When it comes to adolescents and young adult (AYA) cancer services, New Zealand's geographical size, small population, cultural diversity, and the structure of its health system presents some unique challenges. Spread over two islands and with a land area equivalent to that of the United Kingdom, New Zealand's population is a comparatively small 4.6 million. Most cancer treatment is undertaken within the public health system; six tertiary adult oncology centers receive national referrals for radiotherapy, intensive chemotherapy, specialist surgery, and bone marrow transplant, while the remaining regional centers provide less complex chemotherapy and supportive care. All children under the age of 15, and some older teenagers, have their cancer care coordinated by a specialist multidisciplinary team based in one of New Zealand's two specialist pediatric cancer units. There are no distinct AYA cancer units and the decision on whether, for example, a 16-year-old adolescent with a high suspicion of cancer is referred to a pediatric or adult unit is determined on an ad hoc basis.

In the early 2000s a rapidly emerging and compelling body of international literature had identified a lack of progress in survival improvements for AYAs relative to other age groups and it was increasingly apparent that neither the traditional adult medical-based model or pediatric family-based model of cancer care were achieving optimal outcomes for this “lost tribe.”^1–3 At the same time as countries such as the United States, Canada, Australia, and the United Kingdom were establishing nationally organized cancer programs to address the unique needs of AYAs,^4–7 New Zealand clinicians set out to improve cure rates, entry onto clinical trials, and psychosocial care for their AYA patients. ⁸ This culminated in the development and national implementation of the AYA Cancer Service Specifications in 2009. ⁹ The AYA Service Specifications established specialist AYA cancer multidisciplinary teams within the six regional cancer centers, which included representatives from adult and pediatric oncology and hematology. AYA key workers were appointed to case-manage the care needs of AYA cancer patients and their families.

The 2009 AYA Service Specifications defined New Zealand AYA as 12–24 years, although it was acknowledged that some flexibility would be needed to ensure that the cancer care provided would best meet the unique treatment and psychosocial needs of the patient. ⁹ New Zealand's definition of AYA for service delivery purposes is similar to the 13–24 year Teenager and Young Adult age range used in the United Kingdom, ¹⁰ the 15–24 year range largely favored elsewhere in Europe,^11–13 and the 15–25 years in Australia's national service framework. ¹⁴ However, it is a narrower definition than the 15–29 years widely adopted in epidemiological studies,^15–20 or the 39 year upper age limit favored by the United States National Cancer Institute and LIVESTRONG.^21–23 Applying the 12–24 year age range, an average of 180 AYA were diagnosed in New Zealand on an annual basis between 2000 and 2009. Figure 1 highlights the geographical challenges that this presents with many AYA potentially travelling considerable distances to receive some, if not all, of their treatment at one of the six regional cancer centers or two specialist children's cancer units.

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FIG. 1.

Average annual number of AYA (12–24 years) diagnosed with cancer in New Zealand between 2000 and 2009 by AYA regional cancer center.

In 2012 the Ministry of Health established a national AYA Advisory Group to oversee a process to evaluate the effectiveness of existing AYA cancer services and provide recommendations for the future. During this review it became evident that there was little objective data pertaining to the current cancer burden among AYA and this analysis was commissioned to determine cancer incidence and survival for AYA, including comparisons with international benchmarks and within-group comparisons by age, sex, and ethnicity. New Zealand has a unique cultural and ethnic mix of peoples of Maori, Pacific, and European origin, and as such we have unique patterns of cancer in our population. There are known disparities in cancer survival in the adult population, with Maori and Pacific Island peoples having significantly worse outcomes. ²⁴ However, a recent analysis had shown comparable survival according to ethnicity for childhood cancer. ²⁵ This study sought to determine whether ethnic survival disparities existed for the AYA population once differences in the spectrum of cancers diagnosed had been accounted for.

Methods

Results

Discussion

The overall incidence of cancer in the New Zealand AYA population are comparable to those reported from other high-income countries.^12,35–38 The distinct age-related pattern of cancer in the 15–19 compared with the 20–24 year age groups represents the transition from the pediatric spectrum of disease into that seen in adults and serves to highlight the wide range of cancers that affect the AYA population. ³⁹ There were no unusual or unexpected differences in incidence by sex observed. The predominance of melanoma in New Zealand females is similar to that seen in Australia and the finding of increased risk for male AYA of developing ALL, non-Hodgkin lymphoma and gonadal germ cell tumors has been observed in other populations.^35–38

There were many notable significant ethnic differences in cancer incidence for AYA by diagnostic group. Melanoma was the most common cancer overall among 15–24 year olds, yet the incidence of melanoma among Maori and Pacific peoples was the lowest of any of the specified AYA diagnostic groups. Pacific AYA had a significantly higher incidence of leukemia compared to non-Maori/non-Pacific peoples. This, combined with the finding that Pacific children had the highest incidence of leukemia of the three prioritized ethnic groups in the same time period, ²⁶ suggests that the incidence differences may arise from a biological predisposition to leukemia among young Pacific people, which warrants further investigation. Among Maori, bone tumors were significantly more common, a novel finding in the New Zealand AYA population and of particular concern given survival outcomes for bone tumors were the poorest of any diagnostic group. Another unique and notable observation in this age group was the high frequency of gastric cancer among Maori AYA. This likely represents the known population-based familial association between gastric cancer and mutations in the E-cadherin gene. ⁴⁰ Such cases were most likely diagnosed as a result of the targeted screening program that exists for those identified as potential carriers of this gene mutation.

In comparison with other published AYA survival, New Zealand's overall 5-year relative survival for the 15–24 year age group of 80.6% was strikingly lower than the 5-year relative survival of 87% reported by the EUROCARE consortium for the 2000–2002 period and the 5-year observed survival of 85% reported by Canada for the 2001–2005 period.^13,36 It is in the adolescent rather than the young adult population in which these disparities are most evident. New Zealand cancer survival for those aged 15–19 years (75.1%) was significantly lower than the 81.8% survival reported by the U.S. SEER database for 2002–2008 and 81% reported by Canada for 2001–2005.^35,41 While survival for Hodgkin lymphomas, germ cell tumors, melanomas, and thyroid carcinoma, all at above 90%, appear on a par with international benchmarks,^{12,13,36,41,42} there is evidence to suggest that survival for adolescents diagnosed with malignant bone tumors, soft tissue sarcomas, and CNS tumors was poorer than has been achieved in the United States and Canada within a similar time period.^35,41 In addition, New Zealand adolescent ALL survival of 57.6% was considerably lower than the 75.9% survival achieved for adolescents enrolled on Children's Oncology Group (COG) clinical trials at this time, ⁴³ highlighting the importance of improving access to clinical trials for those adolescents not receiving treatment at either of New Zealand's COG-affiliated pediatric centers.^44,45

Of particular concern is the clear evidence of survival disparities according to ethnicity, with 5-year relative survival for AYA 13%–15% lower for Pacific peoples and Maori than for non-Maori/non-Pacific peoples. Survival disparities have been identified for other AYA minority populations but the reasons for these disparities are not yet well understood.^46–50 As comparisons by AYA diagnostic group provided evidence of poorer survival for Maori with leukemia, future studies should examine whether there is ethnic variation in the frequencies of cytogenetic abnormalities which are associated with an unfavorable prognosis, as has been identified in the United States. Similarly, the higher incidence of bone tumors for Maori begs the question of whether ethnic differences in tumor biology might contribute to the particularly poor survival outcomes that were identified for this group. The finding that there were no ethnic survival disparities in New Zealand's child population during the same time period suggests that comparable survival for AYA can be achieved, ²⁵ and that improvements to the AYA model of care, such as ensuring access to culturally appropriate health services, will be integral to improving survival outcomes for Maori and Pacific patients.

There are many factors that are known to impact AYA cancer survival, which were outside the scope of this study, and unexamined variables such as disease staging at presentation, duration between symptom onset and diagnosis, clinical trial participation, patient socioeconomic status, and treatment adherence may have contributed to the survival disparities that were identified.^1,21,47 Given that there are only a small number of tertiary centers with the resources to provide treatment for complex tumors in New Zealand, it is possible that those AYA who had to travel further for treatment, who were treated in multiple centers, or who received treatment in a center less experienced with the patient's particular disease had poorer survival outcomes. Future AYA survival analyses should utilize the recent improvements made by the NZCR in the collection of disease staging information and the standardization of data items collected by the AYA key workers in their respective centers.

An additional study limitation is the use of the prioritized ethnicity classification system, which goes against the principle of self-determination for the high proportion of New Zealand's younger population who identify with more than one ethnic group. Prioritized ethnicity has been shown to considerably understate the population count for Pacific peoples, with more than 20% of AYA who identified with a Pacific ethnic group in the 2006 census classified as Maori according to the prioritized system. ⁵² In addition, the combining of diverse ethnic groups, such as the absorption of Asian prioritized ethnicity into non-Maori/non-Pacific peoples, has potentially masked some ethnic incidence and survival differences that did exist in New Zealand during the study period.

On average, only 161 AYA aged 15–24 were diagnosed with cancer each year between 2000 and 2009 and for some specific cancers, such as osteosarcoma and Ewing tumors, the numbers were in the single digits. The rarity and wide spectrum of AYA cancers highlight the enormous challenges that New Zealand faces with regards to delivering high-quality, age-appropriate AYA cancer services across the country and also presents us with considerable challenges in the reporting of our data. The small number of AYA diagnosed with cancer, even over a 10-year period, results in wide CIs and makes it difficult to make meaningful comparisons by age group, sex, and ethnicity at an AYA diagnostic group or subgroup level. We must therefore strike a balance between interpreting our findings cautiously and the potential harm in not acting until we have improved the precision of our statistical estimates by accumulating several more years of cases. For example, this study identified that 5-year relative survival for Maori with leukemia was 24% lower than survival for non-Maori/non-Pacific peoples. Although this survival difference was not statistically significant, it would be advisable for researchers and AYA service providers to proceed on the assumption that there is a survival gap for Maori with leukemia and to commence research and initiatives that target this group.

As a wider issue, while a key original aim for this analysis was to compare New Zealand AYA cancer incidence and survival to that reported by other high-income countries we found that there were significant barriers to making meaningful cross-country comparisons. This was due to differences in the statistical methodologies between studies and the lack of a universally adopted AYA age range or classification system for AYA cancers. A universally adopted AYA cancer classification scheme and international consensus for AYA age groupings for use in study reporting, as was successfully implemented for childhood cancer in the 1980s, ⁵³ would encourage greater research collaboration and greatly assist in formulating etiologic hypotheses, monitoring survival improvements, and identifying international best practice to improve AYA cancer outcomes.

Conclusion

This is the first time that incidence and survival data pertaining specifically to AYA cancers in New Zealand has been published. It has highlighted the wide spectrum of cancers that we can expect to see among New Zealand's small AYA population and provided definitive patient numbers to inform decision making around national AYA cancer services. The survival analysis has shown New Zealand achieves excellent survival outcomes for many common AYA cancers such as lymphomas, germ cell tumors, melanomas, and thyroid carcinomas and has also identified some specific cancers, namely bone and soft tissue sarcomas, CNS tumors, and adolescent ALL, where the overall survival does not currently appear to meet international benchmarks. In addition, comparisons according to age and ethnicity have provided clear evidence of the existence of survival inequalities for adolescents when compared to our pediatric and young adults patients and for our Maori and Pacific AYA compared with those of other ethnicities.

Following the completion of the incidence and survival analysis, and an AYA Patient Experience and Service Evaluation that had been conducted concurrently, the AYA Advisory Group made their recommendations to the Ministry of Health regarding the future delivery of AYA cancer services. In December 2013, the Ministry of Health acknowledged that New Zealand can and should be doing better for our young people and announced increased funding for AYA cancer services and the establishment of the AYA Cancer Network Aotearoa. Using a model based on the National Child Cancer Network, which had been successfully implemented in 2012, the AYA Cancer Network Aotearoa brings together health professionals and support providers from many disciplines and organizations with a shared aim to ensure that all AYAs diagnosed with cancer, regardless of geography, have equitable access to high quality medical and psychosocial care. While New Zealand's small cancer workforce and low annual AYA cancer patient numbers do provide us with considerable challenges, they also, by necessity, encourage close collaboration across services and presents us with unique opportunities to develop innovative solutions that can be implemented nationally in a relatively short time period. By 2017 the AYA Cancer Network Aotearoa will have produced a comprehensive national strategy for AYA cancer care to address these health inequalities and improve the outcomes for New Zealand AYA diagnosed with cancer.