Abstract
Background
Epidemiological data on cancers in adolescents and young adults (AYAs; aged 15-39 years) suggest rising incidence of AYA cancers alongside international differences in incidence and survival. We compared incidence, survival and trends over time for cancers in AYAs in the European Union (EU) and the United States.
Materials and methods
We used the EUROCARE-6 database and the US SEER program. We calculated crude incidence rates (IRs) over the years 2006-2013. We calculated 5-year relative survival (RS) in the follow-up period 2010-2014 using the period approach based on cases diagnosed in 2006-2013. We analysed IR and RS changes for the years 2000-2013.
Results
Overall, 5-year RS was ∼84% in the EU and United States and improved over time in both regions. Compared with US patients, AYA cancer patients in the EU had lower survival for central nervous system (CNS) tumours and malignant melanoma but higher survival for leukaemias, testicular germ cell tumours (TGCTs), and cervical cancer. Both in the EU and the United States, major improvements in 5-year RS were observed for leukaemias, CNS tumours, lymphomas, and breast cancers. Cancer in AYAs corresponds to ∼5% of all new cancers diagnosed in the EU and United States. The IR increased for all cancers in AYAs in both regions, with the biggest increase due to thyroid cancers, TGCTs, and colorectal cancer.
Conclusions
Our results show survival improvements for most types of AYA cancers and underline the need for further international efforts to increase survival for tumours (e.g. CNS tumours) for which 5-year RS remains <60%. Furthermore, the increasing incidence underscores the importance of giving priority to cancer prevention.
Key words: adolescents and young adults, incidence, population-based cancer registries, survival
Highlights
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Approximately 80 000 new cancer cases are diagnosed every year in AYAs in the EU and United States.
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IRs increased for all cancers in AYAs in the EU and United States.
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Five-year RS for AYA cancers overall was 84% in the EU and United States.
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European RS for ALL, AML, and CNS tumours was <60%; leukaemias overall had 70% RS.
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RS improved from 2000 to 2013 by 4.6% in the EU and 2.7% in the United States.
Introduction
Cancers in adolescents and young adults (AYAs; aged 15-39 years) are rare,1 but recent studies suggest a rising incidence of many cancers in AYAs, alongside international differences.2, 3, 4, 5 Separate studies from the Europe (EU) and the United States have reported lower survival in AYA cancer patients than in children and adults.6, 7, 8, 9, 10, 11, 12 Furthermore, only modest improvements in survival for AYA cancer patients over recent decades have been reported, and this has been attributed to factors including reduced participation in clinical trials, lack of specialised centres for AYA cancer, and limited understanding of AYA tumour biology.13
The United States has been at the forefront of AYA-focused initiatives, including dedicated research programs, clinical trials, and specialised care centres,12 while the EU has generally lagged behind, although recent efforts are closing this gap.13 Comparing outcomes between these regions is therefore important to identify effective strategies and areas needing improvement.
However, such comparisons are challenging due to the considerable heterogeneity within both the United States and Europe. Differences in population genetics, lifestyle factors, socioeconomic status (SES), health care systems, and public health policies vary widely across states and countries, affecting cancer incidence and outcomes. This diversity requires careful interpretation but also provides a rich context to understand factors influencing AYA cancer survival.
Differences in cancer incidence may reflect variations in risk factor distributions, including environmental exposures and genetic predispositions, which are particularly relevant in the ethnically diverse US population. Survival disparities are often linked to differences in access to health care services, impacting stage at diagnosis, and treatment access and availability. In the United States, unequal access to care due to socioeconomic and insurance-related factors is a notable concern.14,15 Despite their differences, the United States and the EU share many characteristics as Western countries, making comparisons feasible. Furthermore, data availability from the United States provides a useful benchmark for evaluating AYA cancer outcomes.
Our study aims to directly compare incidence, survival, and trends over time for AYA cancer patients in the EU and the United States. Findings from this comparison may identify persistent or new inequalities, supporting international collaborative efforts.
Materials and methods
Data collection
For the EU, we used the EUROCARE-6 database, which includes patients diagnosed with primary cancer in 2000-2013 and followed up until 2014 from 95 population-based cancer registries (CRs) across 27 European countries.
For the United States, we used data from 17 CRs from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) program, selecting the same years of diagnosis and follow-up as the EUROCARE-6 cohort. Data quality indicators are summarised in Supplementary Table S1, available at https://doi.org/10.1016/j.esmorw.2026.100745.
In our analyses, we included only cancers with malignant behaviour code in the International Classification of Diseases for Oncology, Third Edition, First Revision (ICD-O3-1). We excluded nonmelanoma skin cancers and pilocytic astrocytoma. If two or more cancers were diagnosed in a patient within the study period, we included all of them in both survival and incidence analyses. Analyses were carried out for all cancers, and for the most common cancers in AYAs were grouped into 12 diagnostic categories adapted from Barr et al.16
Incidence and survival
We calculated crude incidence rates (IRs) per 100 000 individuals per year in the population, over the period 2006-2013, and estimated incidence as the number of new cancer cases in 2006-2013 divided by the corresponding total person-years in the general population, with associated 95% confidence intervals (CIs).
We calculated 5-year relative survival (RS) in the follow-up period 2010-2014 using the period approach based on cases diagnosed in 2006-2013 who were followed up for vital status up to 31 December 2014.17 We estimated RS, the ratio of observed to expected survival in the general population of the same areas, as defined using life tables. In both the EU and United States, life tables are matched by age, sex, and calendar year; in the EU, they are also matched by country, whereas in the United States, they are also matched by race. We estimated RS using the Ederer II method and calculated 95% CIs.18
We also calculated 2010-2014 conditional survival (CS), defined as the ratio of 5-year RS to 1-year RS. This measure was used to determine whether the differences in 5-year RS between the EU and the United States persisted beyond the first year after diagnosis, or if they were primarily driven by early mortality. Early mortality likely reflects cases that are metastatic, advanced, or clinically aggressive, especially given the lack of available stage information.
We calculated absolute differences in IR and RS between the EU and the United States and considered differences to be statistically significant if the CIs of the estimates did not overlap.
Incidence and survival time trends (diagnosis period 2000-2013)
To be consistent between incidence and survival trends, we selected the same two periods of diagnosis: 2006-2013 and 2000-2006.
We estimated changes in IR using the incidence rate ratio (IRR), i.e. the ratio between the IR of the two incidence periods. We used the F-interval P values to evaluate statistically significant IRR differences over time.19
We analysed 5-year RS changes at three follow-up points corresponding to the same diagnosis years as the incidence trends: 2004-2006 (diagnosis period 2000-2006) and 2010-2014 (diagnosis period 2006-2013). To describe RS changes, we calculated the percentage differences between RS in 2010-2014 and 2004-2006. We considered the survival trend to be statistically significant if the 95% CIs of RS estimates from these two follow-up periods did not overlap.
In the EU, 69 of 95 CRs provided data covering at least the period of diagnosis 2001-2010, which contributed to the survival and incidence trend analyses. In the United States, all 17 CRs contributed to the time trends.
All analyses were computed using SEER∗Stat Software version 8.4.4.
Results
We analysed 420 877 and 151 671 AYAs with cancers in the EU and the United States, respectively, during the diagnostic period 2006-2013. Quality indicators were similar in both continents (Supplementary Table S1, available at https://doi.org/10.1016/j.esmorw.2026.100745).
Incidence
Overall, the IR per 100 000 was 60 in the EU and 66 in the United States (Table 1). Approximately 80 000 and 74 000 new cancer cases are diagnosed every year in AYAs in the EU and United States, corresponding to 4% and 5% of all new cancer diagnoses in the EU and the United States, respectively (Supplementary Figure S1A, available at https://doi.org/10.1016/j.esmorw.2026.100745). The cancer case mix across AYA age groups was similar in the EU and the United States (Supplementary Figure S1B, available at https://doi.org/10.1016/j.esmorw.2026.100745). In the United States , the most common cancers were breast (BC) and thyroid carcinoma (TC) (IR ∼10) followed by lymphomas, malignant melanoma (MM) and testicular germ cell tumours (TGCTs) (IR = 8.7 and 5, respectively). In the EU, BC was the most common (IR = 9.6) followed by MM, lymphomas, TGCTs (IR ∼7 each) and TCs (IR = 5.0). The other tumours had an IR ranging from ∼4 per 100 000 (cervical cancer) to <1 per 100 000 (bone sarcomas and ovarian germ cell tumours) in both regions.
Table 1.
Crude incidence rate by cancer type in European and United States AYAs (aged 15-39 years) in 2006-2013
| Europe |
United States |
Europe versus United States |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| N | IR | 95% CI | N | IR | 95% CI | IR difference | |||
| Leukaemias and related disorders | 19 756 | 2.8 | 2.8 | 2.9 | 7564 | 3.3 | 3.2 | 3.4 | −0.5a |
| Acute lymphoblastic leukaemia | 4604 | 0.7 | 0.6 | 0.7 | 2277 | 1.0 | 1.0 | 1.0 | −0.3a |
| Acute myeloid leukaemia | 6586 | 0.9 | 0.9 | 1.0 | 2976 | 1.3 | 1.2 | 1.3 | −0.4a |
| Chronic myeloid leukaemia | 2870 | 0.4 | 0.4 | 0.4 | 1527 | 0.7 | 0.6 | 0.7 | −0.3a |
| Lymphomas | 49 304 | 7.0 | 7.0 | 7.1 | 18 045 | 7.9 | 7.7 | 8.0 | −0.9a |
| NHL | 19 552 | 2.8 | 2.8 | 2.8 | 8656 | 3.8 | 3.7 | 3.8 | −1.0a |
| Lymphoblastic | 669 | 0.1 | 0.1 | 0.1 | 426 | 0.2 | 0.2 | 0.2 | −0.1a |
| Burkitt | 1169 | 0.2 | 0.2 | 0.2 | 686 | 0.3 | 0.3 | 0.3 | −0.1a |
| Diffuse large B-cell | 6683 | 1.0 | 0.9 | 1.0 | 3417 | 1.5 | 1.4 | 1.5 | −0.5a |
| Primary mediastinal large B-cell | 790 | 0.1 | 0.1 | 0.1 | 240 | 0.1 | 0.1 | 0.1 | −0.0 |
| Anaplastic T- and null-cell | 733 | 0.1 | 0.1 | 0.1 | 340 | 0.1 | 0.1 | 0.2 | −0.0 |
| Follicular | 3001 | 0.4 | 0.4 | 0.4 | 1051 | 0.5 | 0.4 | 0.5 | −0.1 |
| NK/T-cell | 1014 | 0.1 | 0.1 | 0.2 | 455 | 0.2 | 0.2 | 0.2 | −0.1 |
| MALT | 1232 | 0.2 | 0.2 | 0.2 | 557 | 0.2 | 0.2 | 0.3 | −0.0 |
| Other NHL, NOS | 3144 | 0.4 | 0.4 | 0.5 | 693 | 0.3 | 0.3 | 0.3 | 0.1a |
| Hodgkin lymphoma | 26 692 | 3.8 | 3.8 | 3.9 | 8330 | 3.6 | 3.5 | 3.7 | 0.2a |
| CNS and other intracranial and intraspinal neoplasms | 19 602 | 2.8 | 2.8 | 2.8 | 5947 | 2.6 | 2.5 | 2.7 | 0.2a |
| Bone sarcomas | 5694 | 0.8 | 0.8 | 0.8 | 1985 | 0.9 | 0.8 | 0.9 | −0.1 |
| Osteosarcoma | 1983 | 0.3 | 0.3 | 0.3 | 820 | 0.4 | 0.3 | 0.4 | −0.1 |
| Chondrosarcoma | 1352 | 0.2 | 0.2 | 0.2 | 451 | 0.2 | 0.2 | 0.2 | −0.0 |
| Ewing family of tumours of bone | 1401 | 0.2 | 0.2 | 0.2 | 403 | 0.2 | 0.2 | 0.2 | −0.0 |
| STSs | 9393 | 1.3 | 1.3 | 1.4 | 4177 | 1.8 | 1.8 | 1.9 | −0.5a |
| Liposarcoma | 1480 | 0.2 | 0.2 | 0.2 | 559 | 0.2 | 0.2 | 0.3 | −0.0 |
| Leiomyosarcoma | 1162 | 0.2 | 0.2 | 0.2 | 434 | 0.2 | 0.2 | 0.2 | −0.0 |
| Synovial sarcoma | 1154 | 0.2 | 0.2 | 0.2 | 494 | 0.2 | 0.2 | 0.2 | −0.0 |
| Rhabdomyosarcoma | 816 | 0.1 | 0.1 | 0.1 | 350 | 0.2 | 0.1 | 0.2 | −0.1 |
| Germ cell and trophoblastic tumours of testis | 47 722 | 6.8 | 6.7 | 6.9 | 12 289 | 5.4 | 5.3 | 5.4 | 1.4a |
| Germ cell and trophoblastic tumours of ovary | 1683 | 0.2 | 0.2 | 0.3 | 822 | 0.4 | 0.3 | 0.4 | −0.2 |
| Melanoma—malignant | 49 939 | 7.1 | 7.1 | 7.2 | 15 570 | 6.8 | 6.7 | 6.9 | 0.3a |
| TC | 36 329 | 5.2 | 5.1 | 5.2 | 22 333 | 9.7 | 9.6 | 9.9 | −4.5a |
| Carcinoma of colon-rectum (excl appendix) | 15 608 | 2.2 | 2.2 | 2.3 | 7083 | 3.1 | 3.0 | 3.2 | −0.9a |
| Carcinoma of breast | 67 119 | 9.6 | 9.5 | 9.6 | 21 723 | 9.5 | 9.3 | 9.6 | 0.1 |
| Carcinoma of uterine cervix | 28 160 | 4.0 | 4.0 | 4.1 | 6609 | 2.9 | 2.8 | 2.9 | 1.1a |
| All cancers | 420 877 | 60.1 | 59.9 | 60.2 | 151 671 | 66 | 65.7 | 66.4 | −5.9a |
Crude incidence rate (IR, per 100 000) by cancer type and all cancers in European and American AYAs (aged 15-39 years), in 2006-2013, with number of cases (N) and 95% CIs. IR differences between Europe and United States are also reported.
AYAs, adolescents and young adults; CIs, confidence intervals; CNS, central nervous system; excl, excluding; MALT, mucosa-associated lymphoid tissue; NHL, non-Hodgkin lymphoma; NOS, not otherwise specified; NK, natural killer; STSs, soft tissue sarcomas; TC, thyroid carcinoma.
Statistically significant difference.
Compared with the United States, in the EU, IR was lower for leukaemias, lymphomas [mainly non-Hodgkin lymphoma (NHL)], soft tissue sarcomas (STSs), carcinoma of colon-rectum, and TC. IR was higher for central nervous system (CNS) tumours, TGCTs, MM, and cervical cancer.
Survival
Five-year RS in AYA cancers overall was 83.4% and 84.1% in the EU and the United States, respectively (Table 2), and survival was high (>70%) for most cancers in the EU and United States. In both regions, testicular and ovarian germ cell tumours, TC, and MM had the highest survival (5-year RS >90%), with BC, cervical cancer, and lymphomas having 5-year RS >80%. For leukaemias, STSs, bone sarcomas, colon cancer, and CNS tumours, 5-year RS ranged from 60% to 70%.
Table 2.
Five-year RS by cancer type in European and the United States AYAs (aged 15-39 years)
| Europe |
United States |
Europe versus United States |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| N | RS | 95% CI | N | RS | 95% CI | RS difference | |||
| Leukaemias and related disorders | 9810 | 72.7% | 71.8% | 73.6% | 3746 | 67.7% | 66.1% | 69.2% | 5.0%a |
| Acute lymphoblastic leukaemia | 2282 | 61.3% | 59.2% | 63.3% | 1136 | 59.8% | 56.8% | 62.7% | 1.5% |
| Acute myeloid leukaemia | 3271 | 58.1% | 56.3% | 59.9% | 1483 | 57.3% | 54.7% | 59.8% | 0.8% |
| Chronic myeloid leukaemia | 1428 | 92.8% | 91.3% | 94.1% | 762 | 89.7% | 87.2% | 91.7% | 3.1% |
| Lymphomas | 24 730 | 89.4% | 89.0% | 89.8% | 8948 | 88.3% | 87.6% | 89.0% | 1.1% |
| NHL | 9851 | 83.8% | 83.0% | 84.5% | 4312 | 83.0% | 81.9% | 84.2% | 0.8% |
| Lymphoblastic | 340 | 63.1% | 57.6% | 68.1% | 212 | 69.6% | 62.7% | 75.5% | −6.5% |
| Burkitt | 613 | 75.7% | 72.0% | 79.0% | 346 | 72.0% | 66.7% | 76.6% | 3.7% |
| Diffuse large B-cell | 3385 | 82.3% | 80.9% | 83.6% | 1724 | 80.8% | 78.8% | 82.7% | 1.5% |
| Primary mediastinal large B-cell | 403 | 90.6% | 87.3% | 93.0% | 119 | 89.3% | 81.8% | 93.8% | 1.3% |
| Anaplastic T- and null-cell | 366 | 82.8% | 78.3% | 86.5% | 171 | 83.3% | 76.5% | 88.3% | −0.5% |
| Follicular | 1533 | 94.7% | 93.4% | 95.8% | 524 | 94.9% | 92.4% | 96.6% | −0.2% |
| NK/T-cell | 510 | 60.1% | 55.6% | 64.4% | 224 | 53.9% | 47.0% | 60.4% | 6.2% |
| MALT | 646 | 95.0% | 92.9% | 96.5% | 278 | 97.6% | 94.6% | 99.0% | −2.6% |
| Other NHL, NOS | 1540 | 80.9% | 78.7% | 82.9% | 334 | 80.0% | 75.2% | 83.9% | 0.9% |
| Hodgkin lymphoma | 13 425 | 94.5% | 94.1% | 94.9% | 4157 | 94.9% | 94.1% | 95.6% | −0.4% |
| CNS and other intracranial and intraspinal neoplasms | 9631 | 61.1% | 60.1% | 62.1% | 2955 | 67.5% | 65.8% | 69.2% | −6.4%a |
| Bone sarcomas | 2824 | 69.0% | 67.2% | 70.7% | 977 | 70.5% | 67.5% | 73.3% | −1.5% |
| Osteosarcoma | 987 | 64.2% | 61.1% | 67.2% | 407 | 61.5% | 56.6% | 66.1% | 2.7% |
| Chondrosarcoma | 678 | 86.6% | 83.7% | 89.0% | 226 | 88.8% | 83.7% | 92.4% | −2.2% |
| Ewing family of tumours of bone | 710 | 51.1% | 47.2% | 54.8% | 197 | 56.9% | 49.6% | 63.6% | −5.8% |
| STSs | 4664 | 68.0% | 66.6% | 69.4% | 2073 | 68.8% | 66.7% | 70.8% | −0.8% |
| Liposarcoma | 737 | 85.6% | 82.7% | 88.0% | 280 | 85.5% | 80.6% | 89.2% | 0.1% |
| Leiomyosarcoma | 579 | 73.8% | 69.9% | 77.3% | 217 | 61.8% | 55.0% | 67.9% | 12.0%a |
| Synovial sarcoma | 580 | 64.6% | 60.4% | 68.4% | 239 | 67.0% | 60.4% | 72.7% | −2.4% |
| Rhabdomyosarcoma | 401 | 40.9% | 36.0% | 45.7% | 173 | 43.4% | 35.8% | 50.9% | −2.5% |
| Germ cell and trophoblastic tumours of testis | 23 973 | 96.7% | 96.5% | 97.0% | 6074 | 95.6% | 95.0% | 96.2% | 1.1%a |
| Germ cell and trophoblastic tumours of ovary | 851 | 95.5% | 93.8% | 96.8% | 419 | 94.5% | 91.7% | 96.4% | 1.0% |
| Melanoma—malignant | 25 199 | 93.3% | 92.9% | 93.6% | 7586 | 94.8% | 94.2% | 95.3% | −1.5%a |
| TC | 18 857 | 99.5% | 99.3% | 99.6% | 11 119 | 99.7% | 99.5% | 99.8% | −0.2% |
| Carcinoma of colon-rectum (excl appendix) | 7749 | 64.4% | 63.3% | 65.5% | 3454 | 66.7% | 65.1% | 68.3% | −2.3% |
| Carcinoma of breast | 33 506 | 85.8% | 85.4% | 86.1% | 10 597 | 86.2% | 85.5% | 86.8% | −0.4% |
| Carcinoma of uterine cervix | 14 013 | 85.2% | 84.5% | 85.8% | 3286 | 80.7% | 79.2% | 82.0% | 4.5%a |
| All cancers | 209 100 | 83.40% | 83.20% | 83.50% | 74 305 | 84.10% | 83.90% | 84.40% | −0.7%a |
Five-year RS by cancer type and for all cancers in European and American AYAs (aged 15-39 years), with number of cases (N) and 95% CIs. Follow-up period 2010-2014, based on cases diagnosed in 2006-2013. RS differences are also reported.
AYAs, adolescents and young adults; CIs, confidence intervals; CNS, central nervous system; excl, excluding; MALT, mucosa-associated lymphoid tissue; NHL, non-Hodgkin lymphoma; NOS, not otherwise specified; NK, natural killer; RS, relative survival; STSs, soft tissue sarcomas; TC, thyroid carcinoma.
Statistically significant difference.
Compared with the United States, the EU had lower 5-year RS for CNS tumours (−6.4%) and MM (−1.5%) but higher 5-year RS for leukaemias (+5.0%), TGCTs (+1.1%) and cervical cancer (+4.5%). For STS, 5-year RS was lower in EU for synovial sarcoma and rhabdomyosarcoma (∼−2.5%; not significant) but higher for leiomyosarcoma (+12%).
For most AYA cancers (i.e. leukaemias, lymphomas, CNS tumours, bone sarcomas, TGCTs, MM, and all carcinomas), survival differences decreased when CS was analysed (Supplementary Table S2, available at https://doi.org/10.1016/j.esmorw.2026.100745).
Incidence time trends
Figure 1 includes cancers that had different incidence trends between the EU and the United States. Incidence trends for each individual cancer in the EU and the United States are reported in Supplementary Table S3, available at https://doi.org/10.1016/j.esmorw.2026.100745. The IR increased for all cancers in AYAs in both regions, from 53.5 to 58.4 per 100 000 in the EU and 63.9 to 66.0 per 100 000 in the US (Figure 1), but individual tumours were affected differently (Supplementary Table S3, available at https://doi.org/10.1016/j.esmorw.2026.100745).
Figure 1.
Incidence trends (2000-2006 versus 2006-2013) for all cancers and selected cancer types among AYAs (aged 15-39 years) in Europe and the United States. Only cancers with differing trends between regions are shown. AYAs, adolescents and young adults; NK, natural killer.
In both the EU and the United States, the largest increases in IR over time were found for TC (IRR 1.4 in EU and 1.3 in United States), followed by TGCTs (IRR 1.2 in EU and 1.1 in United States) and colorectal cancer (IRR 1.1 in EU and 1.1 in United States). IR in both the EU and the United States was stable for CNS tumours, bone sarcomas, and STSs. For ovarian germ cell tumours, IR was stable in the United States and increased in the EU.
For MM, cervical cancer, BC, and lymphomas, IRs decreased over time in the United States (IRR 0.9, 0.9, 1.0 and 1.0, respectively), whereas they increased in the EU (IRR 1.2, 1.1, 1.1, and 1.0, respectively) (Figure 1). In the United States, IR increased for leukaemias overall and by subtype [acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML)], whereas in the EU, IRs remained stable (IRR ∼1) (Figure 1).
Survival time trends
Figure 2 includes cancers that had different RS trends between the EU and the United States. RS trends for each individual tumour in the EU and the United States are in Supplementary Table S4, available at https://doi.org/10.1016/j.esmorw.2026.100745. Overall, 5-year RS improved between 2000 and 2013 both in the EU and the United States, by 4.6% and 2.7%, respectively (Figure 2) but with differences by individual tumour type (Supplementary Table S4, available at https://doi.org/10.1016/j.esmorw.2026.100745). Both in the EU and the United States, major improvements in 5-year RS were found for leukaemias overall (+9.0% in the EU and the United States) and by subtype, CNS tumours (+4.3% and +4.9%, respectively), lymphomas overall (+3.9% and +4.2%), and by subtype, and BC (+3.0% and +2.4%).
Figure 2.
Five-year RS trends for all cancers and selected cancer types among AYAs (aged 15-39 years) in Europe and the United States, comparing 2004-2006 (diagnosed 2000-2006) and 2010-2014 (diagnosed 2006-2013). Only cancers with differing trends between regions are shown. AYAs, adolescents and young adults; excl, excluding; RS, relative survival.
Survival trends for TC, TGCTs, Ewing bone tumours, osteosarcoma, and STSs were stable in both the EU and the United States. Survival for chondrosarcoma, cervical and colorectal carcinomas, and MM improved significantly in the EU (+8.4%, +4.1%, +3.0%, +2.9%, respectively) while remaining stable in the United States (Figure 2).
Discussion
Our results show that survival improved over time (2000-2013) for AYA cancer patients in both the EU and the United States and that survival was similar in both regions with few exceptions. Compared with the United States, AYA cancer patients in the EU had lower survival for CNS tumours and MM but higher survival for leukaemias and cervical cancer.
Advances in surgical techniques, new targeted therapies, better prognostication and risk-adapted therapies might all have contributed to improvements in cancer survival we observed in AYAs. Furthermore, collaborative initiatives may also have contributed to improving outcomes in AYAs. In the United States, these initiatives included efforts to address low clinical trial enrolment among AYAs and efforts to improve access to AYA-specialized cancer centres.12 In the EU, in 2015, the Cancer in AYA Working Group was established to improve the standard of care for AYAs with cancer across the EU,13 and in 2024, a network of expertise focused on AYAs with cancers was also established to address AYA-specific challenges. Our data pre-dates implementation of these relevant European initiatives.
Our results confirmed clinically significant survival differences between the EU and the United States for leukaemia, CNS tumours, leiomyosarcoma, and carcinoma of the uterine cervix. Although survival differences for TGCTs and MM were statistically significant, they were only ∼1% and are unlikely to be clinically meaningful. However, although we observed a survival gap for European AYAs compared with US AYAs with CNS tumours and MM, the trend suggests that for MM, this survival gap is expected to narrow further in the near future.
Survival of AYAs with CNS tumours in the EU lags behind that in the United States despite advances in neuroimaging and neurosurgical techniques, the centralization of neurosurgical and neuro-oncology expertise, and multidisciplinary management. Furthermore, limited survival improvements do not appear sufficient to close the gap. However, survival differences decreased when CS was analysed (Supplementary Table S2, available at https://doi.org/10.1016/j.esmorw.2026.100745), supporting the idea that earlier diagnosis may also help explain the higher RS in the United States. Finally, for those CNS tumours that can only be diagnosed radiologically (e.g. meningiomas, diffuse intrinsic pontine glioma), we cannot exclude misdiagnoses in registration.20
The poorer survival of AYAs with cervical cancer in the United States may relate to differences in screening programs or screening delays and/or to more aggressive histologic subtypes in AYAs.12,21,22
Poorer survival of AYAs with hematologic cancers in the United States has been previously reported.23 The observed difference could be attributed to a greater collaboration between paediatric and medical oncologists in the EU, leading to a wider use of a paediatric treatment approach to AYAs than in the United States. Differences in CML may be due to different access to targeted treatments (tyrosine kinase inhibitors). Continuous Medicaid coverage is associated with survival benefits among AYAs diagnosed with blood cancers; however, fewer than half of Medicaid-insured patients had continuous coverage before diagnosis.14 Also, for sarcomas, it has been reported that AYAs with bone sarcoma and STS with public insurance had inferior survival compared with patients with private insurance.15
It should also be noted that, for some AYA cancers with significantly different survival between the EU and the United States, there was also a marked geographic variation in survival, at least within the EU. Among cancers with lower survival in the EU than in the United States, in Denmark and Germany, survival from MM was higher than in the United States.11 Among those with higher survival in the EU compared with the United States, survival from both TGCTs and cervical cancers was lower in Bulgaria, Latvia, and Poland compared with the United States.11 Within the EU, survival differences were attributed to early diagnosis, different access to care, and possible cancer misclassification.1
It has been reported that in the United States, AYAs who identified as a racial/ethnic minority, with a lower SES, and residing in rural areas had an increased hazard of death for several AYA cancers (e.g. haematological tumours, STSs, TGCTs).15,24, 25, 26 In the EUROCARE-6 and SEER databases, there is no information to assess racial (EUROCARE-6) and/or SES (SEER) impact on survival differences.
Another major finding of our study was that the increased incidence was mainly due to TC, TGCTs, and MM in the EU and to TC in the United States. Our results show a higher increase in TC incidence in the United States, which is consistent with greater levels of overdiagnosis in the United States than in the EU.26 The increased incidence of TGCTs is also in line with previous studies.27 The increase in MM incidence has been attributed to improvements in cancer detection methods and the spread of awareness campaigns in European countries. A study in the United States has already reported a decrease in MM IR in AYAs, whereas the situation is more heterogeneous in European countries.28, 29, 30, 31, 32 In general, risk factors differ widely across countries; thus, incidence trends observed for the EU overall may differ from those in individual countries.33
Our results also showed differences in incidence between the EU and the United States. Variations in cancer incidence across different populations may reflect different distributions of risk factors including lifestyle, access to health care, variations in the implementation of screening or vaccination programmes (e.g. cervical cancer), overdiagnosis as well as changes in cancer classification and misclassification due to registration problems. Compared with the United States, IR was lower in the EU for NHL, TC, and carcinoma of colon-rectum, whereas it was higher for TGCTs and cervical cancers.
The HIV/AIDS epidemic in the United States dramatically increased the incidence of NHL, while the EU did not experience a similar increase.23 Furthermore, the lower incidence of NHL not otherwise specified in the United States may suggest better classification there. However, the harmonization of different classifications, a reduced heterogeneity of health care in the EU, and the increasingly easy access to pathologic and molecular laboratories should progressively reduce the gap in the next few years.
The specific reasons for the higher incidence of colorectal cancer in the United States compared with the EU are not known. Possible explanations include the higher population levels of obesity and different levels of access to colonoscopy despite the lack of clear guidelines for colonoscopy in AYAs.34
Regarding TC, the different extent of overdiagnosis and different distribution of risk factors such as obesity may contribute to explaining the observed differences in IR.35, 36, 37
The higher incidence of TGCTs in the EU is well known but not well explained. Birth cohort effects and occupational, environmental, and maternal exposure to exogenous toxins might play a role.38 Some recent studies have explored cannabis use as a potential factor associated with an increased risk of certain TGCTs, but its role is not yet established and requires further investigation.39 Unfortunately, we did not have this information in our dataset.
Finally, the lower incidence of cervical cancers in the United States may be attributed to possible screening delays as it is also supported by the observed decrease in survival.12,21,22
Our study has several limitations. Notably, it lacks information on cancer stage, molecular characterization, and treatment details. Additionally, the higher cancer incidence observed in the United States may be influenced by factors such as lifestyle, health care access, and SES, which were not captured in this analysis. Another limitation is the relatively old diagnostic period and end of the follow-up. However, we used the period approach to estimate the most up-to-date 5-year RS based on the available data. Moreover, trends were analysed by comparing two aggregated periods rather than by joinpoint regression. This approach aligns with the study’s objective, which was to estimate the net change in incidence and survival between two predefined periods in the EU and the United States, rather than to describe the detailed shape of annual trend patterns. Aggregating years also enabled us to obtain more robust estimates for rare AYA cancers and their subtypes. Notably, published EUROCARE-6 analyses based on annual percentage changes reported conclusions that are consistent with our European trend findings.40
To estimate the expected number of new cases per year, we assumed a constant cancer incidence over time. Given the increasing trends observed in recent years, this assumption may be strong and could have resulted in a slight underestimation of the reported figures.
We also used crude IRs rather than age-standardized rates, which may introduce some bias due to differences in age structures within the 15-39 years age group over the study period and between Europe and the United States. However, the age distributions in this AYA population are relatively comparable between regions, with only minor differences, such as a slightly higher (but not statistically significant) proportion of individuals aged 35-39 years in Europe, whereas no differences in sex distribution are observed.41 Moreover, no standard population weights have been established specifically for this age range in cancer epidemiology.
As reported, another limitation is that survival varies within Europe due to differences in health care, socioeconomic factors, and treatment access, which may affect the overall results.
The strengths of this study include being the most up-to-date, unbiased real-world evidence on AYA cancers (the two datasets used are representative of the EU and US populations). To our knowledge, this is the first study to directly compare incidence and survival between the EU and the United States.
Our results, while reassuringly showing survival improvements for most types of AYA cancers, also underline the need for further international efforts to increase survival for ALL, AML, and CNS tumours, for which 5-year survival remains <60%. Furthermore, the increasing incidence underscores the importance of considering cancer prevention a priority.
Acknowledgements
EUROCARE-6 Working group: Austria: M. Hackl (National CR); Belgium: E. Van Eycken; N. Van Damme (National CR); Bulgaria: Z. Valerianova (National CR); Croatia: M. Sekerija (National CR); Cyprus: I. Gregoriou; A. Demetriou (National CR); Czechia: L. Dusek; D. Krejici (National CR); Denmark: H. Storm (National CR); Estonia: M. Mägi; K. Innos∗ (National CR); Finland: J. Pitkaniemi (National CR); France: M. Velten (Bas Rhin CR); X. Troussard (Basse Normandie, Haematological Malignancies CR); A. M. Bouvier; V. Jooste∗ (Burgundy, Digestive CR); N. Vigneron (Calvados, General CR); G. Launoy (Calvados, Digestive CR); S. Dabakuyo Yonli (Cote d’Or, Gynaecological (Breast) CR); M. Maynadie, A. Guilloteau (Cote d’Or, Haematological Malignancies CR); A. S. Woronoff (Doubs CR); J. B. Nousbaum (Finistere, Digestive CR); G. Coureau (Gironde, General CR); A. Monnereau∗ (Gironde, Haematological Malignancies CR); I. Baldi (Gironde, Central Nervous System CR); K. Hammas (Haut-Rhin CR); B. Tretarre (Herault CR); M. Colonna (Isere CR); S. Plouvier (Lille Area CR); T. D’Almeida (Limousin CR); F. Molinié; A. Cowppli-Bony (Loire-Atlantique/Vendée CR); S. Bara (Manche CR); A. Debreuve (Marne-Ardennes, Thyroid CR); G. Defossez (Poitou-Charentes CR); B. Lapôtre-Ledoux (Somme CR); S. Lamy; L. Daubisse-Marliac (Tarn CR); Germany: S. Luttmann; A. Eberle (Bremen CR); R. Stabenow [Common CR of four Federal States (Brandenburg, Mecklenburg-West Pomerania, Saxony-Anhalt, Thüringen)]; A. Nennecke; F. Peters (Hamburg CR); J. Kieschke (Lower Saxony CR); S. Zeissig (Rhineland-Palatinate CR); B. Holleczek (Saarland CR); A. Katalinic∗ (Schleswig-Holstein CR); Iceland: H. Birgisson (National CR); Ireland: D. Murray (National CR); Italy: G. Mazzoleni; F. Vittadello (Alto Adige CR); F. Cuccaro (Barletta-Andria-Trani CR); R. Galasso (Basilicata CR); G. Sampietro (Bergamo CR); S. Rosso (Biella CR); C. Gasparotti; G. Maifredi (Brescia CR); M. Ferrante; R. Ragusa (Catania-Messina-Enna CR); A. Sutera Sardo (Catanzaro CR); M. L. Gambino; M. Lanzoni (Province of Varese and Como CR); P. Ballotari; E. Giacomazzi (Cremona and Mantova CR); S. Ferretti (Ferrara CR); A. Caldarella; G. Manneschi (Firenze-Prato CR); G. Gatta∗; M. Sant∗; P. Baili∗; F. Berrino∗; L. Botta; A. Trama; R. Lillini; A. Bernasconi; S. Bonfarnuzzo; C. Vener; F. Didonè; P. Lasalvia; L. Buratti; G. Tagliabue (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan); L. Dal Maso; F. Toffolutti (Centro di Riferimento Oncologico, IRCCS, Aviano for the Friuli Venezia Giulia CR); R. Capocaccia∗ (Epidemiologia & Prevenzione Board); R. De Angelis∗; E. Demuru; F. Cerza; F. Di Mari; C. Di Benedetto; S. Rossi∗; M. Santaquilani; S. Venanzi; M. Tallon (Istituto Superiore di Sanità, Rome); L. Boni (Genova CR); S. Iacovacci (Latina CR); C. Genova; D. Malacarne (Liguria, Mesotheliomas CR); A. G. Russo; F. Gervasi (Province of Milan and Lodi CR); G. Spagnoli (Modena CR); L. Cavalieri d’Oro (Monza and Brianza CR); M. Fusco; R. Abbate (Naples 3 South CR); P. Pinna (Nuoro CR); W. Mazzucco (Palermo CR); M. Michiara (Parma CR); G. Chiaranda (Piacenza CR); G. Cascone; M. C. Giurdanella (Ragusa CR); L. Mangone (Reggio Emilia CR); F. Falcini (Romagna CR); R. Cavallo (Salerno CR); D. Piras (Sassari CR); A. Madeddu; F. Bella (Siracusa CR); A. C. Fanetti (Sondrio CR); S. Minerba (Taranto CR); G. Candela; T. Scuderi (Trapani CR); W. Mantovani; M. A. Gentilini (Trento CR); F. Stracci (Umbria CR); M. Zorzi; S. Guzzinati (Veneto CR); N. Ferrarini (Viterbo CR); Latvia: E. Liepina (National CR); Lithuania: G. Smailyte (National CR); Malta: M. Azzopardi; N. Calleja (National CR); Norway: T. B. Johannesen∗ (National CR); Poland: J. Didkowska; U. Wojciechowska (National CR); M. Bielska-Lasota∗; Portugal: A. Pais (Central Portugal CR); M. J. Bento; A. M. Ferreira (Northern Portugal CR); A. Lourenço; A. Mayer (Southern Portugal CR); Slovakia: C. Safaei Diba (National CR); Slovenia: V. Zadnik; T. Zagar (National CR); Spain: P. Ruiz Armengol (Balearic Islands, Mallorca CR); A. Lopez de Munain; M. De-La-Cruz (Basque Country CR); M. Garrido (Canary Islands CR); A. Vizcaino (Castellon CR); R. Marcos-Gragera; A. Sanvisens (Girona CR, CIBERESP); M. J. Sanchez; D. Redondo-Sanchez (Granada CR, EASP, ibs.GRANADA, CIBERESP); M. D. Chirlaque Lopez; A. Sanchez-Gil (Murcia CR, CIBERESP); M. Guevara∗; E. Ardanaz (Navarra CR, CIBERESP); J. Galceran; M. Carulla (Tarragona CR); Switzerland: Y. Bergeron (Fribourg CR); A. Flahault; R. Schaffar (Geneva CR); R. Von Moos (Graubünden and Glarus CR); S. Mohsen Mousavi; M. Blum (Eastern Switzerland CR); A. Bordoni (Ticino CR); The Netherlands: O. Visser∗ (National CR); UK-England: S. Stevens; J. Broggio (National CR); UK-Northern Ireland: D. Bennett (National CR); A. Gavin∗; UK-Scotland: D. Morrison (National CR); UK-Wales: D. W. Huws∗; S. Smits (Welsh Cancer Intelligence and Surveillance—WCISU).
Funding
None declared.
Disclosure
The authors have declared no conflicts of interest.
Footnotes
EUROCARE Steering Committee Member.
Contributor Information
A. Trama, Email: Annalisa.trama@istitutotumori.mi.it.
EUROCARE-6 Working Group:
K. Innos, V. Jooste, A. Monnereau, A. Katalinic, G. Gatta, M. Sant, P. Baili, F. Berrino, R. Capocaccia, R. De Angelis, S. Rossi, T.B. Johannesen, M. Bielska-Lasota, M. Guevara, O. Visser, A. Gavin, and D.W. Huws
Supplementary data
References
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