In this population-based study, data from 17 SEER registries in the United States were collected to analyze cancer cases in individuals under the age of 25 from 2000 to 2020. To our knowledge, this is the first report on the incidence and long-term overall survival patterns for CAYA cancer survivors in the past 20 years in the USA. The overall age-standardized incidence rate (ASIR) of CAYA cancer was 19.26 per 100,000 in 2000 and 21.47 per 100,000 in 2020. The trends in the incidence rate of CAYA cancer increased, with the incidence rate in males higher than that in females. Additionally, the overall 5-year relative survival rate of CAYA cancer increased from 80.40% (95% CI, 78.84%-81.87%) in 2000 to 87.80% (95% CI, 86.65%-88.86%) in 2015, with the 5-year relative survival rate for females under 25 years reaching 89.86%, higher than that for males (85.58%).
Previous studies on cancer incidence have often focused on early-onset cancers, typically under the age of 50[6]. Among individuals under 50 years old, breast, thyroid, and colon and/or rectum cancers are more common than other sites[6]. However, breast and thyroid cancers are not common in individuals younger than 25, whereas leukemia, lymphoma, brain and other nervous system cancers, male genital system cancers, and digestive system cancers are more prevalent, accounting for more than 50% of all sites in CAYA individuals. This suggests that there are different characteristics of tumor onset in CAYA individuals. In the following Table 6, we summarized the incidence and survival rates of common cancers among individuals of different ages and regions. In recent years, the common sites of CAYA tumors have changed compared to before, with the blood system, nervous system, and male genital system becoming more common. Moreover, there are differences in common cancers between different age groups and regions. For example, in individuals aged 15 to 39 years, breast cancer is common, but not in those younger than 25 years old (Table 7).
Table 7
Comparative of common cancer and survival rates in CAYA cancer patients. (Supplement data)
Author | Data source | Publication year | Investigation period | Region | Age range | Common cancer | Survival rate |
Beatriz de Camargo et al.[8] | PBCR | 2010 | 1991–2004 | Brazil | 0 to 19 years | Male: Leukemia, Lymphoma, CNS tumors; | —— |
Meerim Park et al.[9] | KCCR | 2016 | 1993–2016 | Korea | 15 to 39 years | Thyroid carcinoma, Carcinoma of Gastrointestinal Tract, Carcinoma of Breast, Carcinoma of Genitourinary Tract; | Thyroid carcinoma (100.1%), Carcinoma of Gastrointestinal Tract (69.7%), Carcinoma of Breast (100.5%), Carcinoma of Genitourinary Tract (92.8%);b |
Annalisa Trama et al.[10] | EUROCARE-5 | 2016 | 2000–2007 | Europe | 15 to 39 years | Male: Germ cell tumours, trophoblastic tumours, and neoplasms of gonads, Malignant melanomas, Hodgkin lymphomas; Female: Breast carcinomas, Female genital tract carcinomas, Malignant melanomas; | Male: Germ cell tumours, trophoblastic tumours, and neoplasms of gonads (94·9%), Malignant melanomas(84.0%), Hodgkin lymphomas (91.8%);b Female: Breast carcinomas (83.5%), Female genital tract carcinomas (81.6%), Malignant melanomas (91.9%);b |
Alyssa R. Scott et al.[11] | the SEER Database 18 registry research data | 2020 | 1973–2015 | the US | 15 to 39 years | Male: Germ Cell and Trophoblastic Neoplasms of Gonads, Melanoma, Non-Hodgkin lymphoma; Female: Breast, Thyroid carcinoma, Carcinoma of the Cervix and Uterus; | —— |
Chengqi Xiao et al. | the SEER Database 17 registry research data | —— | 2000–2020 | the US | 0 to 25 years | Leukemia, Lymphoma, Brain and other nervous system, Male genital system, Digestive system; | Leukemia (72.53%), Lymphoma (93.38%), Brain and other nervous system (79.07%), Male genital system (94.89%), Digestive system (81.02%);c |
The SEER Database: Surveillance, Epidemiology, and End Results Database; EUROCARE: European Cancer Registry Based Study on Survival and Care of Cancer Patients; Korea National Cancer |
Incidence database in the Korea Central Cancer Registry; CNS, central nervous system; PBCR: The Brazilian Population-Based Cancer Registry; |
a, 5-relative survival rate, 2012–2016; b, relative survival rate, population weighted; c, 5-relative survival rate,2016.
Table 6. Comparative of common cancer and survival rate among younger people.
In our study, we observed that leukemia, lymphoma, brain and other nervous system cancers, endocrine system cancers, and male genital system cancers were the top five cancer types, collectively accounting for more than 60% of all CAYA cancer cases. Additionally, there was a notable increase in digestive system cancers, while the incidence of skin cancers excluding basal and squamous cell carcinoma, as well as female genital system cancers, declined. Various factors are associated with cancer in CAYA individuals, including intrauterine radiation exposure[12], transplacental exposure to environmental carcinogens[13] smoking, exposure to environmental tobacco smoke[14], and inherited genetic factors[15]. The use of colonoscopy has been beneficial for screening colorectal cancer[16]. The advancement of auxiliary examination techniques such as ultrasound, CT, and MRI, along with the application of puncture biopsy, has led to a rapid increase in the incidence of thyroid cancer, although concerns about overdiagnosis exist[17, 18]. Public health efforts targeting melanoma have resulted in a decline in its incidence among CAYA individuals[19, 20]. The significant decrease in the incidence of cervical cancer can be attributed to the widespread use of the HPV vaccine[18, 21]. However, some cancers, like osteosarcoma, have not seen significant treatment breakthroughs[22], leading to minimal changes in survival rates.
The overall 5-year relative survival rate of CAYA cancer increased from 80.40% (95% CI, 78.84%-81.87%) in 2000 to 87.80% (95% CI, 86.65%-88.86%) in 2015. With advancements in treatment technology, such as genome-based and immunologic-based treatments, the cure rate of cancer in CAYA individuals has improved[23, 24].
The higher survival rates have led to an increase in CAYA cancer survivors, who face dual challenges transitioning from precancerous states to survivors and from childhood or adolescence to adulthood[25]. Apart from cancer affecting their growth[26], two-thirds of CAYA survivors are at a particular risk of long-term sequelae from the cancer itself or the therapies used[27]. Compared to healthy individuals, adolescent and young adult (AYA) cancer survivors are at a higher risk of poor health-related quality of life due to a higher burden of total chronic health conditions (CHCs)[28].
Lager epigenetic age accelerations were measured among children and adolescent cancer survivors associated with early-onset obesity, morbidity burden in general, and late mortality[29]. Children and adolescent cancer survivors, especially those from low- and middle-income backgrounds, are more likely to experience physical late effects, including hypothyroidism, metabolic syndrome, gonadal dysfunction, cardiac dysfunction, and even secondary primary cancer[30, 31]. Psychological problems are also more severe in young cancer patients[32]. Additionally, CAYA cancer survivors are at risk of delayed cancer diagnosis[33]. Collectively, these individuals require more psychological and social support[34].
Common cancer treatments such as radiotherapy and chemotherapy can impair reproductive health and fertility[35–40]. Compared to healthy individuals, cancer survivors are 80% more likely to experience diminished fertility after cancer treatments[41]. Female cancer survivors are particularly vulnerable to fertility damage due to the destruction of ovarian function[42]. Premature ovarian insufficiency (POI), which impacts fertility and estrogen production, can occur in about 30% of cases within 2 years after cancer diagnosis[43]. POI can manifest as acute ovarian failure (AOF) in the years following cancer treatment, leading to either the cessation of menstruation or the failure to achieve natural menarche. POI can also result in premature menopause after cancer treatment, leading not only to infertility but also to premature aging of the body. The risk of AOF and POI depends on factors such as age, cyclophosphamide equivalent dose (CED), and the quantity of radiation (RT). For example, with a high CED, the risk of AOF is greater than 5% for individuals aged 1–20 with a dose to the least affected ovary (LAO) of less than 2 Gy, and the risk of POI by age 20 approaches 100%[44]. Children born to female cancer survivors are at an increased risk of being born preterm and with low birth weight[45, 46]. Similarly, some male cancer survivors experience reduced sperm count and azoospermia due to treatments such as high cumulative radiation[37, 47]. For instance, when the mean testicular dose exceeds 1 Gy, the rate of oligospermia increases to over 90% at 12 months[48]. These cancer survivors often experience mental depression due to the damage to their reproductive function, which can be particularly severe in females compared to males[49]. Therefore, the reproductive health of young cancer survivors is a critical aspect of their overall well-being that cannot be ignored.
Oncofertility focuses on addressing the intersection of oncology and reproductive medicine to preserve or restore the reproductive function of cancer survivors[50]. Fertility preservation (FP) involves specific medical interventions to protect the fertility of individuals at risk of infertility due to their disease or its treatment. This can include cryopreservation of oocytes, embryos, ovarian tissue, sperm, and testicular tissue[51]. The gold standards of FP in female cancer patients are oocyte and embryo vitrification. With the advancements in assisted reproductive technology (ART), an increasing number of female cancer survivors have been able to have offspring[52]. Other FP techniques for females include ovarian tissue cryopreservation[53, 54], in vitro maturation (IVM) [55] and stem cell regeneration [56]. Stem cells currently under study for FP include embryonic stem cells (ESCs)[57], human pluripotent stem cells (hPSCs)[58] and mesenchymal stem cells (MSCs).Further, MSCs contained human amniotic epithelial cells (hAECs)[59], umbilical cord mesenchymal stem cells (UC-MSCs)[60], human placenta-derived mesenchymal stem cell (hPMSC)[61]. Anti-Müllerian hormone (AMH) decreased or undetectable after treatment in cancer survivors can be regard as an indicator of ovarian function[62]. For male cancer patients, the FP gold standard is sperm cryopreservation, with cryopreservation of testicular tissue and in vitro spermatogenesis as complementary options[52]. Spermatogonial stem cells (SSCs), which have the ability to self-renew and differentiate, are considered an ideal tissue for cryopreservation[63]. Additionally, raising awareness among young cancer survivors about the potential long-term reproductive effects of cancer treatment is a priority in current care.[64]. Therefore, more efforts should be focused on FP for young cancer survivors to help preserve their fertility and improve their quality of life after cancer treatment.
To our knowledge, this is the first report on the cancer incidence and survival rates among individuals younger than 25 years old in the USA over the past 20 years. However, this study has some limitations. Firstly, the majority of participants were White, whereas some reports suggest that the incidence and prognosis of certain cancers are related to race[65–67]. Secondly, the study did not consider the impact of the coronavirus disease 2019 (COVID-19) pandemic, as there was a lag in statistical data. Some studies have indicated that COVID-19 may affect the incidence and survival rates of cancer[68, 69]. Finally, our study was based on the SEER database, and as cancer incidence can vary by region, further research is needed to explore the incidence and survival of cancer in individuals under 25 years old globally.