Distinct clinical features and epidemiological trends of very early and middle-aged early onset colorectal cancer based on SEER 17 and GBD 2021 data over the past 15 years

Abstract

Background

The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. There may be differences in pathological characteristics and epidemiological trends between different subgroups of EOCRC, which warrants further investigation.

Materials

We utilized the Surveillance, Epidemiology, and End Results (SEER) 17 database and the Global Burden of Disease (GBD) 2021 data to analyze clinical, prognostic, and epidemiological differences by dividing EOCRC into Very Early Onset Colorectal Cancer (VEOCRC, ages 15–29) and Mid-Aged Early Onset Colorectal Cancer (MAEOCRC, ages 30–49) over the past 15 years. Statistical analyses included Kaplan-Meier survival analysis, joinpoint regression, average annual percentage change (AAPC) analysis, decomposition analysis.

Results

The VEOCRC group had a significantly higher proportion of mucinous adenocarcinoma/signet ring cell carcinoma (MA/SRCC) (18.1% vs. 8.7%) and more advanced histologic grades III and IV (32.2% vs. 18.9%) compared to MAEOCRC. There were no significant pathological differences between MAEOCRC and Late-onset CRC (LOCRC). VEOCRC had a worse prognosis than MAEOCRC, especially at stage III. From 2006 to 2021, the age-standardized incidence rate (ASIR) for VEOCRC grew faster than for MAEOCRC globally (AAPC: 0.78 vs. 0.63), notably in high-middle Socio-demographic Index (SDI) countries (AAPC: 2.01 vs. 1.44). Excluding carcinoid tumors, the incidence of VEOCRC in high SDI countries has remained stable over the past 15 years, whereas in high-middle SDI countries, it surpassed high SDI countries as early as 2013, reaching the highest globally. Decomposition analysis revealed that in high-middle SDI countries, epidemiological changes contributed more to the increase in VEOCRC compared to MAEOCRC.

Conclusions

VEOCRC and MAEOCRC differ significantly in clinical characteristics, prognosis, and epidemiology, with VEOCRC showing worse pathology and prognosis. In the past 15 years, the global incidence of VEOCRC has risen faster than MAEOCRC, warranting particular attention from policymakers, especially in high-middle SDI countries.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12885-025-15263-w.

Background

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide, posing a significant public health challenge [1]. Traditionally, CRC was predominantly associated with individuals aged 50 and above. However, recent epidemiological studies have indicated a significant rise in early-onset colorectal cancer (EOCRC), which is now being diagnosed in individuals under 50 years of age [2, 3]. This rise is particularly alarming because EOCRC often presents at more advanced stages and with distinct pathological features compared to Late-onset CRC (LOCRC), leading to poorer prognoses and increased healthcare burdens globally [4].

Despite the growing body of research on EOCRC, most studies describing the clinical and pathological characteristics of EOCRC are primarily retrospective and single-center series with small sample sizes [5]. The largest of these includes just over 1,000 early-onset colorectal cancer patients [5], often treating individuals under 50 as a homogeneous group without adequately distinguishing between different age subgroups. In the first edition of Adolescent and Young Adult (AYA) Oncology, which encompasses patients diagnosed with colorectal cancer between the ages of 15 and 29 [6], there is a growing interest in understanding the unique characteristics and outcomes of this age group. For instance, a study from the Netherlands reported that patients aged 20–29 had a higher incidence of signet ring cell carcinoma and significantly poorer tumor differentiation compared to those aged 30–49, indicating a more aggressive disease phenotype in younger patients [7]. The ARCAD Clinical Trials Program also concluded that prognosis worsens with decreasing age among individuals under 50, suggesting that Very Early Onset CRC (VEOCRC) patients may have distinct biological backgrounds necessitating separate consideration [8]. Therefore, larger datasets are needed to further validate the clinical characteristics and prognostic differences between age groups in EOCRC.

In terms of incidence, studies from Europe and the United States have found that the incidence of EOCRC in the 20–29 age group was significantly higher than in the 30–49 age group between 1990 and 2016 [9, 10]. However, contrary to these findings, a study from Italy reported an overall decline in EOCRC incidence, with the most significant decrease observed in the 20–29 age group [11]. It is important to note that the aforementioned studies used ICD-O-3 (International Classification of Diseases for Oncology, Third Edition) classification criteria for colorectal cancer, which includes carcinoid tumors [12]. These tumors tend to show a faster increase in incidence compared to more common types like adenocarcinoma in EOCRC [13]. However, carcinoid tumors generally have a significantly lower mortality rate than adenocarcinoma [14]. Therefore, to better understand the recent incidence rates of EOCRC across different age groups, it is more recommended to use ICD-10 (International Classification of Diseases, Tenth Revision) classification. Unlike ICD-O-3, ICD-10 explicitly excludes carcinoid tumors from the colorectal cancer category, providing a clearer picture of the trends in more common types of colorectal cancer [15].

In the Global Burden of Disease (GBD) 2021 database, new location-years of data from population-based cancer registries and vital registration systems were added, and it used ICD-10 classification to exclude the interference of carcinoid tumors. Therefore, we used the GBD 2021 database to explore the global disease burden of early-onset colorectal cancer, particularly focusing on VEOCRC and the differences within various age groups of EOCRC.

By using 30 years of age as a threshold, we categorized EOCRC patients into VEOCRC and Mid-Aged Early Onset CRC (MAEOCRC). Utilizing the most recent data from the Surveillance, Epidemiology, and End Results Program (SEER 17) database and the GBD 2021, we aimed to delve deeper into the clinical characteristics and epidemiological trends of these patients over the past 15 years. Our goal is to enhance our understanding and improve the clinical management of this patient population.

Methods

Data source and research design

In this study, we utilized the SEER database [SEER 17 Regs Research Data, Nov 2022 Sub (2000–2020)] to analyze data from 2004 to 2019. To bolster the robustness of our analysis and elucidate differences in clinical features and prognostic factors, we excluded cases with unknown TNM stage, histological grading, treatment type, unclear primary site, and primary tumors that did not meet international standards. Additionally, we censored some pathological types (mainly carcinoid tumors), including only the most clinically common adenocarcinomas (AD) (8140, 8144, 8201, 8210, 8211, 8213, 8220, 8221, 8255, 8260, 8261, 8262, 8263, 8310, 8323) and signet ring cell carcinoma (SRCC) or mucinous adenocarcinoma (MA) (8480, 8481, 8490) for the analyses. The inclusion criteria for processing the SEER database are detailed in Additional file 1.

The GBD 2021 provides comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations from 1990 to 2021 [16]. For the GBD study, we chose to use data from 2006 to 2021. This period aligns better with our research interests, allowing us to focus on the most recent trends and developments over the past 15 years. Using these specific time frames for SEER and GBD data allowed us to leverage the best available data from each source to enhance the robustness and relevance of our findings.

Definition of CRC

We classified all cases coded as C18-C21 as CRC based on ICD-10 standards. VEOCRC was defined as CRC in patients aged 15–29, aligning with AYA oncology guidelines (typically 15–29 or 15–39 years) and epidemiological data showing a marked 2.7-fold increase in cancer incidence from age 15 onward [6]. This cutoff also aligns with the 5-year age groupings used in our databases, making 15 a practical starting point. The upper limit of 30 was chosen based on regional data indicating significant shifts in CRC incidence around this age [9]. Consequently, we defined VEOCRC as ages 15–29, MAEOCRC as 30–49, and LOCRC as 50 and older.

Statistical analysis

We compared between-group differences in VEOCRC, MAEOCRC, and LOCRC in the SEER database using the chi-square test, with Bonferroni correction applied for multiple comparisons. The Kaplan-Meier method and log-rank test were utilized for survival analysis regarding Cancer-Specific Survival (CSS) and Overall Survival (OS). Subgroup analyses were performed using the “jstable” R package.

In the GBD database, a 95% uncertainty interval (UI) was calculated for each variable [16, 17]. The database furnished crucial information on incidence, mortality, and Disability-Adjusted Life Years (DALYs), facilitating a comprehensive assessment of disease burden. We derived age-standardized rates for incidence, mortality, and DALYs using the WHO world standard population from 2000 to 2025. Average annual percentage changes (AAPC) were calculated to assess trends, with weights based on the length of each period [18]. The 95% confidence interval (CI) was obtained from the linear regression model. If the AAPC value and 95% CI were above zero, the age-standardized rate (ASR) showed an upward trend; otherwise, it showed a downward trend. We also calculated the mortality-to-incidence ratio (MIR), defined as the age-standardized mortality rate (ASMR) divided by the age-standardized incidence rate (ASIR). Joinpoint regression analysis was used to assess trends in EOCRC disease burden with software from the U.S. National Cancer Institute to evaluate the changes in incidence and mortality trends across different Socio-Demographic Index (SDI) regions. In our analysis of relative income-related inequalities between countries, we utilized the slope index of inequality (SII) to assess the disparities in health outcomes. The SII specifically measures inequalities in ASMR across different income groups, offering a quantitative evaluation of the health disparity gradient. Additionally, decomposition analyses were used to visualize the role of three factors (i.e., aging, demographic, and epidemiologic) that drive changes in incidence and mortality between 2006 and 2021 [19].

All tests were two-sided and p-values less than 0.05 were considered significant. All statistical analyses and graphs were performed using R version 4.2.1.

Results

Clinical, and pathological characteristics of VEOCRC, MAEOCRC, and LOCRC patients

Table 1 highlights the variations in clinical characteristics among the VEOCRC, MAEOCRC, and LOCRC groups. Gender distribution showed slight differences, with higher proportions of males in the VEOCRC and MAEOCRC groups (53.7% vs. 52.9% vs. 52.1%). The VEOCRC group had a significantly higher proportion of MA/SRCC (18.1% vs. 8.7% vs. 8.7%, P < 0.001), while the difference in the proportion of MA/SRCC between MAEOCRC and LOCRC was not statistically significant (P = 0.641). Additionally, the VEOCRC group exhibited more advanced histologic grades III and IV (32.2% vs. 18.9% vs. 18.2%, P < 0.001). Both VEOCRC and MAEOCRC presented at more advanced AJCC stages compared to LOCRC. The incidence of N1-2 colorectal cancer was higher in the younger age groups (63% vs. 54.6% vs. 40.0%, P < 0.001), and the M1 stage also showed a higher proportion in younger ages (24.1% vs. 20.8% vs. 13.4%, P < 0.001). Tumor diameter was larger in the VEOCRC and MAEOCRC groups, with a higher proportion of tumors larger than 3 cm (72.0% vs. 67.4% vs. 61.3%, P < 0.001). Regarding treatment modalities, the VEOCRC and MAEOCRC groups were more likely to receive chemotherapy and radiotherapy (Chemotherapy: 72.9% vs. 65.7% vs. 36.5%, P < 0.001; Radiation: 22.5% vs. 25.1% vs. 13.2%, P < 0.001). In terms of tumor location, VEOCRC and MAEOCRC were more inclined to be located in the left colon and rectum.

Table 1.

Characteristics of very early onset colorectal cancer, Mid-Aged early onset colorectal cancer and late onset colorectal cancer patients

	VEOCRC	MAEOCRC	LOCRC	P-val
	(N = 1662)	(N = 36659)	(N = 325302)
Sex
Female	771 (46.4%)	17,273 (47.1%)	155,850 (47.9%)	0.0242
Male	891 (53.6%)	19,386 (52.9%)	169,452 (52.1%)
Race
White	1257 (75.6%)	27,670 (75.5%)	263,430 (81.0%)	< 0.001
Black	201 (12.1%)	4785 (13.1%)	33,451 (10.3%)
Others	204 (12.3%)	4204 (11.5%)	28,421 (8.7%)
Histologic_type
AD	1362 (81.9%)	33,459 (91.3%)	297,146 (91.3%)	< 0.001
MA/SRCC	300 (18.1%)	3200 (8.7%)	28,156 (8.7%)
Grade
I	110 (6.6%)	2849 (7.8%)	30,235 (9.3%)	< 0.001
II	1018 (61.3%)	26,860 (73.3%)	235,890 (72.5%)
III	468 (28.2%)	6100 (16.6%)	52,250 (16.1%)
IV	66 (4.0%)	850 (2.3%)	6927 (2.1%)
T
T1	193 (11.6%)	4771 (13.0%)	55,597 (17.1%)	< 0.001
T2	125 (7.5%)	4313 (11.8%)	49,775 (15.3%)
T3	932 (56.1%)	20,872 (56.9%)	172,296 (53.0%)
T4	412 (24.8%)	6703 (18.3%)	47,634 (14.6%)
N
N0	615 (37.0%)	16,653 (45.4%)	195,123 (60.0%)	< 0.001
N1	507 (30.5%)	11,545 (31.5%)	82,135 (25.2%)
N2	540 (32.5%)	8461 (23.1%)	48,044 (14.8%)
M
M0	1262 (75.9%)	29,034 (79.2%)	281,803 (86.6%)	< 0.001
M1	400 (24.1%)	7625 (20.8%)	43,499 (13.4%)
Stage
I	206 (12.4%)	6431 (17.5%)	86,805 (26.7%)	< 0.001
II	343 (20.6%)	8682 (23.7%)	97,364 (29.9%)
III	713 (42.9%)	13,921 (38.0%)	97,634 (30.0%)
IV	400 (24.1%)	7625 (20.8%)	43,499 (13.4%)
Size
<= 3 cm	274 (16.5%)	7574 (20.7%)	89,990 (27.7%)	< 0.001
>3 cm	1196 (72.0%)	24,697 (67.4%)	199,495 (61.3%)
Unknown	192 (11.6%)	4388 (12.0%)	35,817 (11.0%)
Site
Left colon	733 (44.1%)	16,437 (44.8%)	114,996 (35.4%)	< 0.001
Rectum	423 (25.5%)	10,234 (27.9%)	60,323 (18.5%)
Right colon	506 (30.4%)	9988 (27.2%)	149,983 (46.1%)
Surgeryperformed
No	102 (6.1%)	2053 (5.6%)	17,339 (5.3%)	0.137
Yes	1560 (93.9%)	34,606 (94.4%)	307,963 (94.7%)
Radiation
No	1288 (77.5%)	27,464 (74.9%)	282,339 (86.8%)	< 0.001
Yes	374 (22.5%)	9195 (25.1%)	42,963 (13.2%)
Chemotherapy
No/Unknown	450 (27.1%)	12,587 (34.3%)	206,702 (63.5%)	< 0.001
Yes	1212 (72.9%)	24,072 (65.7%)	118,600 (36.5%)

VEOCRC Very Early Onset Colorectal Cancer, MAEOCRC Mid-Aged Early Onset Colorectal Cancer, LOCRC Late Onset Colorectal Cancer, AD Adenocarcinoma, MA/SRCC Mucinous Adenocarcinoma/Signet Ring Cell Carcinoma

Prognostic analysis of VEOCRC, MAEOCRC, and LOCRC patients

We analyzed the prognosis of CRC patients across different age groups. When OS was the outcome, LOCRC had a worse prognosis than VEOCRC (P < 0.001); MAEOCRC had the best prognosis (P < 0.001). When CSS was the outcome, VEOCRC had a worse prognosis than LOCRC (P = 0.019); the best prognosis still possessed by MAEOCRC (P < 0.001).

We further explored the prognostic performance of CSS and OS in each group at the same clinical stage. The results indicated that LOCRC had a significantly worse prognosis than the other two groups at all clinical stages (P < 0.001). Specifically, there was no significant difference in CSS between VEOCRC and MAEOCRC at stages I, II, and IV. However, VEOCRC had a worse prognosis than MAEOCRC at stage III (P < 0.001) (Fig. 1). A similar pattern was observed when OS was used as the endpoint (Additional file 2).

Fig. 1.

Prognostic Analysis of Kaplan-Meier (KM) between Different CRC Age Groups. (A) Overall Survival (OS) analysis between different CRC age groups (B) Cancer-Specific Survival (CSS) analysis between different CRC age groups (C) CSS analysis at stage I (D) CSS analysis at stage II (E) CSS analysis at stage III (F) CSS analysis at stage IV

Subgroup analysis comparing VEOCRC and MAEOCRC for CSS revealed that VEOCRC had a worse prognosis than MAEOCRC in most subgroups, with no significant interaction observed between the groups. Moreover, when we categorized all patients into three treatment statuses: Surgery only, Surgery + Chemotherapy ± Radiation, and Chemotherapy ± Radiation, there was no significant difference in CSS between the two groups in the Surgery only category. However, in the other two categories, MAEOCRC had a worse prognosis compared to VEOCRC (Additional file 3). This trend was consistent AD and MA/SRCC subtypes (Additional file 4).

Global incidence, mortality, and dalys of VEOCRC and MAEOCRC from 2006 to 2021

Table 2 present the case numbers along with the ASIR and AAPC of VEOCRC and MAEOCRC globally from 2006 to 2021. The case numbers for mortality and DALYs, as well as ASMR and age-standardized DALYs rate (ASDR) data, are provided in the (Additional file 5. 6). The ASIR for VEOCRC was 0.73 (95% UI: 0.69 to 0.76) per 100,000 in 2006 and 0.79 (95% UI: 0.72 to 0.87) per 100,000 in 2021, with an AAPC of 0.78 (95% CI: 0.51–1.04). For MAEOCRC, the ASIR was 8.42 (95% UI: 8.11 to 8.76) per 100,000 in 2006 and 9.15 (95% UI: 8.31 to 10.07) per 100,000 in 2021, with an AAPC of 0.63 (95% CI: 0.50–0.77). Despite the higher total increase in MAEOCRC cases, the ASIR for VEOCRC grew faster (AAPC: 0.78 vs. 0.63). Additionally, it was found that in 2019–2021, two years after the emergence of COVID-19, the incidence rates of both VEOCRC and MAEOCRC declined to varying degrees. The ASIR for VEOCRC decreased by 2.47%, from 0.81 (95% UI: 0.74–0.89) to 0.79 (95% UI: 0.72–0.87), while the ASIR for MAEOCRC decreased by 1.19%, from 9.26 (95% UI: 8.51–10.09) to 9.15 (95% UI: 8.38–10.00.38.00), with VEOCRC showing a greater percentage decline. Subgroups based on gender show that the increase in incidence from 2006 to 2021 for both VEOCRC and MAEOCRC is concentrated in males, while no significant increase in incidence is observed in females (Fig. 2A-B).

Table 2.

Incidence of very early onset colorectal cancer and Mid-Aged early onset colorectal cancer from 2006 to 2021

Location	Case(n), 2006	ASIR per 100 000 population (95% UI), 2006	Case(n), 2021	ASIR per 100 000 population (95% UI), 2021	AAPC_95CI(2006–2021)	P-Value
VEOCRC
Global	12129.85 (11416.20–12665.06.20.06)	0.73 (0.69–0.76)	14388.27 (13049.20–15767.16.20.16)	0.79 (0.72–0.87)	0.78 (0.51–1.04)	< 0.001
Sex
Female	5430.06 (5055.41–5761.68.41.68)	0.65 (0.61–0.69)	5949.28 (5302.19–6737.99.19.99)	0.66 (0.59–0.75)	0.19 (−0.03–0.41.03.41)	0.086
Male	6699.79 (6032.15–7136.00)	0.80 (0.72–0.85)	8438.99 (7358.32–9521.03.32.03)	0.91 (0.80–1.03)	0.85 (0.58–1.12)	< 0.001
SDI
High SDI	2524.60 (2451.26–2600.02.26.02)	1.19 (1.16–1.23)	2465.78 (2351.29–2592.85.29.85)	1.17 (1.11–1.23)	−0.21 (−0.54-0.13.54.13)	0.222
High-middle SDI	3207.49 (2942.03–3474.98.03.98)	1.08 (0.99–1.17)	3539.42 (3050.27–4108.39.27.39)	1.43 (1.23–1.66)	2.01 (1.78–2.25)	< 0.001
Middle SDI	4159.77 (3841.46–4441.99.46.99)	0.75 (0.69–0.80)	5357.99 (4710.25–6051.59.25.59)	0.96 (0.85–1.09)	1.84 (1.56–2.13)	< 0.001
Low-middle SDI	1658.61 (1484.55–1836.50.55.50)	0.40 (0.36–0.44)	2117.75 (1815.78–2615.44.78.44)	0.41 (0.35–0.51)	0.12 (−0.00–0.25.00.25)	0.058
Low SDI	568.14 (480.82–663.19.82.19)	0.29 (0.25–0.34)	895.82 (740.28–1058.06.28.06)	0.30 (0.25–0.36)	0.26 (0.07–0.44)	0.007
Region
Andean Latin America	87.66 (74.07–104.07.07.07)	0.64 (0.54–0.76)	119.92 (93.23–153.46.23.46)	0.68 (0.53–0.87)	0.46 (−0.06–0.98.06.98)	0.077
Australasia	71.35 (60.67–83.47)	1.43 (1.22–1.67)	89.48 (72.30–108.84.30.84)	1.37 (1.11–1.66)	−0.69 (−1.17–0.22)	0.007
Caribbean	102.05 (88.10–116.99.10.99)	0.98 (0.85–1.12)	119.68 (98.18–143.19.18.19)	1.05 (0.86–1.26)	0.84 (0.49–1.20)	< 0.001
Central Asia	138.49 (126.82–152.02.82.02)	0.65 (0.59–0.71)	138.04 (120.43–156.67.43.67)	0.60 (0.52–0.68)	−0.49 (−1.10-0.12.10.12)	0.115
Central Europe	239.83 (226.09–253.79.09.79)	0.85 (0.80–0.90)	162.94 (146.21–177.81.21.81)	0.82 (0.74–0.90)	−0.36 (−1.48-0.77.48.77)	0.526
Central Latin America	446.91 (423.68–471.42.68.42)	0.77 (0.73–0.82)	653.83 (576.89–732.18.89.18)	1.02 (0.90–1.14)	1.74 (0.59–2.90)	0.003
Central Sub-Saharan Africa	48.91 (35.63–67.24)	0.22 (0.16–0.30)	93.96 (64.34–133.76.34.76)	0.26 (0.18–0.37)	1.36 (1.21–1.52)	< 0.001
East Asia	3961.64 (3510.35–4418.12.35.12)	1.21 (1.08–1.35)	5236.34 (4278.86–6343.28.86.28)	2.01 (1.64–2.44)	3.51 (3.20–3.82)	< 0.001
Eastern Europe	446.28 (429.34–465.30)	0.86 (0.82–0.89)	245.76 (223.33–272.59.33.59)	0.73 (0.66–0.81)	−1.53 (−2.01–1.04)	< 0.001
Eastern Sub-Saharan Africa	292.11 (246.01–338.71.01.71)	0.38 (0.32–0.43)	478.90 (383.13–624.89.13.89)	0.41 (0.33–0.54)	0.70 (0.59–0.81)	< 0.001
High-income Asia Pacific	390.16 (362.09–422.94.09.94)	1.07 (0.99–1.16)	342.81 (304.45–387.90)	1.13 (1.01–1.28)	0.16 (−0.12–0.44.12.44)	0.235
High-income North America	991.82 (960.71–1028.09.71.09)	1.43 (1.39–1.48)	967.44 (914.18–1019.64.18.64)	1.28 (1.21–1.34)	−0.90 (−1.60–0.19)	0.013
North Africa and Middle East	885.38 (774.73–999.67.73.67)	0.64 (0.56–0.72)	1210.30 (1026.88–1414.75.88.75)	0.79 (0.67–0.92)	1.50 (1.33–1.66)	< 0.001
Oceania	10.08 (7.11–13.19)	0.39 (0.28–0.51)	15.46 (10.99–20.70)	0.42 (0.30–0.56)	0.75 (0.49–1.00.49.00)	< 0.001
South Asia	1092.54 (971.36–1211.73.36.73)	0.27 (0.24–0.30)	1288.66 (1065.50–1782.51.50.51)	0.25 (0.21–0.35)	−0.55 (−1.06–0.03)	0.038
Southeast Asia	1327.59 (1081.59–1528.16.59.16)	0.84 (0.68–0.96)	1571.60 (1302.69–1841.97.69.97)	0.91 (0.75–1.06)	0.52 (0.37–0.68)	< 0.001
Southern Latin America	147.52 (124.17–174.47.17.47)	1.02 (0.86–1.20)	175.41 (141.55–211.63.55.63)	1.08 (0.87–1.31)	0.05 (−0.76–0.87.76.87)	0.901
Southern Sub-Saharan Africa	113.10 (94.38–130.00)	0.57 (0.48–0.66)	99.44 (82.74–128.60)	0.47 (0.39–0.61)	−1.35 (−1.66–1.04)	< 0.001
Tropical Latin America	357.53 (335.85–381.09.85.09)	0.66 (0.62–0.71)	448.57 (418.57–480.40)	0.83 (0.77–0.89)	1.45 (1.08–1.81)	< 0.001
Western Europe	857.30 (811.88–911.58.88.58)	1.06 (1.00–1.12.00.12)	708.87 (652.51–768.51.51.51)	0.91 (0.84–0.99)	−1.29 (−2.05–0.52)	0.001
Western Sub-Saharan Africa	121.60 (95.73–147.12.73.12)	0.15 (0.12–0.18)	220.86 (156.96–299.43.96.43)	0.17 (0.12–0.23)	1.04 (0.75–1.34)	< 0.001
MAEOCRC
Global	147808.07 (142389.42–153926.96.42.96)	8.42 (8.11–8.76)	197502.09 (179356.39–217329.35.39.35)	9.15 (8.31–10.07)	0.63 (0.50–0.77)	< 0.001
Sex
Female	63943.41 (60923.61–67017.63.61.63)	7.36 (7.01–7.71)	79275.18 (72319.06–87349.45.06.45)	7.40 (6.75–8.15)	0.06 (−0.03–0.14.03.14)	0.176
Male	83864.66 (79000.97–89242.58.97.58)	9.45 (8.91–10.06)	118226.91 (102538.25–135623.76.25.76)	10.88 (9.44–12.48)	1.03 (0.92–1.15)	< 0.001
SDI
High SDI	47286.01 (45808.91–48805.97.91.97)	15.05 (14.58–15.53)	48519.04 (46537.10–50576.40.10.40)	15.09 (14.47–15.73)	0.01 (−0.23–0.24.23.24)	0.95
High-middle SDI	43597.97 (40989.39–46721.42.39.42)	11.38 (10.70–12.20)	58594.28 (50018.01–69145.77.01.77)	14.22 (12.14–16.77)	1.44 (1.28–1.60)	< 0.001
Middle SDI	41017.18 (38221.87–44197.27.87.27)	6.94 (6.47–7.48)	64798.59 (55998.15–73964.39.15.39)	8.96 (7.74–10.23)	1.73 (1.54–1.91)	< 0.001
Low-middle SDI	12174.01 (11029.10–13428.17.10.17)	3.56 (3.23–3.92)	19284.27 (16821.10–22236.10.10.10)	4.01 (3.49–4.61)	0.92 (0.82–1.02)	< 0.001
Low SDI	3583.98 (3144.16–4090.81.16.81)	2.71 (2.38–3.09)	6140.98 (5269.33–7171.90.33.90)	2.87 (2.46–3.35)	0.35 (0.24–0.46)	< 0.001
Region
Andean Latin America	520.13 (439.37–613.25.37.25)	4.35 (3.67–5.13)	911.32 (697.10–1176.45.10.45)	5.18 (3.96–6.68)	1.21 (0.69–1.72)	< 0.001
Australasia	1209.82 (1046.18–1394.37.18.37)	15.66 (13.55–18.03)	1570.78 (1292.72–1884.28.72.28)	18.03 (14.84–21.63)	0.92 (−0.23–2.09.23.09)	0.119
Caribbean	1147.19 (1014.77–1299.57.77.57)	9.95 (8.80–11.28.80.28)	1420.45 (1172.06–1686.93.06.93)	11.06 (9.13–13.14)	0.68 (0.05–1.32)	0.035
Central Asia	1040.07 (968.53–1122.91.53.91)	4.88 (4.54–5.27)	1211.72 (1058.01–1368.16.01.16)	4.64 (4.05–5.24)	0.09 (−0.18–0.36.18.36)	0.509
Central Europe	4518.61 (4277.31–4773.99.31.99)	12.44 (11.77–13.15)	4254.88 (3848.90–4684.74.90.74)	11.36 (10.27–12.51)	−0.40 (−0.65–0.16)	0.003
Central Latin America	2837.88 (2674.65–3029.20.65.20)	5.31 (5.01–5.68)	5474.01 (4843.26–6182.39.26.39)	7.81 (6.91–8.82)	2.92 (2.73–3.11)	< 0.001
Central Sub-Saharan Africa	362.31 (270.26–477.12.26.12)	2.30 (1.71–3.02)	706.63 (496.64–1019.85.64.85)	2.77 (1.94–3.99)	1.31 (1.20–1.42)	< 0.001
East Asia	49535.64 (44971.25–55334.06.25.06)	11.08 (10.05–12.41)	76453.00 (61046.57–94056.17.57.17)	16.71 (13.37–20.55)	2.86 (2.48–3.25)	< 0.001
Eastern Europe	7181.25 (6893.86–7481.90.86.90)	10.11 (9.70–10.53.70.53)	6911.89 (6292.02–7602.67.02.67)	10.48 (9.54–11.53)	0.22 (−0.43–0.87.43.87)	0.506
Eastern Sub-Saharan Africa	1605.40 (1414.02–1827.03.02.03)	3.47 (3.05–3.94)	2843.86 (2367.87–3592.67.87.67)	3.60 (3.00–4.54.00.54)	0.24 (0.14–0.34)	< 0.001
High-income Asia Pacific	8589.11 (7979.07–9299.64.07.64)	15.59 (14.48–16.88)	8539.64 (7695.23–9479.41.23.41)	14.75 (13.27–16.37)	−0.33 (−0.47–0.18)	< 0.001
High-income North America	18172.47 (17556.14–18823.74.14.74)	17.22 (16.64–17.84)	18424.13 (17557.44–19313.63.44.63)	18.63 (17.75–19.52)	0.44 (−0.05–0.94.05.94)	0.077
North Africa and Middle East	5935.66 (5251.40–6725.99.40.99)	5.43 (4.81–6.15)	11895.86 (10197.78–13869.77.78.77)	6.66 (5.70–7.76)	1.48 (1.33–1.64)	< 0.001
Oceania	60.29 (47.36–73.99)	2.84 (2.24–3.48)	91.32 (71.15–116.30)	2.80 (2.19–3.57)	0.04 (−0.10–0.18.10.18)	0.565
South Asia	8850.66 (8023.31–9705.61.31.61)	2.60 (2.36–2.85)	14222.73 (12340.94–16949.55.94.55)	2.93 (2.55–3.49)	0.82 (0.57–1.08)	< 0.001
Southeast Asia	11129.39 (9515.29–12636.64.29.64)	6.94 (5.94–7.88)	16397.72 (13437.10–19210.72.10.72)	8.03 (6.58–9.41)	1.11 (1.03–1.19)	< 0.001
Southern Latin America	1420.62 (1243.42–1628.98.42.98)	9.08 (7.94–10.41)	1920.97 (1627.39–2247.95.39.95)	9.91 (8.39–11.60)	0.39 (−0.16–0.94.16.94)	0.162
Southern Sub-Saharan Africa	889.72 (767.80–999.56.80.56)	5.78 (5.00–6.49.00.49)	1219.29 (1035.49–1467.52.49.52)	5.76 (4.90–6.91)	−0.11 (−0.40-0.18.40.18)	0.444
Tropical Latin America	3378.19 (3170.01–3622.59.01.59)	6.37 (5.98–6.84)	5488.96 (5106.49–5940.19.49.19)	8.00 (7.44–8.66)	1.24 (1.08–1.40)	< 0.001
Western Europe	18487.72 (17323.89–19728.95.89.95)	14.03 (13.16–14.97)	15872.06 (14711.33–17115.82.33.82)	12.71 (11.78–13.71)	−0.79 (−1.19–0.39)	< 0.001
Western Sub-Saharan Africa	935.93 (746.09–1106.53.09.53)	1.71 (1.36–2.02)	1670.87 (1241.62–2148.61.62.61)	1.90 (1.41–2.44)	0.78 (0.59–0.97)	< 0.001

VEOCRC Very Early-Onset Colorectal Cancer, MAEOCRC Middle-Aged Early-Onset Colorectal Cancer, ASIR Age-standardized incidence rate, SDI Socio-demographic index, AAPC Average annual percentage change

Fig. 2.

Rates, case numbers and DALYs of Early-Onset Colorectal Cancer (EOCRC) by Sex Globally (2006–2021) (A) Age-standardized incidence rate (ASIR) and case numbers in Very Early-Onset Colorectal Cancer (VEOCRC) (B) ASIR and case numbers in Middle-Aged Early-Onset Colorectal Cancer (MAEOCRC) (C) Age-standardized death rate (ASMR) and case numbers in VEOCRC (D) ASMR and case numbers in MAEOCRC (E) DALYs and age-standardized DALYs rate (ASDR) in VEOCRC (F) DALYs and ASDR in MAEOCRC

From 2006 to 2021, the ASMR for both VEOCRC and MAEOCRC showed a slight decline. The decrease was more pronounced in VEOCRC (AAPC = −0.56; 95% CI: −0.69 to −0.44) compared to MAEOCRC (AAPC = −0.44; 95% CI: −0.57 to −0.32) (Fig. 2C-D). A similar trend was observed in the ASDR (Fig. 2E-F). In addition, we calculated the MIR, which was 0.49 for VEOCRC and 0.44 for MAEOCRC in 2006, and 0.41 for VEOCRC compared to 0.37 for MAEOCRC in 2021. This indicates that the MIR was consistently higher for VEOCRC compared to MAEOCRC over the years.

Incidence and mortality of VEOCRC and MAEOCRC across SDI and regions from 2006 to 2021

We explored the differences in the incidence rates of VEOCRC and MAEOCRC across regions with different SDI levels. Among the high SDI countries, no significant incidence change was found in the overall AAPC for either VEOCRC or MAEOCRC from 2006 to 2021 (VEOCRC: −0.21 [95% CI: −0.54 to 0.13], P = 0.222; MAEOCRC: 0.01 [95% CI: −0.23 to 0.24], P = 0.95). However, Joinpoint analysis indicated that VEOCRC showed a mild elevation during 2006–2017 (APC = 0.37, P = 0.004), but significantly decreased during 2017–2021 (APC = −1.78, P = 0.01), with a similar trend observed in MAEOCRC. Meanwhile, there was a significant increase in the incidence of both VEOCRC and MAEOCRC in high-middle SDI and middle SDI countries. Notably, in high-middle SDI countries, the AAPC value of VEOCRC for 2006–2021 was 2.01 (95% CI: 1.78 to 2.25), which was significantly higher than that of MAEOCRC at 1.44 (95% CI: 1.28 to 1.60). In fact, VEOCRC in high-middle SDI countries surpassed high SDI countries as the area with the highest incidence in 2013, while high SDI countries remained the highest for MAEOCRC. Conversely, the incidence of MAEOCRC increased at a faster rate in low and low-mid SDI countries, especially in low-middle SDI countries (MAEOCRC AAPC: 0.92 [95% CI: 0.82 to 1.02], P < 0.001; VEOCRC AAPC: 0.12 [95% CI: −0.00 to 0.25], P = 0.058) (Fig. 3; Table 2).

Fig. 3.

Age-standardized incidence rates (ASIR) over time by SDI Location. (A) ASIR in Very Early-Onset Colorectal Cancer (B) ASIR in Middle-Aged Early-Onset Colorectal Cancer (*: P < 0.05)

In terms of the 21 GBD regions, it was found that East Asia had the highest 2021 incidence of VEOCRC with an ASR of 2.01 (95% UI: 1.64 to 2.44) and also had the fastest growth rate of VEOCRC from 2006 to 2021, with an AAPC of 3.51 (95% CI: 3.20 to 3.82) (Table 2). Specifically, in China, the VEOCRC burden increased dramatically over the 15-year period, with an ASR of 2.03 (95% UI: 1.65 to 2.48) and an AAPC of 3.67 (95% CI: 3.35 to 4.00) in 2021. In contrast, changes in VEOCRC incidence in developed East Asian countries such as Japan and South Korea remained relatively stable (Japan AAPC: −0.05 [95% CI: −0.80 to 0.70], P = 0.888; Republic of Korea AAPC: −0.23 [95% CI: −1.00 to 0.54], P = 0.527). Regarding MAEOCRC, High-income North America had the highest ASR in 2021 at 18.63 (95% UI: 17.75 to 19.52), but there was no significant change over the 2006–2021 period (AAPC: −0.44 [95% CI: −0.05 to 0.94], P = 0.077). The fastest growing region for MAEOCRC was Central Latin America (AAPC: 2.92 [95% CI: 2.73 to 3.11]). In East Asia, the incidence of MAEOCRC also grew at a fast rate (AAPC: 2.86 [95% CI: 2.48 to 3.25]), although the rate was lower than that of VEOCRC. The ASIRs for VEOCRC and MAEOCRC in 2021 for 204 countries, along with the AAPC for the period from 2006 to 2021, are presented in Fig. 4.

Fig. 4.

The age-standardized incidence rate (ASIR) of Very Early-Onset Colorectal Cancer (VEOCRC) and Middle-Aged Early-Onset Colorectal Cancer (MAEOCRC) in 204 countries and territories in 2021, with the average annual percentage changes (AAPC) for the period from 2006 to 2021 (A) The ASIR of VEOCRC (B) The ASIR of MAEOCRC (C) The AAPC of VEOCRC (D) The AAPC of MAEOCRC

Additionally, we observed that the incidence of VEOCRC and MAEOCRC are not increasing at the same rate in many countries. For instance, in the United Arab Emirates from 2006 to 2021, VEOCRC had an AAPC of 4.19 (95% CI: 0.88 to 7.61), whereas MAEOCRC had an AAPC of −3.25 (95% CI: −3.66 to −2.84). In Singapore, from 2006 to 2021, VEOCRC had an AAPC of 3.67 (95% CI: 2.03 to 5.33), while MAEOCRC had an AAPC of 0.19 (95% CI: −0.96 to 1.35, P = 0.745). However, some countries in southeastern Europe, such as Albania, Estonia, and Greece, have seen a marked decline in VEOCRC incidence and a relative stabilization of MAEOCRC incidence (Additional file 7).

In terms of mortality, the ASMR in the high-middle SDI areas are the highest, and the high SDI with high incidence rates are already lower than those in the high-middle and middle SDI areas in both VEOCRC and MAEOCRC in 2021 (Additional file 5). The ASMRs for VEOCRC and MAEOCRC in 2021 for 204 countries, along with the AAPC for the period from 2006 to 2021, are presented in Additional file 8. Across all 204 countries analyzed, we conducted health inequality analyses and observed a gradual decrease in ASMR differences across SDIs over the 15-year period. This trend was particularly notable in VEOCRC, where the difference in ASMR between the highest SDI region and the lowest SDI region in 2021 was only 0.0952 (95% CI: 0.0606 to 0.130) (Additional file 9).

Decomposition analysis

We performed a decomposition analysis of factors influencing VEOCRC and MAEOCRC globally across different SDI levels. In populations with high-middle and middle SDI levels, epidemiological changes had a greater impact on VEOCRC compared to MAEOCRC. Specifically, the increases in VEOCRC due to epidemiological changes accounted for 291.9% and 97.6% of the overall increase, respectively. For MAEOCRC, the corresponding increases were 74.3% and 55.3%. Conversely, low birth rates negatively affected the growth of VEOCRC in high-middle SDI populations, with the contribution of low birth rates to the overall increase being − 256.27% (Fig. 5).

Fig. 5.

Decomposition of Incidence between 2006 and 2021, by Global, SDI (A) Decomposition of Very Early-Onset Colorectal Cancer (B) Decomposition of Middle-Aged Early-Onset Colorectal Cancer

Discussion

Many previous studies have reported an increased proportion of SRCC or MA in EOCRC compared to LOCRC [7, 20–22]. Our study found that these poor histologic types were concentrated in VEOCRC. In contrast, the histologic types were very similar between MAEOCRC and LOCRC, with no clear statistical differences. Similarly, some small retrospective studies have reported a significant increase in the proportion of SRCC and MA in individuals under 30 years of age [7]. This finding aligns with a Chinese study, which reported the proportions of SRCC/MA in stage III CRC patients under 30, 30–49, and over 50 years of age as 10.3%, 3.6%, and 2.1%, respectively, with no statistically significant differences between the latter two groups [22]. Therefore, it is crucial to recognize the distinct histologic distribution between VEOCRC and MAEOCRC.

In terms of prognosis, there are some differences in the available studies, primarily due to possible variations in the inclusion criteria. Additionally, the influence of certain types such as familial or multiple polyposis and carcinoid tumors, which are more prevalent in young people and have a better prognosis, were not excluded, potentially affecting the results. In our study, only the three most common pathological types—AD, SRCC, and MA—were included. Familial or multiple polyposis cases documented in the SEER database were excluded to minimize their potential influence on the results. Patients with VEOCRC demonstrated markedly poorer OS and CSS compared to those with MAEOCRC. Notably, the CSS for VEOCRC was even worse than that observed in the LOCRC group. This survival deficit is likely attributable to the more aggressive clinicopathological features associated with VEOCRC, including a higher prevalence of unfavorable histologic types, more advanced grades, and higher clinical staging at diagnosis. This clinical finding is further corroborated by epidemiological data from GBD 2021, where the MIR for VEOCRC has consistently been higher than that of MAEOCRC. Several studies have also reported similar results [23, 24]. However, specific to CSS for each stage, we found that LOCRC was inferior to VEOCRC because VEOCRC patients received more aggressive treatments, particularly at stage IV (VEOCRC vs. LOCRC: 22.1% vs. 11.7% for radiotherapy and 89.3% vs. 63.2% for chemotherapy). In contrast, MAEOCRC had better CSS than VEOCRC only at stage III, while no significant prognostic differences were found for the other stages. Liying Zhao et al. analyzed the prognosis of 995 CRC patients in China, using 35 years of age as the cut-off point, and found that younger patients had a worse prognosis than older patients only at stage III [25], similar to our results. Other studies have also found similar outcomes, showing a worse prognosis for younger patients with stage III CRC [22]. In summary, these results indicate that LOCRC patients have worse OS due to their older age and inability to undergo aggressive treatments. Aggressive treatments may improve the CSS for VEOCRC patients; however, despite this, VEOCRC patients still have the worst CSS due to poorer histological differentiation and staging. On the other hand, MAEOCRC patients benefit from better overall health and more favorable pathological staging, leading to the best CSS outcomes.

VEOCRC may exhibit unique molecular mechanisms that contribute to distinct pathologic characteristics and prognostic differences [26]. For example, research indicates that CMS1 colorectal cancer, a subtype associated with immune response, is linked to a lower survival rate compared to other subtypes [27, 28]. In a study involving 36,000 CRC patients, the CMS1 subtype was significantly more prevalent in patients under 40 years old compared to those over 40 [29], potentially contributing to the poor prognosis observed in VEOCRC patients [30]. Moreover, the higher incidence of mucinous adenocarcinoma and signet ring cell carcinoma in VEOCRC may be attributed to specific biological or genetic factors. Notably, studies have identified a higher frequency of SMAD4 mutations in VEOCRC cases, particularly in mucinous adenocarcinomas [26]. These mutations are associated with a more aggressive tumor phenotype, contributing to the poorer prognosis typical of these pathologic subtypes [31, 32]. As for why stage III VEOCRC prognosis is significantly worse than MAEOCRC, we believe it may be related to the increased proportion of MA/SRCC in stage III and IV VEOCRC cases, while the generally poor prognosis in stage IV makes it difficult to differentiate. Further research into the biological and genetic underpinnings could elucidate why these specific pathologic types are more prevalent and impactful in younger patients.

We next explored possible epidemiologic differences between VEOCRC and MAEOCRC. We found that the incidence of VEOCRC grew slightly faster than that of MAEOCRC over the 15-year period. However, both incidence rates declined in the two years following the 2019–2021 COVID-19 outbreak, with the decline being significantly greater for VEOCRC compared to MAEOCRC (2.47% vs. 1.19%). Removing the decline from COVID-19, the growth rate of VEOCRC may be more pronounced. This larger decline for VEOCRC can be attributed to numerous nonurgent medical procedures, including routine colonoscopies and other colorectal cancer screenings, being delayed or canceled during the pandemic [33]. The COVID-19 pandemic led to a significant economic downturn, with widespread unemployment and disruptions in health insurance coverage, which may have contributed to the observed decline in CRC incidence rates [34]. Moreover, studies from Italy, Japan, and the United States have reported an increase in the proportion of late-stage colorectal cancer cases following the onset of COVID-19 [35–37]. To address this situation, remedial measures such as immediate catch-up screenings are crucial to minimize the pandemic’s impact [38]. A modeling study published in 2021 for Australia, Canada, and the Netherlands indicated that up to a 12-month disruption in screening could increase CRC incidence by 0.6–1.8%. However, implementing immediate catch-up screening could reduce this impact to less than 0.1% by 2050 [39]. Sex-stratified analysis showed a significant increase in ASIR in males for both VEOCRC and MAEOCRC, while females did not exhibit a significant change. This disparity may be partly attributed to the higher susceptibility of men to risk factors such as smoking and drinking [40].

We further analyzed the incidence and mortality of VEOCRC and MAEOCRC across different SDI levels. Among high SDI countries, we did not find a significant difference in the growth rate of VEOCRC and MAEOCRC incidences, which is somewhat inconsistent with some current studies. Several studies from the United States and Europe indicate that CRC incidence is rising most rapidly among individuals aged 15–29 years [9, 10], possibly due to different inclusion criteria. Notably, the GBD 2021 explicitly excludes carcinoid tumors. When assessing VEOCRC incidence in the United States using the SEER 17 for the years 2006–2020, we found that the AAPC for 2006–2020 was 5.85% when carcinoid tumors were included, but only 0.65% when they were not included, and the difference was not statistically significant (P >0.05) (Additional file 10). In contrast, high-middle and middle SDI countries adopting Western diets and lifestyles have experienced rapid increases in both VEOCRC and MAEOCRC incidences [41], with VEOCRC increasing more substantially. China, in particular, shows among the highest ASIR, with growth rates surpassing those of MAEOCRC. Regarding mortality, the ASMR for VEOCRC in high SDI countries has significantly declined, likely due to early screening and disease resection initiatives in countries such as the United States [42]. However, China presents a contrasting scenario with an increasing ASMR for VEOCRC. Decomposition analyses revealed that the changes in VEOCRC incidence due to epidemiological factors were significantly higher compared to those in MAEOCRC in high-middle and middle SDI countries. However, changes in population proportions, such as lower birth rates resulting from China’s family planning policies, have made the actual growth in VEOCRC numbers less apparent. Finally, we found that the incidence growth rates of VEOCRC and MAEOCRC from 2006 to 2021 varied greatly between countries. In one-third of the countries, the 15-year AAPC difference between the two was greater than 1%, which is likely due to differences in the pathogenesis and pathology. This is underscored by evidence of a significant hereditary component in the youngest patients; for instance, a landmark report from the MD Anderson Cancer Center found that as many as one-third of colorectal cancer patients diagnosed under the age of 35 have a hereditary predisposition [43]. This fundamental difference in etiology likely contributes to the distinct epidemiological trends and pathological features we have reported.

The common approach is to consider individuals under 50 as a single group when analyzing early-onset colorectal cancer. However, our results indicate that those younger than 30 have distinct staging, prognosis, and epidemiological characteristics compared to those aged 30–49. This suggests a need for focused attention on diagnosis and treatment for patients under 30 to explore reasons for their poorer prognosis. The significant rise in ASIR for VEOCRC in high-middle and middle SDI countries—likely influenced by birth cohort effects from recent economic growth—underscores this importance. Notably, in 2006, the ASIR in high-middle SDI countries was lower than in high SDI countries; by 2021, it had surpassed high SDI levels, reaching 1.2 times the ASIR observed in high SDI regions. Experiences from high SDI countries demonstrate that early screening, particularly through colonoscopy, is critical in reducing colorectal cancer incidence [44]. A 2023 prospective study analyzing dietary quality in over 29,000 women aged 25–42 found a positive correlation between Western dietary patterns and CRC diagnosis [45]. Additionally, systematic reviews have identified a strong association between obesity in early adulthood (≤ 30 years) and increased CRC risk [46]. Therefore, policymakers in high-middle and middle SDI nations should promote earlier and more frequent screenings for younger individuals with gastrointestinal symptoms and encourage healthy lifestyles to counteract factors driving the younger trend in CRC [47]. Moreover, in high SDI countries, the inclusion or exclusion of carcinoid tumors significantly affects epidemiological trends in CRC. Our SEER analysis confirms that when carcinoid tumors are included, the incidence of VEOCRC appears alarmingly high but is less dramatic when they are excluded. This highlights the importance of precise pathological classification in epidemiological studies and suggests that policymakers should consider the unique characteristics of carcinoid tumors when designing CRC-related health policies.

In treating VEOCRC, surgery remains a primary and effective approach, yielding a prognosis similar to MAEOCRC, especially in patients with very early-stage disease. This similarity holds across different pathological types, such as AD and MA/SRCC, where surgery alone results in nearly identical 5-year and 10-year survival rates between VEOCRC and MAEOCRC (Additional file 4). Early detection and timely, high-quality radical surgery are fundamental for improving prognosis, highlighting the importance of targeted early screening to prevent disease progression. However, once chemotherapy or radiotherapy is required, the prognosis for VEOCRC becomes significantly worse compared to MAEOCRC—for example, in Stage III MA/SRCC patients, the median survival time for VEOCRC is only 67 months, while it reaches 124 months for MAEOCRC (Additional file 4). Therefore, while less invasive surgeries like local excision may achieve good outcomes for early-stage (Stage I) patients, more comprehensive curative resections are recommended for mid-stage (Stages II and III) patients to improve outcomes (Additional file 11). Moreover, for Stages III patients, comprehensive preoperative and postoperative treatments may benefit their long-term survival (Additional file 12). Targeted early screening is therefore critical for VEOCRC patients to prevent disease advancement to later stages. Early detection and timely surgery not only improve survival rates but also reduce socio-economic burdens. Due to limitations in the SEER database in capturing precise surgical timing, future studies with more detailed timing data are needed to better define the optimal timing for surgery in VEOCRC patients.

There are several limitations to this study. Firstly, the SEER data has retrospective bias and lacks specific treatment options. Secondly, the GBD data was obtained through estimation and mathematical modeling, which may affect the accuracy and reliability of the burden estimation. Potential biases could arise from data collection variations across different countries, impacting the GBD estimates. Additionally, the data does not clearly specify tumor sites or pathology types, and due to incomplete information on risk factors for very young bowel cancer, we did not account for specific risk factor differences in VEOCRC and MAEOCRC.

Conclusions

Our study revealed that worse pathological types, higher histological grades, and poorer prognoses in EOCRC are primarily concentrated in VEOCRC compared to MAEOCRC. Over the past 15 years, the incidence of VEOCRC has risen more rapidly than that of MAEOCRC, particularly in regions with high-middle SDI. However, despite the ASIR observed in 2021, after excluding carcinoid tumors, the VEOCRC incidence in high SDI countries has remained relatively stable over the past 15 years. These findings highlight the distinct clinical and epidemiological characteristics of VEOCRC and underscore the need for targeted prevention and management strategies in this population.

Abbreviations

AD

Adenocarcinoma

AAPC

Average annual percentage change

AJCC

American Joint Committee on Cancer

APC

Annual percent change

ASDR

Age-standardized DALYs rate

ASIR

Age-standardized incidence rate

ASMR

Age-standardized mortality rate

ASR

Age-standardized rate

AYA

Adolescent and Young Adult

CI

Confidence interval

CSS

Cancer-specific survival

CRC

Colorectal cancer

DALYs

Disability-adjusted life years

EOCRC

Early-onset colorectal cancer

GBD

Global Burden of Disease

ICD

International Classification of Diseases

LOCRC

Late-onset colorectal cancer

MA

Mucinous adenocarcinoma

MAEOCRC

Middle-Aged Early Onset Colorectal Cancer

MIR

Mortality-to-incidence ratio

OS

Overall survival

SDI

Socio-Demographic Index

SEER

Surveillance, Epidemiology, and End Results

SII

Slope index of inequality

SRCC

Signet ring cell carcinoma

UI

Uncertainty interval

VEOCRC

Very Early Onset Colorectal Cancer

WHO

World Health Organization

Authors’ contributions

Conceptualization: HP, BX; Data Curation: XJ, BB; Formal Analysis: SX, YP, FW, XG, LY, YC; Writing – Original Draft: SX, YP, KD, FW, XG, LY; Writing – Review & Editing: All authors; Equal Contribution: XJ, BB, YP (co-first authors); Approval of Final Manuscript: All authors.

Funding

None.

Data availability

All data generated or analysed during this study are included in this published article [and its supplementary information files].

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.