Published online Nov 28, 2026. doi: 10.3748/wjg.120795
Revised: March 26, 2026
Accepted: April 10, 2026
Published online: November 28, 2026
Processing time: 206 Days and 12.3 Hours
The prognosis of early-onset gastric cancer (EOGC) remains debated. Comparing EOGC directly with older patients can bias survival outcomes due to differences in life expectancy and age-related comorbidities. To isolate the specific oncological behavior of EOGC, comparisons with mid-aged patients are necessary. We hypo
To compare clinicopathological characteristics and survival outcomes between EOGC and M-GC using an evidence-based age cutoff and inverse probability of treatment weighting (IPTW).
We analyzed a single-center surgical registry of patients who underwent gastrec
A total of 637 patients were included; 105 (16.5%) were classified as having EOGC. Diffuse-type histology was more frequent in EOGC; patients with EOGC had fewer comorbidities and a lower Charlson comorbidity index. In the entire cohort, EOGC demonstrated superior 5-year RFS compared with M-GC [80.74% vs 72.18%; hazard ratio (HR), 0.57; 95% confidence interval (CI): 0.360-0.890; P = 0.014], whereas 5-year OS was comparable between the groups (78.38% vs 75.33%; HR, 0.69; 95%CI: 0.461-1.033; P = 0.072). After IPTW adjustment, 5-year RFS and OS were significantly higher in the EOGC group. Stage-stratified analyses showed consistently favorable RFS in EOGC, with a significant difference observed in stage III disease.
EOGC shows favorable survival despite aggressive histology. High treatment tolerance justifies optimistic coun
Core Tip: This study compares early-onset gastric cancer (EOGC) and mid-aged gastric cancer (M-GC) using an evidence-based age cutoff of 50 years and inverse probability of treatment weighting to minimize age-related confounders. Despite a higher pre
- Citation: Jeong SA, Lee JB, Kim JH. Clinicopathological characteristics and survival outcomes of early-onset vs mid-aged gastric cancer using an evidence-based age cutoff. World J Gastroenterol 2026; 32(44): 120795
- URL: https://www.wjgnet.com/1007-9327/full/v32/i44/120795.htm
- DOI: https://dx.doi.org/10.3748/wjg.120795
An increasing incidence of cancer among younger populations has emerged as a global public health concern. The global cancer burden in young adults is predicted to increase by approximately 12% from 2022 to 2025[1]. Large population-based studies have demonstrated that several gastrointestinal malignancies, including gastric cancer, are being diagnosed at progressively younger ages[2]. Although gastric cancer has traditionally been regarded as a disease of older adults, early-onset gastric cancer (EOGC) now represents a distinct and expanding clinical subgroup[3]. As the epidemiologic profile of gastric cancer continues to evolve, a clearer understanding of the clinicopathological characteristics and prog
EOGC has been reported to exhibit clinicopathological features that differ from those of gastric cancer diagnosed at a typical age. EOGC is more frequently associated with diffuse-type histology, signet ring cell carcinoma, and advanced disease at diagnosis[7-9]. In addition, younger patients with gastric cancer generally have fewer underlying comorbidities and may tolerate aggressive treatment strategies more effectively[1,2]. However, whether these characteristics translate into differences in survival outcomes remains unclear.
Previous studies evaluating the prognosis of EOGC have reported heterogeneous results of survival outcomes and disease characteristics when compared with gastric cancer diagnosed at a typical age[7-9]. Inconsistencies in the specific age used as cutoff, from 30 years to 50 years, have led to conflicting results and substantial heterogeneity in the existing literature regarding the prognosis of EOGC. Consequently, the clinical and prognostic implications of EOGC remain incompletely understood. Large-scale, multicenter cohort studies have proposed an age cutoff of 50 years to define EOGC, providing a more consistent framework for evaluating its clinicopathological characteristics and survival out
Based on this evolving framework, we conducted a retrospective analysis to evaluate the clinicopathological characteristics and survival outcomes of EOGC, defined using an evidence-based age cutoff of 50 years. Patients with mid-aged gastric cancer (M-GC) were used as a comparison group to minimize confounding from advanced age and competing non-cancer mortality. This study aimed to clarify disease characteristics and stage-stratified prognostic implications of EOGC in comparison with M-GC.
The institutional registry of gastric neoplasms at Gangneung Asan Hospital has prospectively maintained surgical and clinicopathological data since 2013. The registry data, derived from Electronic Medical Records, were prospectively collected after obtaining informed consent. Follow-up information regarding survival and recurrence is updated at each outpatient visit. Postoperative follow-up was performed every 3-6 months in accordance with the Korean Gastric Cancer Association guidelines[11]. Recurrence was confirmed via biopsy or, when biopsy was unfeasible, by clinical and radiolo
From this registry, we identified patients who underwent gastrectomy for gastric adenocarcinoma between January 2013 and March 2020. To ensure adequate 5-year survival assessment and minimize the impact of mortality from non-cancer causes, only patients aged ≤ 75 years at the time of surgery were included. The life expectancy of the general Korean population was 82.55 years in 2013, which gradually increased to 84.55 years in 2022[12]. Patients who underwent gastrectomy for neoplasms other than gastric adenocarcinoma were excluded.
The following variables were collected: Age, sex, body mass index (BMI), medical history, comorbidities, Charlson comorbidity index (CCI), operative time, type of gastrectomy, number of retrieved and metastatic lymph nodes (LN), tumor size, Lauren classification, lymphovascular invasion, perineural invasion, tumor multiplicity, extent of LN dissection and omentectomy, pathological stage according to the 8th edition of the American Joint Committee on Cancer TNM classification[13], use of adjuvant chemotherapy, postoperative complications, in-hospital mortality, and recurrence and survival status.
To minimize missing data and ensure data integrity, two independent clinicians reviewed the electronic medical records to verify any missing or inconsistent values in the original registry. Through this manual cross-verification process, missingness was kept to a minimum, and all key clinicopathological variables were successfully captured for the final analysis.
The extent of resection was categorized into total gastrectomy, subtotal gastrectomy, and palliative resection, the latter defined as R1 or R2 resection with non-curative intent. Postoperative complications were assessed during hospitalization or within 30 days after surgery and were graded according to the Clavien-Dindo classification system[14].
Two groups were defined for comparison: The EOGC group (age ≤ 50 years) and the M-GC group (age 51-75 years). Baseline characteristics, pathological features, and surgical outcomes were compared between the two groups.
Survival analyses were performed according to pathological TNM stage. Five-year recurrence-free survival (RFS) was evaluated in patients with stage I, II, and III disease who underwent curative resection. Five-year overall survival (OS) was assessed across all stages (I-IV). For stage IV analysis, all patients who underwent palliative surgery, including R1 or R2 resections, were included. Stage IV patients were excluded from the RFS analysis due to baseline metastatic disease but were included in the OS analysis to evaluate the OS profile of the entire cohort.
Categorical variables are presented as n (%), and continuous variables are reported as mean ± SD. Fisher’s exact test was used for comparisons of categorical variables, as appropriate. Survival outcomes, including 5-year OS and RFS, were estimated using the Kaplan-Meier method, and comparisons were evaluated using Cox proportional hazards models.
To reduce potential confounding, survival analyses were additionally conducted using inverse probability of treatment weighting (IPTW)[15]. Propensity scores for each patient were calculated based on the following covariates: Sex, comorbidities, Lauren classification, lymphovascular invasion, perineural invasion, postoperative complications, and receipt of adjuvant chemotherapy, which were selected based on their established prognostic significance in gastric cancer and potential. To evaluate the performance and robustness of the IPTW-adjusted models, we assessed the balance of covariates using standardized mean differences (SMD) and compared the distribution of weights. Additionally, the Hosmer-Lemeshow test was performed to ensure the goodness-of-fit of the models. All balance assessment methods indicated that the baseline characteristics were well balanced between the two groups after weighting. A two-sided P value < 0.05 was considered statistically significant. All statistical analyses were performed using R version 4.4.2 (R Foundation for Statistical Computing, Vienna, Austria).
This study was conducted in accordance with the Declaration of Helsinki. The institutional gastric neoplasm registry at Gangneung Asan Hospital contains retrospectively collected data prior to 2023 and has been maintained prospectively thereafter. The establishment of the prospective registry and its data collection procedures were approved by the Institutional Review Board (No. GNAH 2024-02-001). For the prospective component, all eligible patients provided written informed consent and were informed of their right to withdraw consent at any time. The present study, which analyzed both retrospective and prospective registry data, received separate Institutional Review Board approval (No. GNAH 2025-05-018).
A total of 702 patients aged ≤ 75 years underwent gastrectomy for gastric neoplasms during the study period. After excluding 63 patients with non-adenocarcinoma pathology, 639 patients with gastric adenocarcinoma were identified. All eligible patients were included in the analysis of clinicopathological characteristics. For survival analyses, patients who underwent R1 resection (n = 4) were excluded (Figure 1). Among the overall study population, 105 patients (16.5%) and 532 patients (83.5%) were classified as the EOGC and M-GC groups, respectively.
Baseline characteristics are summarized in Table 1. The proportion of female patients was higher in the EOGC group than in the M-GC group (33.33% vs 25.56%). The EOGC group had significantly fewer comorbidities (31.4% vs 57.9%, P < 0.001) and a lower CCI (2.66 ± 1.31 vs 4.50 ± 1.43, P < 0.001), whereas BMI and prior malignancy history were comparable between the two groups. The distribution of pathological TNM stage was also similar (P = 0.290), with no significant differences in the proportions of stage I-IV disease.
| Variables | EOGC (n = 105) | M-GC (n = 532) | P value |
| Age (year) | 44.51 ± 4.25 | 63.95 ± 7.16 | < 0.001 |
| Sex | 0.101 | ||
| Male | 70 (66.67) | 396 (74.44) | |
| Female | 35 (33.33) | 136 (25.56) | |
| BMI (kg/m2) | 24.22 ± 4.03 | 23.84 ± 3.69 | 0.357 |
| Underlying disease | 33 (31.43) | 308 (57.89) | < 0.001 |
| Previous history of other malignancies | 4 (3.81) | 42 (7.89) | 0.139 |
| CCI score | 2.66 ± 1.31 | 4.50 ± 1.43 | < 0.001 |
| Extent of resection | 0.369 | ||
| Subtotal gastrectomy | 72 (68.57) | 399 (75.00) | |
| Total gastrectomy | 26 (24.76) | 108 (20.30) | |
| Palliative resection | 7 (6.67) | 25 (4.70) | |
| pTNM stage | 0.290 | ||
| I | 49 (46.67) | 298 (56.02) | |
| II | 24 (22.86) | 104 (19.55) | |
| III | 24 (22.86) | 105 (19.74) | |
| IV | 8 (7.62) | 25 (4.70) |
Pathological findings among patients undergoing radical resection are summarized in Table 2. Lauren classification differed markedly between the groups, with EOGC showing a substantially higher proportion of diffuse-type tumors compared to M-GC (52.6% vs 22.3%, P < 0.001). EOGC demonstrated a lower rate of lymphovascular invasion (24.7% vs 35.2%, P = 0.046) and more frequent perineural invasion (34.0% vs 24.3%, P = 0.044). Other pathological variables-including tumor size, depth of invasion, nodal status, number of retrieved or metastatic LNs, and tumor multiplicity-did not differ significantly.
| Variables | EOGC (n = 97) | M-GC (n = 503) | P value |
| pT stage | 0.521 | ||
| T1a | 26 (26.80) | 126 (25.05) | |
| T1b | 23 (23.71) | 156 (31.01) | |
| T2 | 9 (9.28) | 54 (10.74) | |
| T3 | 25 (25.77) | 99 (19.68) | |
| T4 | 14 (14.43) | 68 (13.52) | |
| pN stage | 0.777 | ||
| N0 | 60 (61.86) | 325 (64.61) | |
| N1 | 11 (11.34) | 64 (12.72) | |
| N2 | 10 (10.31) | 50 (9.94) | |
| N3 | 16 (16.49) | 64 (12.72) | |
| Tumor size (cm) | 4.47 ± 3.23 | 4.08 ± 2.87 | 0.228 |
| Number of retrieved LNs | 37.79 ± 12.94 | 35.28 ± 14.20 | 0.094 |
| Number of metastatic LNs | 3.73 ± 10.15 | 2.66 ± 6.19 | 0.545 |
| Multiplicity | 0.782 | ||
| Single lesion | 94 (96.91) | 482 (95.83) | |
| Multiple lesions | 3 (3.09) | 21 (4.17) | |
| Lauren classification | < 0.001 | ||
| Intestinal type | 25 (25.77) | 277 (55.07) | |
| Diffuse type | 51 (52.58) | 112 (22.27) | |
| Mixed type | 15 (15.46) | 69 (13.72) | |
| Indeterminate type | 6 (6.19) | 45 (8.95) | |
| LV invasion | 24 (24.74) | 177 (35.19) | 0.046 |
| PN invasion | 33 (34.02) | 122 (24.25) | 0.044 |
| Extent of omentectomy | 0.916 | ||
| Total omentectomy | 37 (38.14) | 189 (37.57) | |
| Partial omentectomy | 60 (61.86) | 314 (62.43) | |
| Postoperative complications | 0.242 | ||
| No | 93 (95.88) | 482 (95.83) | |
| CDC I | 2 (2.06) | 3 (0.60) | |
| > CDC II | 2 (2.06) | 18 (3.58) | |
| In-hospital mortality | 0 (0.0) | 2 (0.40) | 1 |
| Adjuvant CTx | 44 (45.36) | 153 (30.42) | 0.004 |
Operative findings, including the extent of gastrectomy, LN dissection, and omentectomy, were comparable between the groups. Postoperative complication rates and in-hospital mortality were similar. Notably, despite comparable pathological staging, the use of adjuvant chemotherapy was significantly higher in the EOGC group than in the M-GC group (45.4% vs 30.4%, P = 0.004). The robustness of the IPTW adjustment was confirmed by SMDs of less than 0.1 for all adjusted baseline covariates.
The median follow-up duration was 67 months. In the entire cohort, the 5-year RFS was significantly higher in the EOGC group than in the M-GC group [80.74% vs 72.18%; hazard ratio (HR), 0.57; 95% confidence interval (CI): 0.360-0.890; P = 0.014]. The 5-year OS also tended to be higher in the EOGC group compared with the M-GC group (78.38% vs 75.33%; HR, 0.69; 95%CI: 0.461-1.033; P = 0.072), although this difference did not reach statistical significance. Patients with stage IV disease were excluded from RFS analyses because recurrence could not be clearly defined in this population.
After adjustment using IPTW, RFS and OS were significantly improved in the EOGC group. The IPTW-adjusted 5-year RFS was 81.36% in the EOGC group and 72.10% in the M-GC group (P = 0.021); the 5-year OS was 81.00% and 75.71%, respectively (P = 0.016) (Figure 2).
Stage-specific analyses of RFS were performed in patients with stage I-III disease. Across all stages, EOGC demonstrated consistently favorable RFS compared with M-GC, with a statistically significant difference observed in stage III disease (Figure 3 and Table 3). In contrast, stage-specific OS analyses did not show statistically significant diffe
| Unadjusted | IPTW-adjusted | ||||
| HR (95%CI) | P value | HR (95%CI) | P value | ||
| pStage I | M-GC | 1.00 | 0.064 | 1.00 | 0.234 |
| EOGC | 0.38 (0.14-1.06) | 0.60 (0.26-1.40) | |||
| pStage II | M-GC | 1.00 | 0.080 | 1.00 | 0.136 |
| EOGC | 0.47 (0.17-1.10) | 0.50 (0.20-1.25) | |||
| pStage III | M-GC | 1.00 | 0.043 | 1.00 | 0.032 |
| EOGC | 0.53 (0.29-0.98) | 0.50 (0.26-0.94) | |||
| Total population | M-GC | 1.00 | 0.014 | 1.00 | 0.021 |
| EOGC | 0.57 (0.36-0.89) | 0.50 (0.38-0.93) | |||
| Unadjusted | IPTW-adjusted | ||||
| HR (95%CI) | P value | HR (95%CI) | P value | ||
| pStage I | M-GC | 1.00 | 0.051 | 1.00 | 0.016 |
| EOGC | 0.31 (0.10-1.00) | 0.32 (0.10-1.03) | |||
| pStage II | M-GC | 1.00 | 0.095 | 1.00 | 0.225 |
| EOGC | 0.42 (1.48-1.16) | 0.55 (0.21-1.44) | |||
| pStage III | M-GC | 1.00 | 0.125 | 1.00 | 0.120 |
| EOGC | 0.62 (0.34-1.14) | 0.61 (0.32-1.14) | |||
| pStage IV | M-GC | 1.00 | 0.222 | 1.00 | 0.052 |
| EOGC | 0.60 (0.27-1.36) | 0.34 (0.11-1.01) | |||
| Total population | M-GC | 1.00 | 0.072 | 1.00 | 0.016 |
| EOGC | 0.69 (0.46-1.03) | 0.58 (0.37-0.90) | |||
In this study, we evaluated the clinicopathological characteristics and survival outcomes of EOGC using an evidence-based age cutoff of 50 years and a mid-aged comparison group to minimize confounding from advanced age and com
Recent population-based studies have highlighted a broader epidemiologic shift characterized by a rising incidence of cancer among younger patient cohorts across multiple cancer types[2]. Analyses based on large international cancer registries have demonstrated increasing incidence rate ratios for several malignancies in younger populations, whereas mortality trends have generally stabilized or declined for many cancer types at the population level[3]. These seemingly divergent patterns have been attributed not to reduced biological aggressiveness but rather to improvements in early detection, treatment strategies, and supportive care, particularly among younger patients who are more likely to tolerate intensive therapies[16]. Importantly, these trends vary substantially by cancer type, underscoring the need for cancer-specific evaluation. Within this context, EOGC should be considered as part of this wider oncologic phenomenon, in which pathological features traditionally regarded as aggressive do not necessarily translate into inferior clinical outcomes.
Cancer diagnosed at a younger age carries distinct clinical and psychosocial implications that extend beyond oncologic outcomes. Younger patients are more likely to face issues related to fertility preservation, long-term treatment-related toxicity, and psychosocial burden during a prolonged survivorship period[17-19]. Despite these unique considerations, oncologic research has traditionally focused on pediatric malignancies or cancers in older adults, with relatively limited attention to malignancies affecting young adult populations. As a result, the clinical characteristics and optimal management strategies for cancers diagnosed in younger adults remain incompletely defined. In this regard, a clearer understanding of EOGC is particularly important, as survival outcomes alone may not fully capture the long-term impact of the disease and its treatment in this population.
In the present study, patients with EOGC exhibited a higher proportion of diffuse-type histology and perineural invasion compared with those with M-GC, while pathological stage distribution and lymphovascular invasion did not differ significantly between the groups. Previous observational studies have similarly reported that gastric cancer diag
One plausible explanation for the favorable survival outcomes observed in patients with EOGC is their greater capacity to tolerate intensive multimodal treatment. Younger patients generally have fewer comorbidities and better performance status, which may allow for the delivery of standard-dose or full-course adjuvant chemotherapy. In our cohort, the use of adjuvant chemotherapy was more frequent in the EOGC group despite a similar stage distribution, suggesting a potential treatment-related contribution to improved outcomes. As shown in the Results, most patients with stage II or III disease in the EOGC group received adjuvant chemotherapy, whereas a smaller proportion of patients in the M-GC group with comparable stages underwent adjuvant treatment. This difference may be particularly relevant in stage III disease, where oxaliplatin-based regimens such as Capecitabine-Oxaliplatin are commonly recommended but may be omitted or dose-reduced in patients with substantial comorbidities in routine clinical practice[11]. In this context, younger patients with gastric cancer may derive greater benefit from adjuvant therapy, underscoring that biologically unfavorable or tradi
The favorable survival outcomes observed in patients with EOGC may be further explained by distinct biological mechanisms. Recent studies have suggested that the immune microenvironment in younger patients might be more “immune-hot”, characterized by higher levels of tumor-infiltrating lymphocytes and a more robust immune response compared to older patients[24]. Additionally, molecular profiling indicates that while EOGC is frequently associated with the genetically stable subtype and with CDH1 mutations, emerging research into pathways such as ferroptosis and tumor-associated macrophage modulation also hints at a unique therapeutic vulnerability in younger populations[25,26]. Although younger patients present with histologically aggressive tumors, these underlying biological traits, combined with their superior physiological reserve to tolerate full-dose multimodal therapy, may collectively contribute to an independent prognostic advantage.
Despite these findings, some limitations should be acknowledged. First, this was a retrospective analysis conducted at a single tertiary center with an exclusively Korean cohort, which may limit the generalizability of the results. Considering that unique Korean lifestyle factors, such as specific dietary habits involving pickled and salted foods, are closely associated with the risk of gastric cancer[27], further external validation in diverse, multi-ethnic cohorts is warranted to confirm the general validity of our results. Second, the study population was restricted to surgically treated patients; thus, very early-stage gastric cancers managed with endoscopic resection were not included. However, this design allowed a focused evaluation of patients for whom long-term oncologic outcomes and recurrence remain clinically relevant. Third, although IPTW was applied to minimize baseline imbalances, unmeasured confounders inherent to retrospective analyses cannot be completely excluded. Because this study was based on a pre-existing clinical registry, detailed information on lifestyle factors (e.g., smoking and dietary habits), socioeconomic status, and Helicobacter pylori infection status was not available. While these factors could potentially influence clinical outcomes, their inclusion as variables was limited by the retrospective nature of the data. Consequently, the potential impact of these unmeasured factors should be considered when interpreting our findings. Lastly, our study lacked detailed molecular characterization (e.g., MSI, HER2, or EBV status), as specific markers are not routinely captured in our surgical registry, particularly in stage I-III patients for whom they are not mandatory for standard clinical decision-making.
Nevertheless, by adopting an evidence-based age cutoff and a mid-aged comparison group to reduce confounding from advanced age and competing mortality, this study provides a clinically meaningful perspective on the prognosis of EOGC. Given the increasing incidence of gastric cancer in younger populations, future multicenter studies incorporating molecular profiling and long-term survivorship issues are warranted to further elucidate the distinct biology and optimal management strategies for this growing patient group.
This study demonstrates that EOGC, defined by an evidence-based age cutoff of 50 years, exhibits survival outcomes that are at least comparable to those of M-GC, despite a higher prevalence of diffuse-type histology. These findings indicate that biological features traditionally regarded as aggressive in younger patients do not inevitably result in poorer clinical outcomes, particularly when adequate surgical and adjuvant treatments are feasible. Clinicians should provide optimistic counseling and prioritize the delivery of standard radical surgery and active multimodal treatment, given the high treatment tolerance of this population. With the increasing incidence of gastric cancer among younger individuals, future multicenter studies incorporating molecular characterization and long-term survivorship considerations are warranted to refine risk stratification and optimize management strategies for this distinct patient population.
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