The incidence of Early-Onset Colorectal Cancer (EOCRC) has risen markedly in recent years, garnering widespread attention due to its distinctive clinical and biological features. However, systematic research on prognostic risk factors and long-term survival prediction for EOCRC patients undergoing postoperative chemotherapy remains scarce. This study seeks to pinpoint critical prognostic factors for EOCRC patients receiving postoperative chemotherapy and to devise a survival prediction tool employing a Nomogram model.

Patients diagnosed with EOCRC between 2010 and 2015, who underwent postoperative chemotherapy, were extracted from the SEER (Surveillance, Epidemiology, and End Results) database. Only those meeting the inclusion criteria were included. Univariate and multivariate Cox regression analyses were performed to determine independent risk factors influencing overall survival (OS). A Nomogram model was then developed using significant variables. The model's predictive accuracy and clinical utility were assessed through the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA).

A cohort of 9,205 patients was analyzed, with 6,445 randomly allocated to the training group and 2,760 to the validation group from the SEER database. Independent prognostic factors, including gender, race, marital status, primary tumor location, histological type, TNM stage, CEA levels, bone metastasis, liver metastasis, and lung metastasis, were identified through univariate and multivariate Cox regression analyses. A Nomogram model constructed from these factors yielded a C-index of 0.76 (0.75, 0.77) in the training group and 0.76 (0.75, 0.78) in the validation group, reflecting robust discriminative ability and consistency. The area under the curve (AUC) for predicting 1-year OS was calculated as 0.84 (0.81, 0.86) in the training group and 0.82 (0.78, 0.85) in the validation group. For 3-year OS, AUCs were recorded at 0.83 (0.82, 0.84) and 0.82 (0.80, 0.84), respectively, while for 5-year OS, AUCs reached 0.81 (0.80, 0.82) and 0.82 (0.80, 0.84). Calibration curves demonstrated close alignment between predicted and observed survival rates. Additionally, DCA affirmed the model's clinical decision-making value.

Prognostic risk factors for EOCRC patients receiving postoperative chemotherapy were systematically evaluated in this study, leading to the development of a Nomogram-based survival prediction model. This tool offers a robust scientific foundation for tailoring individualized treatment and guiding follow-up strategies.

The incidence of early-onset colorectal cancer (EoCRC), defined as CRC diagnosed at < 50 years of age, is increasing globally. However, only a few studies are reported from Japan, and the clinicopathological features of EoCRC in Japanese patients remain unknown.

We retrospectively investigated consecutive Japanese patients who were pathologically diagnosed with invasive CRC at our hospital from January 2015 to December 2021. Patients were categorized into those who were diagnosed with CRC at < 50 years (early-onset group) and ≥ 50 years (late-onset group) of age. We compared the clinicopathological findings between the two groups.

The analysis included 731 patients. EoCRC was diagnosed in 46 patients　(6.3% of all patients). Of them, 41.3% demonstrated a positive fecal immunochemical test (FIT) for CRC screening as a diagnostic opportunity, which was significantly higher than that in the late-onset group (p = 0.032). Rectal cancer was significantly more prevalent in the early-onset group compared to the late-onset group (45.7% vs. 26.4%, p < 001). No significant difference in the rate of clinical stage at presentation was found between the two groups. Furthermore, patients with positive FIT were more likely diagnosed at an earlier stage.

EoCRC among Japanese patients tends to occur on the rectum and is more frequently diagnosed with FIT screening compared to late-onset CRC. Patients with advanced stage were diagnosed by symptoms, indicating the usefulness of FIT screening in diagnosing EoCRC at an early stage.

The incidence of early-onset colorectal cancer is increasing, but in Europe this growth shows a heterogeneous pattern in different countries and regions.

Patients from six countries who participated in the Global Early-Onset COlorectal Cancer DatabasE (GEOCODE)-Europe group were included. The inclusion criteria were patients with colorectal adenocarcinoma diagnosed between 18 and 49 years of age, between January 2010 and December 2017, with at least 3 years of follow-up. Patients with inherited colorectal cancer syndromes were excluded.

A total of 851 patients were included with almost equal sex distribution, most were diagnosed at age 39 years or older and 42% of patients were overweight or obese. Diagnoses were predominantly at later stages (62.5% stage III-IV) and tumours were predominantly located in the distal colon (76.9% left colon and rectum). Comparative analysis between countries demonstrated that the UK had a younger age at diagnosis and the Italian cohort had a higher prevalence of being overweight or obese. Patients from Luxembourg had more advanced stage diagnoses and those from The Netherlands had more polyps. Patients from the UK had a greater family history of colorectal cancer. Comparison of Mediterranean versus non-Mediterranean countries showed significant differences in the age at diagnosis and body mass index. The prevalence of early-onset colorectal cancer over the age of 40 years in Mediterranean versus non-Mediterranean countries was 71.4% versus 62.1% (P = 0.002), and early-onset colorectal cancer was diagnosed at a more advanced stage in Mediterranean countries versus non-Mediterranean countries (65.3% versus 54.7%; P = 0.033). Family history of colorectal cancer in a first-degree relative was more common in non-Mediterranean versus Mediterranean countries (19.1% versus 11.4%; P < 0.001).

This study highlights significant geographical disparities in the clinical, pathological and familial features of early-onset colorectal cancer across European countries.

The incidence of early-onset colorectal cancer among the young (<50 years) has been reported to have risen in last decades. This retrospective study aimed to investigate the characteristics of early-onset rectal cancers (EO-RCs) and potential changes in proportion of EO-RCs, and further to report the mortality and recurrence rates of EO-RCs.

In the years 2007-2021, 2557 rectal cancer (RC) patients were operated in Helsinki University Hospital and of them 147 were 18-49 years old. Cumulative overall survival (OS), disease-specific survival, and disease-free survival were calculated using the Kaplan-Meier analysis.

The percentual amount of the EO-RCs varied between 2.5% and 11.3% annually and there was no perceivable trend. Majority were adenocarcinomas (98.7%), of which 8.8% were mucinous. Predisposing factors such as Lynch syndrome, polyposis, or ulcerative colitis were seen in 26 patients (17.7%) and in 10 of 22 patients (45.5%) under 35 years. The cumulative 5-year OS was 91.9% in stage I, 93.3% in stage II, 86.7% in stage III, and 50.0% in stage IV disease. Metastatic recurrence was found in 22 cases (18.4%) and local recurrence in 8 patients (5.4%) and 6 patients had both.

In our cohort of 147 EO-RC patients, OS was good and the clinical course did not seem to differ much from the course of RC in general population.

Colorectal cancer (CRC) is the third-most common cancer globally and a leading cause of cancer-related deaths. While the prognostic and predictive roles of RAS mutations in advanced CRC are well-established, their significance in early-stage CRC remains a topic of debate. Studies have been conducted for many years on clinical and pathological parameters that may be associated with RAS mutation, and there are inconsistent results in this regard. Currently, the only biomarker used in early-stage CRC is microsatellite status. KRAS mutations are detected in 40-50% of patients with colorectal cancer. RAS activating mutations cause loss of EGFR regulation by acting on the RAS/RAF/MAPK signaling pathways. In advanced colorectal cancer, these mechanisms cause a decrease in the effectiveness of EGFR inhibitors. However, studies on patients with early-stage colorectal cancer have inconsistent results. This review highlights the prognostic and clinical significance of KRAS mutations in early-stage CRC, particularly in MSS tumors. In the MSS group, KRAS mutations were associated with shorter TTR and OS compared to DWT patients. In contrast, in the MSI-H group, KRAS mutations showed no prognostic effect in TTR and OS. However. KRAS mutations were associated with shorter SAR in both MSI-H and MSS groups of patients. The findings underscore the need for routine molecular profiling, including KRAS and MSI status, to refine risk stratification and guide adjuvant therapy decisions. Further studies are warranted to explore targeted therapeutic approaches for KRAS-mutant CRC in the adjuvant setting.

Reports indicate a worldwide increase in the incidence of Early-Onset Colorectal Carcinoma (EOCRC) (<50 years old). In an effort to understand the different modes of pathogenesis in early-onset CRC, colorectal tumors from EOCRC (<50 years old) and Late-Onset patients (LOCRC; >50 years old) were screened to eliminate microsatellite instability (MSI), nuclear β-catenin, and APC mutations, as these are known canonical factors in CRC pathogenesis. Small-RNA sequencing followed by comparative analysis revealed differential expression of 23 miRNAs (microRNAs) specific to EOCRC and 11 miRNAs specific to LOCRC. We validated the top 10 EOCRC DEMs in TCGA-COAD and TCGA-READ cohorts, followed by validation in additional EOCRC and LOCRC cohorts. Our integrated analysis revealed upregulation of hsa-miR-1247-3p and hsa-miR-148a-3p and downregulation of hsa-miR-326 between the two subsets. Experimentally validated targets of the above miRNAs were compared with differentially expressed genes in the TCGA dataset to identify targets with physiological significance in EOCRC development. Our analysis revealed metabolic reprogramming, downregulation of anoikis-regulating pathways, and changes in tissue morphogenesis, potentially leading to anchorage-independent growth and progression of epithelial-mesenchymal transition (EMT). Upregulated targets include proteins present in the basal part of intestinal epithelial cells and genes whose expression is known to correlate with invasion and poor prognosis.

Early onset colorectal cancer (EO-CRC) is increasing. We investigated the risk factors for ER-CRC compared to late onset colorectal cancer (LO-CRC). CRC patients between the years 1999 and 2021 were retrospectively evaluated. Data regarding demographics, comorbidities, malignancies, and mortality were collected. Data were retrieved using the MdClone platform from a large Health Maintenance Organization. The cohort was subdivided into EO-CRC (age ≤ 50 years) and LO-CRC (age ≥ 51 years) groups. 61,679 patients diagnosed with CRC were included in our analysis, 30,456 (49.4%) males, and 4891 (7.9%) Arabs, with an average age at diagnosis of 70.1 ± 13.1 years. 5561 (9%) patients were included in the EO-CRC group. Over the last decades, higher rates of EO-CRC were diagnosed compared to the previous decade, 9.8% vs 8.3%, p < 0.001. A higher percentage of EO-CRC patients were females (52.8% vs 50.4%), had a family history of CRC (9.9% vs 5.5%), were Arabs (18.7% vs 6.9%), and were smokers (32.7% vs 30.2%) compared to LO-CRC patients. Significantly lower rates of comorbidities such as ischemic heart disease, diabetes mellitus, hypertension, obesity, and iron deficiency anemia were found among EO-CRC patients, with a lower all-cause mortality (27.7% vs 63.1%, p < 0.001). 348 (6.3%) of the EO-CRC patients had another Lynch-related cancer until age 50 years compared to 45 (0.1%) at the LO-CRC. Young individuals with increased risk for CRC need special consideration and should be referred early for screening and endoscopic investigation, particularly those with a family history of CRC, smokers, and those of Arab ethnicity.

Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades.

Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years).

EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs. 59%), and advanced-stage disease. Molecular analyses revealed differences in mutation patterns, with EOCRC having higher frequencies of TP53 (74% vs. 68%, p < 0.01) and SMAD4 (17% vs. 14%, p = 0.015), while BRAF (5% vs. 11%, p < 0.001) and NOTCH1 (2.7% vs. 4.1%, p = 0.01) mutations were more prevalent in LOCRC. Stratification by tumor site and MSI status highlighted significant location- and age-specific molecular differences, such as increased KRAS and CTNNB1 mutations in right-sided EOCRC and higher BRAF prevalence in MSI-H LOCRC (47% vs. 6.7%, p < 0.001). Additionally, co-occurrence analysis revealed unique mutational networks in EOCRC MSS, including significant co-occurrences of FBXW7 with NOTCH3, RB1, and PIK3R1.

This study highlights the significance of age-specific molecular profiling, offering insights into the unique biology of EOCRC and potential clinical applications.

Impact of rectal tumour location on risk of lymph node metastases (LNM) and recurrence in early RC is poorly studied and elusive. Tumour location as a prognostic factor may contribute to optimise management of early RC in the future. The aim of this study was to investigate rectal tumour location as an independent predictor of oncologic outcome in early rectal cancer (RC).

Retrospective multicentre national cohort study on prospectively collected data on all patients with T1-T2 RC, undergoing surgical resection between 2009 and 2021. Tumour location was categorised as distal (0-5 cm), mid (5-10 cm), and proximal (10-16 cm), measured from the anal verge.

Incidence of LNM in the 2424 included T1-T2 RC patients was 18.2%, 17.3% and 21.6% for distal, mid and proximal tumours, respectively. Recurrence was detected in 130 (7.6%) out of 1705 patients available for recurrence analyses (60-month median follow-up). Incidence of recurrence was twice as high in distal (11.4%) compared to proximal (5.6%) tumours and was 8.3% in mid located tumours. Distal (HR 2.051, CI 1.248-3.371, P < 0.05) and mid (HR 1.592, CI 1.061-2.388, P < 0.05) tumour location were significant risk factors of recurrence in uni- and multivariate Cox regression analyses.

This study shows that tumour location significantly affects incidence of recurrence in early RC, with an increasing risk for mid and especially distal location, found to be a predominant risk factor of recurrence. Our findings stress the need for an increased awareness on differences in oncologic outcome related to tumour location in early RC.

Despite a reduction of both incidence and mortality from CRC, recent studies have shown an increase in the incidence of early-onset CRC (EO-CRC). Data on this setting are limited. The aim of our study was to evaluate the clinical and molecular profiles of metastatic EO-CRC patients in order to identify differences compared to a late-onset CRC (LO-CRC) control group.

We retrospectively collected data from 1272 metastatic colorectal cancers from 5 different Italian Institutions. The main objective was to the evaluate clinical outcome for EO-CRC patients in comparison to patients included in the control group.

In the overall population, mOS was 34,7 in EO-CRC pts vs 43,0 months (mo) (p < 0,0001). In the RAS/BRAF mutated subgroup mOS in EO-CRC pts was 30,3 vs 34,0 mo (p = 0,0156). In RAS/BRAF wild-type EO-CRC mOS was 43,0 vs 50,0 mo (p = 0,0290). mPFS was 11,0 in EO-CRC pts vs 14,0 mo (p < 0,0001).

Findings indicate a general worse prognosis for patients with early-onset colorectal cancer compared to late-onset patients. Interestingly this seems to occur regardless of the molecular status. These observations might have a considerable impact on clinical practice and research.

The risk of developing a second primary malignancy differs among colorectal cancer patients in different age groups. This study aimed to investigate the differences in prognosis and clinicopathological features of patients with early-onset colorectal cancer and late-onset colorectal cancer who developed second primary malignancies.

The study included 15 489 patients who underwent surgery for colorectal cancer at Fudan University Shanghai Cancer Center between January 2008 and December 2018. Data pertaining to these patients were derived from the database.

A total of 680 (4.5%) patients subsequently developed a second primary malignancy. Considering death as a competing event, the 10-year cumulative risk of second primary malignancy for early-onset colorectal cancer was 5.3%, compared with 7.3% for late-onset colorectal cancer. Cox analysis showed that late-onset colorectal cancer, colon cancer, smaller tumor size, and fewer tumor nodules without residual lymph node structure, chemotherapy, and radiotherapy were independent risk factors for second primary malignancy. In our patient cohort, early-onset colorectal cancer was associated with better prognosis compared to late-onset colorectal cancer, for both overall survival and second primary malignancy-free survival. In addition, there was insufficient evidence that early-onset colorectal cancer also affected prognosis after the occurrence of second primary malignancies.

The risk of early-onset colorectal cancer subsequently developing second primary malignancy was significantly lower than late-onset colorectal cancer, and the second primary malignancies of early-onset colorectal cancer were more likely to be colorectal cancer. Overall survival and second primary malignancy-free survival of early-onset colorectal cancer were consistently better than late-onset colorectal cancer.

Early onset Colorectal Cancer (EOCRC), defined as those diagnosed under the age of 50, has been increasing rapidly since 1970. UK data on EOCRC are currently limited and better understanding of the condition is needed.

A single-center retrospective study of patients with EOCRC treated over 9 years (2013-2021) at a large UK cancer center was performed. Clinicopathological features, risk factors, molecular drivers, treatment, and survival were analyzed.

In total, 203 patients were included. A significant increase in cases was reported from 2018-2019 (n = 33) to 2020-2021 (n = 118). Sporadic EOCRC accounted for 70% of cases and left-sided tumors represented 70.9% (n = 144). Median duration of symptoms was 3 months, while 52.7% of the patients had de-novo metastatic disease. Progression-free survival after first-line chemotherapy was 6 months (95% CI, 4.85-7.15) and median overall survival (OS) was 38 months (95% CI, 32.86-43.14). In the advanced setting, left-sided primary tumors were associated with a median OS benefit of 14 months over right-sided primaries (28 vs 14 months, P = .009). Finally, primary tumor resection was associated with median OS benefit of 21 months compared with in situ tumors (38 vs 17 months, P < .001).

The incidence of EOCRC is increasing, and survival outcomes remain modest. Raising public awareness and lowering the age for colorectal cancer screening are directions that could improve EOCRC clinical outcomes. There is also a need for large prospective studies to improve the understanding of the nature of EOCRC and the best therapeutic approaches.

Recent studies have shown an increase in the prevalence of early-onset colorectal cancer (CRC) in people aged 20-49 compared to those aged 50-74, with a more rapid increase in the younger age groups. Poorly differentiated, left-sided, and rectal tumors were more common in young adults than in older adult CRC patients. We aimed to improve the understanding of early-onset CRC and to guide primary care physicians on strategies to mitigate its impact.

Adult patients with CRC identified within 2015-2022 were recruited and divided into young adult-onset (CRC identified at age ≤49 years) and older adult-onset (CRC identified at age ≥50 years). Clinical data were retrieved from electronic medical records, then analyzed. Multivariable analyses were performed to predict the CRC prognosis in both age groups.

The study cohort had 530 patients categorized into young adult (n=98; 18.5%) and older adult (n=432; 81.5%). Higher proportions of family histories of CRC, other malignancies, and inflammatory bowel disease in the young adult group were observed (P<0.05). Gastrointestinal symptoms mainly abdominal pain and nausea were more often identified in the young adults. Mucinous adenocarcinoma, signet ring cells, and poorly differentiated tumors were higher in the young adults (P<0.05). Lymphovascular invasion was an independent predictor for advanced stage CRC (AOR 8.638, 95%CI 2.152-34.673, P=0.002 for young adults and AOR 21.757, 95%CI 10.025-47.219, P=0.001 for older adults). Further, the mucinous (AOR 3.727, 95%CI 1.937-7.173, P=0.001 for young adults and AOR 3.534, 95%CI 1.698-7.354, P=0.001 for older adults) and lymphovascular invasion (AOR 3.371, 95%CI 2.107-5.393, P=0.001 for young adults and AOR 3.246, 95%CI 1.910-5.517, P=0.001 for older adults) were independent predictors for recurrence/late metastasis in both age groups.

We recommended to raise awareness among healthcare providers of the importance of lowering the threshold of suspicion in young people presenting with worrisome gastrointestinal symptoms. Our findings suggested the importance of reconsidering the current CRC screening guidelines to lower the threshold of the recommended starting age.

Colorectal cancer (CRC) represents a significant health burden worldwide, with a notable increase in early-onset colorectal cancer (EOCRC) cases, defined as those diagnosed before the age of 50 years.

Using data from Taiwan's national cancer registry and a retrospective cohort from Chang Gung Memorial Hospital, this study analyzed CRC cases diagnosed between 2008 and 2019. The analysis compared the EOCRC and late-onset CRC (LOCRC) groups in terms of clinicopathological characteristics, pre-diagnostic symptoms, and survival outcomes.

The analysis revealed a continuous increase in the annual incidence of EOCRC, with colon cancer and rectal cancer rising by 3.2 % and 3.3 %, respectively. Patients with EOCRC presented with more aggressive disease characteristics, such as signet-ring cell adenocarcinoma, mucinous adenocarcinoma, and poorly differentiated grade. Advanced stages at diagnosis, stages III and IV, were more common with EOCRC (62.4 %) than with LOCRC (50.3 %). Patients with EOCRC reported rectal bleeding, changes in bowel habits, and abdominal pain more frequently than those in the LOCRC group. There is a strong association between stool-related symptoms and left-sided CRC. Despite similar surgical outcomes, the 5-year cancer-specific survival rate of patients with stage IV EOCRC was significantly lower than that of patients with LOCRC (32.8 % vs. 51.9 %, p = 0.012).

This study highlights a persistent rise in the incidence of EOCRC, with patients presenting with more aggressive disease and experiencing inferior survival. These findings underscore the importance of heightened awareness and early detection strategies for CRC, especially in younger populations, to improve the prognosis.

The onset of colorectal cancer (CRC) in patients younger than 50 continues to rapidly increase. This study highlights the epidemiologic changes, risk factors, clinical characteristics, and molecular profiles prevalent in early onset CRC patients, and identifies key areas for future research. It has been noted that only a small fraction of early onset CRC cases is attributed to known hereditary mutations and fit the canonical pathway of late-onset colorectal cancer development. To highlight this, we review the genetic and epigenetic modifications specific to early onset CRC. We also discuss the synergetic effect of single-nucleotide polymorphisms and environmental factors on the early onset of CRC. Additionally, we discuss the potential of noninvasive biomarker assays to enhance early detection, screening, diagnosis, and prognostic outcome predictions.

Colorectal cancer (CRC) is a major global health concern, with a rising incidence in young individuals. Early-onset CRC displays unique clinicopathological and molecular characteristics, necessitating a closer examination of prognosis, particularly in the context of adjuvant chemotherapy. This study aimed to investigate the prognosis of early-onset CRC patients (< 50 years) diagnosed at stage II/III compared to older counterparts, utilizing propensity score matching to minimize heterogeneity.

A retrospective analysis of 3324 stage II/III CRC patients aged < 70 years was conducted, focusing on age-based subgroups (< 50 vs. ≥ 50 years). Propensity score matching balanced clinical characteristics. Relapse-free survival (RFS) and overall survival (OS) were analyzed.

In stage II CRC, age of onset did not impact prognosis after adjuvant chemotherapy, with no significant differences in RFS (5-year RFS rates: 80% in both groups, p = 0.98) and OS (5-year OS rates: 96% vs. 92%, p = 0.17). In stage III, a trend suggested slightly poorer OS in patients aged < 50 years than those ≥ 50 years (5-year OS rates: 85% vs. 88%, p = 0.077). However, in a propensity score-matched cohort, age-dependent differences were attenuated (5-year OS rates: 85% vs. 88%, p = 0.32).

In the context of stage II/III CRC patients receiving adjuvant chemotherapy, age was not an independent predictor of prognosis. Age alone should not be the sole factor guiding treatment decisions.

Colorectal cancer that occurs before age of 50 is defined as Early-Onset Colorectal Cancer (EOCRC). Its incidence has worryingly increased since the late 90 s and is expected to keep rising in the next future, despite Late-Onset CRC (LOCRC) is decreasing worldwide. Because of this, there is an urgent need to better understand this subset of patients in order to give them the best treatment possible. However, most of the literature is retrospective and often discordant. In this review, we aim to provide a general overview of the issue, endeavoring to highlight the current available knowledge. We decided to move from the beginning, investigating risk factors and inheritance, passing through diagnosis and clinical aspects, and to conclude with the translational part, focusing on the biology of the tumor. However, lot of questions remain open, including screening age and prognosis. Indeed, young patients tend to be treated more aggressively, even if a survival benefit has not been proven yet. Every clinician should be aware of the best practice for young people, and more translational studies are awaited in order to clarify is EOCRC represents a distinct biological entity.

In recent years, the overall incidence of gastric cancer has decreased. However, the incidence of gastric signet ring cell carcinoma (SRCC) is still increasing year by year. Compared with other subtypes (non-SRCC) such as adenocarcinoma, SRCC usually exhibits a more aggressive biological behavior. Therefore, studying the prognostic differences and factors associated with SRCC is essential to improve the accuracy of diagnosis and prognosis. The purpose of this study was to investigate the prognostic factors influencing the prognosis of patients with SRCC and to develop personalized treatments for different subgroups of patients.

The data on gastric SRCC patients and gastric adenocarcinoma (AC) patients from 1992 to 2020 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The data of gastric SRCC as the external validation group was reviewed from the First Affiliated Hospital of Soochow University. The overall survival (OS) and cancer specific survival (CSS) at 1 and 2 years were predicted for SRCC patients by constructing prognostic nomograms. A series of validation methods, including Akaike information criterion (AIC), decision curve analysis (DCA), calibration curve analysis, the concordance index (C-index) and the area under the receiver operating characteristic (AUC) curve, were used to verify the accuracy and reliability of the models.

In all, 549 patients with SRCC were included after propensity score matching (PSM). Multivariate Cox regression analysis showed that T stage, N stage, M stage and surgical approach were independent risk factors affecting the prognosis of SRCC patients. A prognostic nomogram was constructed and validated as an accurate model for SRCC patients after scoring by receiver operating characteristic curve (ROC) curves and calibration plots. The patients were further divided into high-risk and low-risk groups, and the Kaplan-Meier curves showed that SRCC patients in the low-risk group could receive only surgery without chemotherapy, while chemotherapy plus surgery was a better option for SRCC patients in the high-risk group.

The prognosis for SRCC was less favorable than that of AC in terms of CSS. The nomograms were developed and validated to predict OS and CSS in patients with SRCC, helping in developing appropriate individualized treatment schedules.

The incidence of colorectal cancer (CRC) among individuals younger than age 50 (early-onset CRC [EOCRC]) has substantially increased, and yet the etiology and molecular mechanisms underlying this alarming rise remain unclear. We compared tumor-associated T-cell repertoires between EOCRC and average-onset CRC (AOCRC) to uncover potentially unique immune microenvironment-related features by age of onset. Our discovery cohort included 242 patients who underwent surgical resection at Cleveland Clinic from 2000 to 2020. EOCRC was defined as younger than age 50 years at diagnosis (N = 126) and AOCRC as 60 years of age or older (N = 116). T-cell receptor (TCR) abundance and clonality were measured by immunosequencing of tumors. Logistic regression models were used to evaluate the associations between TCR repertoire features and age of onset, adjusting for sex, race, tumor location, and stage. Findings were replicated in 152 EOCRC and 1984 AOCRC cases from the Molecular Epidemiology of Colorectal Cancer Study. EOCRC tumors had significantly higher TCR diversity compared with AOCRC tumors in the discovery cohort (odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.32 to 0.61, P < .0001). This association was also observed in the replication cohort (OR = 0.74, 95% CI = 0.62 to 0.89, P = .0013). No significant differences in TCR abundance were observed between EOCRC and AOCRC in either cohort. Higher TCR diversity, suggesting a more diverse intratumoral T-cell response, is more frequently observed in EOCRC than AOCRC. Further studies are warranted to investigate the role of T-cell diversity and the adaptive immune response more broadly in the etiology and outcomes of EOCRC.

Early-onset rectal cancer (EORC) is characterized by a unique disease process with different clinicopathological features compared with late-onset rectal cancer (LORC). Research on the risk of recurrence in EORC patients, however, is limited. We aim to develop a predictive model to accurately predict EORC recurrence risk.

Rectal cancer patients who underwent radical surgery and T2-weighted imaging and diffusion-weighted imaging magnetic resonance imaging (MRI) were retrospectively enrolled from three medical institutions from November 2012 to November 2018. Differences in clinicopathological characteristics between EORC and LORC were compared. Five prediction models for disease-free survival were constructed based on clinicopathological variables and five radiomic features from pretreatment MRI of the EORC. A fixed cut-off value calculated in the training set was used to stratify EORC patients into high-risk and low-risk groups of post-operative recurrence. Model performance was evaluated by concordance index (C-index) and receiver operating characteristic curve.

A total of 264 EORC patients (median age, 43 years, 163 males) and 778 LORC patients (median age, 62 years, 520 males) were enrolled. Pretreatment positive carcinoembryonic antigen [hazard ratio (HR) = 2.84, P = 0.006], pathological positive lymph node status (pN positive) [HR = 2.86, P = 0.011] and MRI-based radiomics score [HR = 2.72, P < 0.001] are independent risk factors for disease-free survival in EORC patients. The EORC-ClinPathRadiom model, constructed by integrating the clinicopathological characteristics and MRI-based radiomics features of EORC, showed C-index of 0.82, 0.82, and 0.81 in the training, internal, and external test sets, respectively. This model effectively stratified EORC patients into high risk and low risk of recurrence (HRs for the training, internal, and external test sets were 8.96, 6.81, and 7.46, respectively).

The EORC-ClinPathRadiom model can effectively predict and stratify the risk of post-operative recurrence in EORC patients.

Background and objective: Colorectal cancer (CRC) is the leading cause of mortality in Spain, with screening programs, such as the faecal occult blood test and colonoscopy, having shown effectiveness in reducing CRC incidence and mortality. Despite these advancements, CRC screening uptake remains low in Spain, highlighting the need for studies comparing outcomes between screening-diagnosed and symptom-diagnosed patients to better understand the impact on overall survival and to quantify the clinical benefit in prognosis at diagnosis and at the end of follow-up. Methods: We conducted a retrospective cohort study with the following objectives: to compare stage at diagnosis, all-cause mortality, and disease-specific mortality among people diagnosed with CRC based on screening and based on symptoms; to identify the risk factors associated with mortality in this population; and to evaluate the effectiveness of screening on survival and early detection. Our study included people diagnosed with CRC in the public hospital of Elda (Spain) from 2014 to 2018; follow-up was until 2023 or death. Our primary outcome was all-cause mortality, which we analysed using Kaplan-Meier curves. We also investigated CRC-specific mortality and other-cause mortality. Results: Our sample included 315 people (186 with symptom-based diagnoses, 129 with screening-based diagnoses). The mean length of follow-up was 62.8 months. The screening group had a higher prevalence of a family history of CRC (p = 0.008), a distal tumour location (p = 0.002), and a cancer stage of 0 or I (p < 0.001). The symptoms group had a higher prevalence of a proximal CRC (p = 0.002), other chronic diseases (p < 0.001), and stages II, III, and IV (p < 0.001). Two variables were associated with mortality: stage IV at diagnosis and previous cancers. People with a symptom-based diagnosis had a higher prevalence of stage IV at diagnosis and a higher cumulative incidence of CRC mortality and all-cause mortality at the end of follow-up (p < 0.05). The Kaplan-Meier curves also showed a higher rate of all-cause mortality in the symptoms group throughout the follow-up. Conclusion: CRC screening enables an earlier diagnosis and improves survival. These findings support public health policies that promote accessible and effective screening.

There has been a global increase in early-onset colorectal cancer (EOCRC), yet there has been very limited exploration of its impact in Indonesia. This study aimed to determine the clinicopathologic characteristics and the overall survival (OS) of EOCRC compared with those of average-onset colorectal cancer (AOCRC).

Medical records were retrospectively reviewed from all patients presenting with colorectal cancer (CRC) at Dr Sardjito General Hospital (Yogyakarta, Indonesia) between 2016 and 2019. Sociodemographic, clinicopathologic, and treatment variables were extracted. t Tests were used to compare characteristics of EOCRC and AOCRC patient groups. The Cox proportional hazards regression model was used to analyze age and other potential prognostic factors.

The total population (N = 1,276) comprised EOCRC (n = 149; 11.7%) and AOCRC (n = 1,127; 88.3%) patients. EOCRC patients were more likely to have a higher education level, be single, have out-of-pocket insurance, be underweight, and have signet ring histology (all P values <.05), compared with AOCRC patients. EOCRC and AOCRC groups had a comparable estimated 5-year OS of 34.2% and 36.9%, respectively. In multivariable analyses, performance status (Eastern Cooperative Oncology Group), hemoglobin level, cancer stage, and treatment intention were independent prognostic factors for OS (all P values <.05).

To our knowledge, this first major study of EOCRC in Indonesia highlights its role in the overall burden of CRC and its connection with social determinants of health. Patients with EOCRC are more commonly underweight and generally have a higher proportion of signet ring histology than AOCRC, yet OS in both groups is similar. Future research is required to identify risk factors to inform the content and focus of public health education activities, alongside delineating the biology and causes of early and average onset of the disease.

The incidence of colorectal carcinoma (CRC) is increasing among individuals younger than 50, and some studies suggest the presence of differences in CRC among old and young individuals regarding clinical and histopathological features. The aim of this study was to compare clinicopathological features, mismatch repair protein status, and expression of certain immunohistochemical stains between young and old groups. The study included 180 cases and found significant histological and immunohistochemical differences between the two groups. CRC in the young tends to be more right-sided and has a higher percentage of dMMR proteins, but less expression of p53 mutations. These features are commoner in Lynch syndrome, and more investigations to study the relationship between young-onset CRC and hereditary syndromes are needed. Young-onset CRC also tends to show higher expression of tumor cell PD-L1, which is an expected finding, as dMMR cases are more likely to be immunogenic. Two other significant differences are the higher percentage of mucinous carcinoma and the higher tumor grade in young-onset CRC. These two features suggest a more advanced disease with possibly worse outcomes; however, there is no difference in disease stage between the two age groups.

The incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019.

Data on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0-4, 5-9, 10-14 and 15-19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC.

The global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0-4, 5-9, 10-14 and 15-19 years were also associated with the incidences, particularly for the exposures at ages 15-19 years.

The global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.

Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP).

We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years).

Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP.

Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted.

Early-onset colorectal cancer (EO-CRC) is defined as colorectal cancer diagnosed before the age of 50 years, and its incidence has been increasing over the last decade, now accounting for 10% of all new CRC diagnoses. Average-onset colorectal cancer (AO-CRC) has shown a steady decline in its incidence and related mortality over the past 20 years. The disparities in outcomes and overall survival (OS) between EO-CRC and AO-CRC are controversial. Our study compared OS and cause-specific survival (CSS) between metastatic EO-CRC (mEO-CRC) and metastatic AO-CRC (mAO-CRC) and identified the associated factors.

Data on patient characteristics, tumor characteristics, incidence, and mortality were obtained from the SEER database from 2010 to 2020. We identified 23,278 individuals aged > 18 years with a confirmed diagnosis of all histological subtypes of metastatic CRC (M1 on TNM stage) using ICD-O-3 site codes. mEO-CRC and mAO-CRC were compared. OS distributions and CCS were analyzed using the Kaplan-Meier method and log-rank test to assess differences. A Cox regression model was used to assess the associations between variables.

mEO-CRC constituted 17.79% of the cases, whereas 82.21% had mAO-CRC. Most patients with mEO-CRC were 45-49 years old (47.66%), male (52.16%) and White (72.57%) and had adenocarcinoma histology (87.30%). Left colon tumors were most prevalent in both groups (40.26%) but were more prevalent in mEO-CRC patients than in mAO-CRC patients (49.63% vs. 38.23%, p < 0.001). Patients with mEO-CRC had higher OS (p < 0.001) and CSS (p < 0.001) than those with mAO-CRC. Patients with mEO-CRC also had significantly better median overall survival (30 months vs. 18 months, p < 0.001). The factors associated with worse OS included mAO-CRC (p < 0.001), mucinous adenocarcinoma (p < 0.001), male sex (p = 0.003), and a lack of surgical intervention (p < 0.001).

Most patients with mEO-CRC fall within the range of 45 to 49 years of age. Patients with mEO-CRC were more likely to receive cancer-directed therapy (including chemotherapy and radiotherapy) and had better OS and CSS than those with mAO-CRC. This is likely attributable to the better performance status, fewer comorbidities, and better tolerance to cancer-directed therapy in mEO-CRC patients. The factors associated with worse OS and CSS were age > 50 years, mucinous adenocarcinoma, male sex, and no surgical treatment.

Metastatic colorectal cancer requires a multidisciplinary and individualized approach. Herein, we reported the case of a young woman diagnosed with metastatic rectal cancer who received an individualized multimodal treatment strategy that resulted in a remarkable survival. There were several particular aspects of this case, such as the early onset of the disease, the successful use of conversion therapy, the application of liquid biopsy to guide treatment, and the specific nature of the bone metastasis. To offer more insights for navigating such challenges in patients with metastatic colorectal cancer, we have conducted a literature review to find more data related to the particularities of this case. The incidence of early onset colorectal cancer is on the rise. Data suggests that it differs from older-onset colorectal cancer in terms of its pathological, epidemiological, anatomical, metabolic, and biological characteristics. Conversion therapy and surgical intervention provide an opportunity for cure and improve outcomes in metastatic colorectal cancer. It is important to approach each case individually, as every patient with limited liver disease should be considered as a candidate for secondary resection. Moreover, liquid biopsy has an important role in the individualized management of metastatic colorectal cancer patients, as it offers additional information for treatment decisions.

Although colorectal cancer (CRC) remains the second leading cause of cancer-related death in the United States, the overall incidence and mortality from the disease have declined in recent decades. In contrast, there has been a steady increase in the incidence of CRC in individuals under 50 years of age. Hereditary syndromes contribute disproportionately to early onset CRC (EOCRC). These include microsatellite instability high (MSI+) tumors arising in patients with Lynch Syndrome. However, most EOCRCs are not associated with familial syndromes or MSI+ genotypes. Comprehensive genomic profiling has provided the basis of improved more personalized treatments for older CRC patients. However, less is known about the basis of sporadic EOCRC. To define the genomic landscape of EOCRC we used DNA content flow sorting to isolate diploid and aneuploid tumor fractions from 21 non-hereditary cases. We then generated whole exome mutational profiles for each case and whole genome copy number, telomere length, and EGFR immunohistochemistry (IHC) analyses on subsets of samples. These results discriminate the molecular features of diploid and aneuploid EOCRC and provide a basis for larger population-based studies and the development of effective strategies to monitor and treat this emerging disease.

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of CRC across different populations, most probably due to differences in exposure to lifestyle and environmental factors related to CRC. Prevention is the most effective method for controlling CRC. Primary prevention includes determining and avoiding modifiable risk factors (e.g., alcohol consumption, smoking, and dietary factors) as well as increasing protective factors (e.g., physical activity, aspirin). Further studies, especially randomized, controlled trials, are needed to clarify the association between CRC incidence and exposure to different risk factors or protective factors. Detection and removal of precancerous colorectal lesions is also an effective strategy for controlling CRC. Multiple factors, both at the individual and community levels (e.g., patient preferences, availability of screening modalities, costs, benefits, and adverse events), should be taken into account in designing and implementing CRC screening programs. Health policymakers should consider the best decision in identifying the starting age and selection of the most effective screening strategies for the target population. This review aims to present updated evidence on the epidemiology, risk factors, and prevention of CRC.

While advances in screening have resulted in declining rates of colorectal cancer (CRC) among adults ≥50 years of age since the mid-2000s, the incidence of early-onset CRC (EOCRC) has steadily increased over the last decade. This increase is not fully accounted for by hereditary factors, and the hypothesis that a sedentary lifestyle and obesity are the primary culprits is not fully supported by recent reports indicating that many affected individuals lead active lifestyles, maintain normal weight, and are otherwise healthy. Attention has shifted toward dietary patterns, notably the consumption of processed and ultra-processed foods found in Western diets, which are suspected of disrupting the gut microbiome balance that potentially leads to EOCRC. The impact of antibiotic use on the gut microbiome is also posited as a contributing factor, given its rising prevalence in medical and agricultural practices. We propose that a paradigm shift is necessary for EOCRC research, moving beyond metabolic factors to a broader exploration of dietary and microbial influences. Future research must prioritize understanding the relationship between dietary habits, particularly processed food intake, antibiotic exposure, and gut microbiome dynamics, to unravel the complex etiology of EOCRC. This will be crucial in developing comprehensive preventive strategies to address the increasing incidence of this malignancy in younger populations.

Research has shown that racial/ethnic disparities exist in outcomes for colorectal cancer (CRC) patients, but there are no studies assessing inpatient palliative care utilization and hospitalization outcomes in this population. We examined racial/ethnic disparities in palliative care utilization and hospitalization outcomes among CRC and early-onset CRC patients.

Using National Inpatient Sample (NIS) data collected between 2016 and 2018, cross-sectional analyses were performed. Descriptive analyses were done, stratified by race/ethnicity. Multivariable logistic and linear regression models were used to examine racial/ethnic differences in palliative care utilization, inpatient mortality, chemotherapy/radiotherapy use, length of stay and total hospital charges among hospitalized patients with CRC and early-onset CRC.

Blacks had higher odds (AOR: 1.09; 95% CI: 1.03-1.16) of receiving palliative care consultation while Hispanics had lower odds (AOR: 0.90; 95% CI: 0.84-0.96) compared to Whites. Blacks had 1.1 times higher odds (95% CI: 1.01-1.18) of inpatient mortality relative to Whites while Hispanics had 16% (AOR: 0.84; 95% CI: 0.76-0.93) lower odds of inpatient mortality. Compared to Whites, Blacks (AOR: 1.99; 95% CI: 1.64-2.41), Hispanics (AOR: 2.49; 95% CI: 1.94-3.19) and colorectal cancer patients in the other category (AOR: 1.72; 95% CI: 1.35-2.18) were more likely to receive inpatient treatment with chemotherapy/radiotherapy. Furthermore, Black patients were 1.1 times (95% CI: 1.06-1.14) more likely to have a length of stay more than 5 days. Blacks (𝛃: $3,096.7; 95% CI: $1,207.0-$4,986.5) Hispanic (𝛃: $10,237.5; 95% CI: $7,558.2-$12,916.8) and other patients (𝛃: $6,332.0; 95% CI: $2,830.9-$9, 833.2) had higher hospital charges relative to their White counterparts. Among patients with early onset CRC, Blacks had higher palliative care use (AOR: 1.29; 95% CI: 1.10-1.51) and inpatient mortality (AOR: 1.38; 95% CI: 1.06-1.79) while Hispanics reported $5,589.7 (95% CI: $683.2-$10,496.2) higher total hospital charges and were more likely to receive inpatient chemotherapy/radiotherapy (AOR: 2.48; 95% CI: 1.70-3.63).

Further research is needed to explore specific cultural, socioeconomic, and political factors that explain these disparities and identify ways to narrow the gap. Meanwhile, the healthcare sector will need to assess what strategies might be helpful in addressing these disparities in outcomes in the context of other socioeconomic and cultural factors that may be affecting the patients.

The number of young patients with colorectal cancer (CRC) is increasing. However, sex-dependent differences in the prognosis of young CRC remain unknown.

We investigated patients aged <70 years with stage III CRC treated between January 2000 and December 2010 in 24 Japanese referral hospitals. Patients were divided into subgroups by age of 50 years (early-onset and late-onset groups) and sex, and clinical characteristics and survival outcomes were compared. Risk factors associated with poor survival outcomes were also analyzed.

Among 4758 consecutive patients, 771 (16%) were <50 years. Regardless of sex, there were more patients with rectal cancer and treated with adjuvant chemotherapy in the early-onset group. Among males, tumors in the early-onset group were poorly differentiated (p < 0.001), and patients were diagnosed at an advanced N stage (p = 0.010). Among females, there were more patients with left-sided cancer in the early-onset group (p < 0.001). Relapse-free survival (RFS) and overall survival (OS) were worse in the early-onset group than in the late-onset group (5-year RFS rates: 58% and 63%, p = 0.024; 5-year OS rates: 76% and 81%, p = 0.041, respectively), while there were no age-dependent differences in the survival outcomes of female CRC patients. A multivariate analysis identified age <50 years as one of the independent risk factors associated with poor RFS in male stage III CRC patients (p = 0.032) CONCLUSIONS: Young male patients with stage III CRC showed poorer survival outcomes than their older counterparts. Therefore, age- and sex-related differences in the incidence of CRC recurrence need to be considered.

The outstanding efficacy of immunotherapy in metastatic dMMR/MSI gastro-intestinal (GI) cancers has led to a rapid increase in the number of patients treated. However, 20-30% of patients experience primary resistance to immune checkpoint inhibitors (ICIPR) and need better characterization.

This AGEO real-world study retrospectively analyzed the efficacy and safety of ICIs and identified clinical variables associated with ICIPR in patients with metastatic dMMR/MSI GI cancers treated with immunotherapy between 2015 and 2022.

399 patients were included, 284 with colorectal cancer (CRC) and 115 with non-CRC, mostly treated by an anti-PD(L)1 (88.0%). PFS at 24 months was 55.8% (95CI [50.8-61.2]) and OS at 48 months was 59.1% (95CI [53.0-65.9]). ORR was 51.0%, and 25.1% of patients were ICIPR. There was no statistical difference in ORR, DCR, PFS, or OS between CRC and non-CRC groups. In multivariable analysis, ICIPR was associated with ECOG-PS ≥ 2 (OR = 3.36), liver metastases (OR = 2.19), peritoneal metastases (OR = 2.00), ≥1 previous line of treatment (OR = 1.83), and age≤50 years old (OR = 1.76).

These five clinical factors associated with primary resistance to ICIs should be considered by physicians to guide treatment choice in GI dMMR/MSI metastatic cancer patients.