Clinical Features in Patients With Early-Onset Colorectal Cancer

An Evaluation of Data From the StuDoQ Database

Background: The incidence of colorectal cancer (CRC) in patients who are less than 50 years old (early-onset colorectal cancer, EO-CRC) has risen markedly around the world in recent decades. Because of a lack of early detection programs for young patients, EO-CRC is often not detected until it has reached an advanced stage. In this study, we compared surgical patients with EO-CRC to those with so-called average-onset CRC (> 50 years; AO-CRC) using data from a large patient collective.

Methods: 63 565 cases of CRC from the years 2013–2022 were identified in the StuDoQ database of the German Society for General and Visceral Surgery (Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie, DGAV) and were analyzed on the basis of tumor-related and perioperative data for each of two groups, EO-CRC (3549 patients) and AO-CRC (60 016 patients).

Results: The mean age in the two groups was 42.50 ± 6.3 and 71.59 ± 10.3 years. In the EO-CRC group, 26.2% of the patients were under 40, and 50.4% were under 45. Men predominated in both groups. The distribution of tumor sites differed, with more rectal carcinoma and left-sided CRC in the EO-CRC group. More patients had nodal or distant metastases in the EO-CRC group. Compared to patients in the AO-CRC group, those in the EO-CRC group much more commonly had inflammatory bowel disease (OR 5.83, 95% confidence interval [4.73; 7.16]), a genetic predisposition (OR 4.36 [3.54;5.35]), or a positive family history (OR 4.54 [4.17; 4.95]).

Conclusion: This analysis reveals that patients with EO-CRC differ markedly from those with AO-CRC in tumor-related data, multimodal treatment approaches, and perioperative outcomes. Risk-based, individualized early detection programs should be established to prevent the progression of undetected EO-CRC.

Cite this as: Wirth U, Schardey J, Scholz F, Niedermaier T, Germer CT, Kroesen AJ, Pantelis D, Reissfelder C, Rentsch M, Ritz JP, Schäfer N, Andrassy J, Werner J, Kühn F: Clinical features in patients with early-onset colorectal cancer: An evaluation of data from the StuDoQ database. Dtsch Arztebl Int 2025; 122: 235–9. DOI: 10.3238/arztebl.m2025.0018

Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide (1, 2). The introduction of early detection programs has led to an overall decline in incidence (1, 2, 3, 4), despite the fact that CRC has been rising for many years in patients aged under 50 years (referred to as early-onset colorectal cancer, EO-CRC)(2, 5–7). By 2030, it is likely that colorectal cancer will be the commonest cause of cancer-related death in patients aged between 20 and 49 years (8). Therefore, the U.S. Multi-Society Task Force on Colorectal Cancer has reduced the recommended starting age for colorectal cancer screening to 45 years (3).

In Germany, EO-CRC accounts for approximately 5% of all CRC cases (1, 2, 5, 6). EO-CRC tends to be diagnosed at a more advanced cancer stage compared to the average-onset CRC (AO-CRC) that occurs later in life, thereby highlighting the need for improved early detection programs for an as yet unknown risk population (2, 6, 7, 9, 10). Clinical and molecular characterizations of EO-CRC are intended to improve our understanding of its carcinogenesis and the individual risk profiles (9, 10, 11, 12, 13, 14). Risk factors for EO-CRC that are already known include positive family history, genetic mutations, lifestyle factors, pre-existing diseases, and medication use (2, 7, 9, 13, 14, 15).

The literature already provides various epidemiological and prognostic data for EO- compared to AO-CRC (2, 9, 16). Patients with EO-CRC are often treated with curative intent as part of modern multimodal treatment approaches. Surgical strategy should not differ between EO-CRC and AO-CRC patients (17, 18, 19, 20, 21). Only scant information can be found in the literature regarding the surgical outcome of the perioperative reality of care for those affected by EO-CRC compared to AO-CRC (10).

The aim of this study was to compare demographic and outcome-related data of EO-CRC versus AO-CRC patients using a large surgical database and to analyze the quality of care of EO-CRC patients.

Methods

A total of 66 172 data sets were made available for analysis from the prospective registries StuDoQ|Kolonkarzinom (colon cancer) and StuDoQ|Rektumkarzinom (rectal cancer) of the German Society for General and Visceral Surgery (Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie, DGAV), of which 3147 cases were excluded due to missing, non-surgical, or inconclusive data. Demographic, tumor-related, and postoperative data were included in the analysis. Tumor stage was reported based on the TNM classification (22). Differences between the two groups in terms of perioperative data and oncologically relevant parameters were analyzed. To assess the effect of different variables on the risk of developing EO-CRC, multivariate binary logistic regression models were calculated, with odd ratios (OR) and corresponding confidence intervals (CI) reported. A more detailed description of the methodology can be found in the long version (eMethods Section).

Results

From the 227 participating hospitals, a total of 63 565 cases were analyzed, of which 3549 were EO-CRC and 60 016 AO-CRC. The share of cases per hospital was between 0.1 and 2.9% (median, 0.3%). In the EO-CRC group, 26.2% were aged under 40 years and 50.4% under 45 years (eFigure 2a, 2b). Demographic and tumor-related data are provided in the eTable. There were differences between the EO-CRC and AO-CRC groups in terms of gender distribution, BMI, ASA score, and all listed comorbidities (eTable). There were more cases of rectal carcinoma and left-sided CRC in the EO-CRC group (eFigure 2c). In EO-CRC surgical specimens, more lymph nodes were analyzed and more lymph nodes showed tumor infiltration. EO-CRC patients had higher UICC stages (III and IV) compared to those with AO-CRC. A family history of CRC was more common in EO-CRC. MSI status was analyzed more frequently in EO-CRC; the results of MSI analysis are not available in the database. Patients with EO-CRC were more likely to receive a recommendation for genetic counseling, and genetic counseling was actually provided in 31.1%, compared to 3.6% of cases in the AO-CRC group (eTable). The percentage of individuals with “inflammatory bowel disease” and “genetic predisposition” as risk factors was higher in the EO-CRC group compared to the AO-CRC group. EO-CRC patients were more likely to receive psycho-oncology counseling.

eFigure 1

eFigure 2

eTable

ASA, American Society of Anesthesiology Score

Surgical data and perioperative complications are summarized in Table 1. In the EO-CRC group, the percentage of minimally invasive (62.6 versus 49.7%) and robotic (6.0 versus 4.0 %) interventions was higher. Surgical time was longer in the EO-CRC group. CME or TME was more frequently performed in EO-CRC. Despite the higher percentage of rectal cancer cases, Hartmann’s procedure was less commonly performed in the the EO-CRC group. More patients received a protective stoma as part of tumor resection in the EO-CRC group. In the AO-CRC group, more emergency surgeries were performed. The rate of R0 resections was similar in the two groups.

Overall, wound infection and bleeding complication rates differed. For rectal cancer surgery, there was no difference in sacral wound-healing disorders, but more postoperative bladder emptying disorders. Non-surgical complications were more common in the AO-CRC compared to the EO-CRC group (Table 1). Perioperative mortality was significantly lower in the EO-CRC group compared to the AO-CRC group, with 0.1% of patients in the EO-CRC group dying due to the underlying disease and 0.3% due to perioperative complications, compared with 0.6% and 1.2%, respectively, in the AO-CRC group. Taking into consideration abdominoperineal resections and Hartmann’s procedures, the overall rate of anastomotic leak in EO-CRC was 8.1% compared to 7.7% in AO-CRC. The rates of surgery for rectal cancer in EO-CRC and AO-CRC were 11.1% and 11,5 %, respectively, and for colon cancer, 5.8% and 6.1%, respectively. Pre- and postoperative hospital stays were longer in the AO-CRC group.

Table 1

Tumor- and surgery-related data

The results of the logistic regression models to identify risk factors for EO-CRC are summarized in Table 2. A significantly increased risk was seen in the presence of inflammatory bowel disease (IBD; OR 5.83 [4.73; 7.16]), genetic predisposition (OR 4.36 [3.54; 5.35]), or positive family history (OR 4.54 [4.17; 4.95]). The associations between IBD or genetic predisposition and EO-CRC were markedly more pronounced in patients without a positive family history (OR 6.46 [5.12; 8.09] and OR 5.44 [3.83; 7.55], respectively). Smoking and immunosuppressive therapy were not found to be associated with EO-CRC. Alcohol abuse (OR 0.57 [0.44; 0.72]) and unintentional weight loss (OR 0.83 [0.73; 0.93]) were both inversely associated with the occurrence of EO-CRC.

Table 2

Odds ratios for early-onset CRC compared to average-onset CRC

Discussion

This data analysis based on Germany’s largest surgical registry (StuDoQ) reflects the perioperative reality of care and surgical outcomes of patients with EO-CRC compared to those with AO-CRC. The percentage of EO-CRC here was 5.6%. Epidemiological data from Germany put the share of EO-CRC relative to all CRC cases at 5.1% (6), while in the USA, this share is estimated to be around 10% of new cases (2). In our cohort, the relative proportion of female EO-CRC patients was higher than in AO-CRC cases, while the absolute proportion of males was higher in both cohorts.

The higher proportion of left-sided colon and colorectal cancer in patients with EO-CRC compared to AO-CRC has also been reported in other studies (2, 7, 10, 23).

The proportion of minimally invasive procedures in the EO-CRC group was higher, and overall, Hartmann’s procedure was less frequently performed despite advanced cancer stages. A possible explanation for this, based on our data, is the lower rate of comorbidities and low ASA scores among EO-CRC patients. With the exception of wound infection and bleeding complication rates, there was no difference in surgical complications between the two groups. The rate of anastomotic leaks was similar at approximately 6% for colon resections and 11% for rectal resections, comparable to the rates given in the annual reports of German colorectal cancer centers and German studies (24, 25, 26). The rate of perioperative complications was higher in the AO-CRC cases, as was mortality. Postoperative hospital stays were approximately 2 days longer for AO-CRC patients compared to EO-CRC patients.

Patients with EO-CRC were more likely to have advanced-stage cancer (III or IV), similar to international data, suggesting delayed diagnosis; in contrast to AO-CRC, EO-CRC is usually diagnosed only once symptoms have appeared, due to a lack of early detection programs and uncertainty regarding the risk group. The question of whether EO-CRC actually has more aggressive tumor biology has not been sufficiently investigated to date (2, 7, 9, 10, 13, 14, 23).

Our analysis shows that more radical resection of the lymphatic drainage area in the form of CME (complete mesocolic excision) or TME (total mesorectal excision) is performed more frequently in EO-CRC; this can improve prognosis, at least in node-positive patients (21). In addition, younger patients with advanced stages of cancer often receive more aggressive systemic and multimodal treatment regimens (2, 7, 10, 23). These differences in treatment strategy, which are likely due in part to the presence of fewer comorbidities and greater resilience in patients with EO-CRC, are consistent with available data (2, 6, 9, 17, 23). Despite the frequently more advanced tumors, EO-CRC has a similar prognosis overall to AO-CRC (10, 23).

As part of perioperative care according to defined DKG standards at German colorectal cancer centers, EO-CRC patients more frequently received psycho-oncological counseling, and the questionnaire on family history was completed more often. As expected, family history was positive in more cases, as described in other studies (2, 7, 13, 14). In line with the recommendations, younger patients were significantly more frequently advised to seek genetic counseling and indeed sought this counseling. Although patients with EO-CRC were more often investigated for microsatellite instability (MSI), the rates of MSI analysis and genetic counseling in the case of familial predisposition remain too low. Only through collaborative interdisciplinary efforts and specialized care for these patients in certified centers can these important aspects be comprehensively factored in alongside the primary cancer treatment, given that these aspects need to be implemented in a structured manner in certified colorectal cancer centers (27, 28). In view of the highly effective treatment options, all colorectal cancer patients should undergo MSI analysis in the preoperative setting. Recent data from German colorectal cancer centers demonstrate that this structured improvement in quality of care also has a positive impact on overall survival (29, 30).

Our data confirm the already established risk factors, which include a positive family history, a known genetic predisposition, and the presence of inflammatory bowel disease (2, 7, 13, 14). Other studies report obesity as a risk factor for EO-CRC (7, 13, 14). In our data, a higher BMI and alcohol abuse were associated with a lower chance (OR < 1) for developing EO-CRC compared to patients with AO-CRC. A comparison of AO-CRC and EO-CRC in our analysis showed that these two factors play a relatively smaller role as risk factors for EO-CRC than for AO-CRC, presumably due to younger patients’ shorter duration of exposure.

In view of the rising incidence of EO-CRC, the early detection strategy for colorectal cancer needs to be reassessed. A recent German study showed that although more than 80% of the population is motivated to participate in screening, less than half of those eligible actually do so (31). The low participation rate among individuals with a positive family history is particularly alarming (31, 32). In the USA, the starting age for colorectal cancer screening has already been reduced to 45 years (3). In our EO-CRC group, around 25% of patients were aged under 40 years and approximately 50% under 45 years, meaning that many of those affected would not benefit from a general reduction in the screening age to 45 years. Health economic studies have also been conducted for Germany, demonstrating a relevant gain in quality-adjusted life years at a moderate increase in costs (33). Consistent utilization of early detection programs in this known risk population could certainly have prevented some cases of EO-CRC or at least diagnosed them early enough for curative treatment (4, 9, 32). Timely surgical treatment—including prophylactic surgery—at low perioperative risk is established practice in less than half of patients with EO-CRC and a predictable risk (Lynch syndrome, familial adenomatous polyposis, or long-term ulcerative colitis) (7).

Modern iFOBT tests as well as further developments in non-invasive colorectal cancer screening now provide reliable methods that are also accepted by younger patients with a low inhibition threshold (9, 32, 34, 35). However, the at-risk collective remains largely unknown, with the known risk factors being of limited significance (7, 13, 14).

Increased awareness of EO-CRC is needed across the board, and patients with relevant clinical symptoms must be referred for appropriate diagnostic evaluation. Risk factors and molecular signatures need to be further elucidated in order to better identify the populations at risk. This would not only increase the quality of colorectal cancer early detection programs but also enable health economic benefits through the targeted selection of risk groups. In the case of known increased familial risk, there is currently at least the option of a timely screening examination, albeit unfortunately too rarely utilized (7, 32).

A limitation of our study is that it uses registry data of a surgical patient population in which metastatic cases with no surgical treatment options are underrepresented. Although a follow-up survey is planned in the StuDoQ registry, insufficient data were available for the data analysis. Other data of growing relevance, such as MSI status or histological subtyping, are not yet recorded in the registry. The cohort comprises only patients with colorectal cancer, no healthy subjects. Therefore, the odds ratios from the logistic regressions should not be interpreted as risk factors for EO-CRC compared to a healthy, age-matched normal population, but instead quantify, for the specified factors, the difference in risk for earlier onset (EO-CRC) of colorectal cancer compared to the population of patients with AO-CRC. Since the reported data represent information that is subject to mandatory documentation in the StuDoQ registry, they are virtually complete. Merely the data on nicotine consumption have been only partially recorded (approximately 80%). Incomplete datasets may introduce bias as a result of generalizations made during analysis.

Conclusion

This analysis reveals that patients with EO-CRC differ markedly from those with AO-CRC in terms of tumor-related data (tumor presentation, localization, and stage), the use of multimodal treatment approaches, and perioperative outcomes. These case of EO-CRC can only be addressed through risk-based, individualized early detection programs. Reducing the starting age for colorectal cancer screening, as in the the USA, would be a first step (3, 33). The focus of early detection programs is likely to shift to the introduction of non-invasive tests that have already been evaluated in large studies and are expected to be more widely accepted, but which currently still incur high costs (34, 35).

Conflict of interest statement
JPR is a board member of the German Society for General and Visceral Surgery (Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie).

JW is on the executive board of the German Society of Surgery (Deutsche Gesellschaft für Chirurgie, DGCH).

The remaining authors declare that no conflict of interest exists.

Manuscript received on 6 September 2024, revised version accepted on 28 January 2025.

Translated from the original German by Christine Rye.

Corresponding authors
PD Dr. med. Ulrich Wirth

Prof. Dr. med. Florian Kühn

eBox

Collaborators

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