Colorectal Cancer and Precursor Lesion Prevalence in Adults Younger Than 50 Years Without Symptoms

This cohort study investigates the incidence of colorectal cancer and prevalence of adenomas and other precursor lesions among adults younger than 50 years in Austria.


Introduction
Colorectal cancer (CRC) incidence and mortality decreased in the US and many European countries over the last 30 years among adults aged 55 years and older, which could be an effect of higher adherence to CRC screening programs.At the same time, an increase in mortality and incidence rates among younger patients was noticed. 1 Given that the incidence of CRC increases around age 50 years within a mean-risk population, screening programs have focused on this population so far.The American Cancer Society recommends that the age for individuals at mean risk undergoing first-time screening colonoscopy should be lowered to 45 years. 2 With the purpose of detecting and removing precancerous lesions, such as adenomas, within the same investigation, colonoscopy is the criterion standard for CRC screening.While having a higher risk of progression to CRC, adenomas are divided into nonadvanced (tubular adenomas <10 mm) adenomas and advanced (Ն10 mm in size, high-grade dysplasia, or villous histology) adenomas (AAs), and transition rates from AA to CRC were reported to greatly increase with age but were similar between male and female patients. 3 addition to age, patient sex should also have an influence on the age at which a screening colonoscopy is recommended given that several studies have found that male sex is an independent factor associated with CRC. 4 In a study by Ferlitsch et al, 5 the incidence of CRC and precursors in males aged 45 to 49 years was comparable with that of females 10 years older.
Meester et al 6 showed that CRC among individuals aged 40 to 45 years was diagnosed at a more advanced stage compared with in 1990.This indicates a real increase of CRC incidence and not only a shift in age at diagnosis.Despite the evidence of an increase in CRC incidence among younger adults, 7,8 data about the prevalence of precursor lesions, such as adenomas, among younger individuals, especially those without symptoms, are still missing.
Therefore, the aim of our study was to assess the prevalence of adenomas and AAs among younger adults without symptoms within the Austrian CRC screening program.Furthermore, the incidence of CRC within younger adults was evaluated and trends since 1988 were analyzed using data from Statistic Austria.

Methods
This cohort study was approved by the local ethics committee of the Medical University of Vienna.All patients had to sign written informed consent giving permission for data submission.The study was conducted following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

Study Design
There were 305 229 screening colonoscopies analyzed within the Austrian quality assurance program for screening colonoscopies, which was established in 2007 by the Austrian Society of Gastroenterology and Hepatology together with the National Cancer Aid.Participating endoscopists are surgeons, specialists for internal medicine, or gastroenterologists who must provide proof of at least 200 colonoscopies and 50 polypectomies under supervision and 100 unsupervised performed colonoscopies and 10 polypectomies per year.Approximately 45% of endoscopists in Austria participate in this project.Participating centers and physicians collect colonoscopy reports and histopathological analyses, which are transferred electronically to our database using a web form.An annual random sample checkup is conducted to check correctness of submitted data.Additionally, photo documentation is necessary to assess if cecum was reached.Twice a year, participants receive benchmark reports to inform them about their quality measures, such as adenoma detection rate, cecal intubation rate, sedation rate, and further parameters, to get feedback on their performance.
Information regarding serrated lesions (sessile serrated lesions and traditional serrated adenomas) was added to the report form in 2012.In 236 of 463 endoscopists participating in the quality assurance program (51.0%), participating physicians were using high-definition endoscopes.[11] Data were provided from 305 229 screening colonoscopies between 2008 and 2018, mostly involving patients aged 50 years and older.However, younger individuals were allowed to undergo a screening colonoscopy within this program if they were asymptomatic and the reason for the examination was patient fear of cancer.Patients with a positive family history, inflammatory bowel disease (IBD), or cancer symptoms were excluded from this study.Information regarding CRC incidence in Austria was provided by Statistic Austria for 1988 until 2018.

Exclusion and Inclusion Criteria
Endoscopists with fewer than 30 screening colonoscopies (560 individuals) and examinations with poor bowel preparation (8499 examinations) were excluded from this study, resulting in 9059 exclusions.A total of 296 170 screening colonoscopies remained after exclusion for study analyses within the screening program.

Statistical Analysis
Patient characteristics were described using median and IQR and categorical variables by absolute and relative frequencies.We used the χ 2 test to evaluate differences between groups.We divided all patients into age groups by steps of 5 years and calculated the prevalence of adenomas and AAs and the number needed to screen (NNS) for each group.AAs were defined as adenomas 10 mm or greater in size, with high-grade dysplasia, or with villous histology.Prevalences over time for adenomas and AAs were analyzed from 2008 to 2018.Information regarding serrated lesions, including sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs) were added to the colonoscopy report in 2012.Prevalence of serrated lesions was analyzed between 2012 and 2018.
Austrian data on CRC incidence from 1988 to 2918 were provided by Statistics Austria.Piecewise linear regression models were fitted using the segmented R package version 1.2.The number of breakpoints was limited to 1.We used the average annual percentage change (AAPC) to analyze trends in the incidence of CRC and precursor lesions.Statistical significance was denoted as P Յ .05.
Analyses were conducted as 2-sided tests using R statistical software version 4.1.0(R Project for Statistical Computing).Data were analyzed from January 2012 to December 2018.

Results
A total of 296 170 patients underwent a screening colonoscopy within the Austrian quality assurance
In patients aged 50 years or older, 62 384 individuals overall (21.9%;NNS = 5) had adenomas, while   The prevalence of adenomas is given for males and females.3).

Discussion
This large cohort study of 296 170 screening colonoscopies among patients who were asymptomatic, including 11 103 patients (3.7%) younger than age 50 years, found an increased prevalence of adenomas among younger adults since 2008.However, this trend was seen in all age groups.Therefore, these findings may not necessarily reflect a general increase in the presence of adenomas within younger adults but rather an improvement in screening quality and adenoma detection rate in general, as well as better equipment, which may be associated with higher numbers of detected adenomas.A study by Ahn et al 12 found that the miss rate for adenomas larger than 10 mm was 5.8%, showing that high-risk lesions have a relatively small risk for not being detected during colonoscopy.In our study cohort, we additionally found that the prevalence of AAs and the incidence of CRC were increasing, which cannot be explained only by quality improvement of screening colonoscopy.However, the prevalence of AAs, which have a higher risk of progression to CRC, changed from 4.0% in 2008 to 5.2% in 2018 among patients younger than age 50 years, while it decreased from 7.3% to 6.8% in patients aged 50 years or older.
Despite the increase in adenomas, the incidence of CRC in Austria decreased from 1988 to 2018 in males and females aged 50 years and older.This is likely associated with trends of the opportunistic screening program in Austria.The incidence in males younger than age 50 years increased.The incidence per 100 000 individuals of CRC in females younger than age 50 years changed from 9.7 incidents in 1988 to 7.7 incidents in 2018.However, the AAPC within this group was −0.2%, which suggests that the incidence in this group decreased when every year of this period is statistically taken into account.
Looking at different age groups, an increase of CRC incidence was noticed within males aged 40 to 44 years, while the AAPC within males aged 45 to 49 years declined.Within females aged 40 to 44 years, we also found an increase in CRC incidence, although the AAPC of 0.1% was not statistically significant, while the incidence within females aged 45 to 49 years decreased, although the AAPC of −0.9% was not statistically significant.In Austria, the age to start with screening colonoscopy was 50 years during the period analyzed in this study.Nevertheless, an increase in CRC incidence in younger adults was greater within males aged 40 to 44 years.
However, in 10.5% of patients younger than age 50 years, adenomas were found.The NNS of 9 represents that 9 patients younger than age 50 years need to be screened to find 1 adenoma.The NNS in those aged 45 to 49 years was almost comparable with that of those aged 50 to 54 years in this study.
A study by Ferlitsch et al 5 showed that the prevalence and NNS of AA in women were comparable to those in women aged 10 years younger.Our study found that the prevalence was higher and the NNS lower within males aged 40 to 44 years (5.9%;NNS = 18) than that among males aged 45 to 49 years (5.0%;NNS = 20).Thus, the NNS within males aged 40 to 44 years was comparable to that in females aged 20 years older (aged 60-64), with a prevalence of 5.5% and an NNS of 18.
Some studies reported an increase of CRC in younger adults.In a study by Vuik et al, 13 CRC incidence increased within individuals aged 20 to 49 years, especially those aged 20 to 39 years.
However, the reason for undergoing screening colonoscopy within those patients is unknown, and the trend of increasing incidence may be due to a selection bias.Furthermore, no increase in mortality was found.A study by Sehgal et al 14 showed that a colonoscopy was associated with a decrease in the risk of CRC by 50% when given at ages 45 to 49 years and of 68% when given at ages 50 to 54 years.However, most study patients were referred to colonoscopy due to symptoms, so outcomes associated with lowering the age to start screening colonoscopy within this age group remain unclear.
To our knowledge, our study is the first to evaluate trends in the incidence of CRC and precursor lesions within a large cohort of younger adults without symptoms, with a total of 11 103 screening colonoscopies in patients younger than age 50 years.Patients with IBD, cancer or CRC symptoms, or a positive family history of CRC were excluded from the study.The main reason for screening within those patients was patient fear of cancer.Additionally, the reason for the increasing prevalence of precursor lesions among younger adults is still unknown.Lack of physical activity, obesity, and other lifestyle factors are associated with an increased risk of CRC and adenomas. 15However, a limitation of our study was that we did not have data regarding lifestyle factors or comorbidities.
Moreover, our data also showed an increased incidence of serrated lesions, including SSLs and TSAs, from 2012 to 2018 in individuals aged younger than 50 years and 50 years or older.However, serrated legions were found in a total of 165 patients younger than age 50 years, not allowing for conclusions regarding the AAPC in this group.Starting in 2012, we have included sessile and traditionally serrated lesions in our report forms.Through our regular benchmark distributions and educational sessions, there has been an increasing emphasis on serrated lesions, which may account for the observed increase over the years.
The prevalence for adenomas in males aged 40 to 44 years in this study was 14.0%, suggesting that a screening colonoscopy finds an adenoma in every seventh male patient.Individuals aged 45 to 49 years already have access to screening colonoscopy in many countries.However, the NNS of 6 within males in this group is almost comparable with that of males aged 40 to 44 years, but those individuals do not have easy access to screening.The prevalence of AAs in males was higher within those aged 40 to 44 years than those aged 45 to 49 years, which raises the question of whether we should start at age 40 years, especially in males.Our data show that incidence within males increased more than that in females and the sex-specific gap is now even higher.These findings suggest that not only age but also sex should be considered for further recommendations.Our findings suggest that screening at age 40 years for males and age 50 years for females warrants thoughtful consideration.
Despite increasing incidence of adenomas and AAs among younger adults, the incidence of CRC increased only slightly among younger adults in general, which was mostly due to increasing incidence within males.In a 2022 study by Bretthauer et al, 16 screening colonoscopy reduced the risk of CRC, but there was no effect on CRC mortality.One reason could be that it takes more time to see the effects of screening on CRC mortality.However, that study included only patients older than age 50 years, and studies evaluating the effect of screening colonoscopy on CRC incidence and mortality in younger adults are still lacking.
Given that a screening colonoscopy is a procedure that depends on operator performance, quality improvement of screening should continue.Organized screening programs should be established in all countries with the aim of offering high-quality screening endoscopy and preventing progression to colorectal cancer.

Figure 2 .
Figure 2. Prevalence of Adenomas by Sex

Table 2 .
Prevalence of Adenomas and AAs