Colorectal cancer screening and prevention—pros and cons

Despite prophylactic lifestyle strategies and globally established screening programs, colorectal cancer (CRC) remains one of the most prevalent cancer entities especially in developed countries with 1.8 million new cases and 861,000 deaths in 2018 according to World Health Organization (WHO) Globocan Database.

Incidence of disease increases sharply with age, especially above age 50. However, more recent data show that previously low-risk populations below age of 50 exhibit an increase in incidence while a slow decrease in incidence above 50 years of age, presumably due to effective screening procedures, has been noted [1].

The development of the disease is known to progress over several years from precursor lesions, which are potentially curable, to fully developed CRC [2]. Therefore, detecting and treating these early lesions has become the objective of established screening programs worldwide resulting in a significant decrease in mortality [3‐5].

New chemotherapeutic regimes have mildly improved the survival of metastatic disease while raising the costs for health care providers immensely. Therefore, screening has not only decreased the mortality of CRC but might also be highly cost-effective [6].

The aim of this short review is to give an overview of the advantages and disadvantages of currently used screening procedures and tests.

Preventing CRC stands on two pillars: prophylaxis by eliminating risk factors and cultivating a healthy lifestyle and effective screening programs.

Drinking alcohol and smoking have been shown to increase CRC incidence and mortality [7, 8], and motivating the patient to eliminate those habits should therefore be a priority for healthcare providers. Furthermore, obesity and diet have been shown to have an impact on CRC incidence [9]. Reducing weight and red meat intake decreases the risk of developing CRC [10]; however, further recommendations on diet are less clear and partly conflicting. While some studies suggest a protective role of a diet rich in vegetables and fruits other studies have challenged this assumption [11, 12]. While more studies are required, it is recommended to closely follow the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines and recommendations [13]. The data is clearer for physical activity showing a reduction of CRC risk with regular physical activity in a meta-analysis of 21 studies [14].

Aspirin use has been shown to reduce the incidence of adenomatous polyps; however, due to its frequent side effects like gastrointestinal bleeding the intake as a prophylactic agent is not recommended [15].

Tumors shed different biomarkers including DNA, RNA, miRNA and proteins into the blood. Obtaining circulating tumor DNA may indicate relapse after surgical resection of CRC. However, liquid biopsy is limited when it comes to early detection of CRC or adenomas because of minimal amounts of ctDNA shed by early stages. Deviant methylation detection of free circulating DNA on the Septin 9 gene promoter is another approach used by the recently improved EpiproColon 2.0 assay, which demonstrated a sensitivity of up to 84% in a small cohort of stage I CRC. Similar markers have shown a comparable sensitivity and combining multiple biomarkers seems to improve the ability to detect CRC [30]. miRNA alterations which drive cells into an undifferentiated proliferative state have been shown to play a role in a variety of tumor entities including CRC. The most researched indicative marker is miR-21 with a pooled sensitivity and specificity of 72 and 85%, respectively. Combining multiple miRNA biomarkers on panel tests showed an improved sensitivity of about 81% and specificity of 84% [30].

Utilizing these techniques for screening is a promising new approach; however, currently no established markers used for screening are available and further prospective evaluation studies are needed for clinical use.

Recent epidemiologic data showing an increase in CRC incidence among young adults below 50 years of age and a concomitant decline in the screening cohorts aged 50 and above have raised the question whether to lower the starting age of screening programs to 45 instead of age 50 [31]. The American Cancer Society has already issued the recommendation to lower the starting age for all average-risk individuals to 45 [32]. Imperiale et al. highlight the potential benefit of this new approach, possibly detecting curable stage CRC in this age group, while also lowering the cost of cancer treatment. This has to be balanced by more unnecessary screening procedures and potential complications when lowering screening age even further alongside increased cost due to increased screening [31]. Therefore, it seems that screening colonoscopy from age 45 to 75 years every 10 years was most favorable [31]. However, the US Multi-Society Task Force on Colorectal Cancer, among others, still recommend to start screening at age 50 for individuals at average risk [24].

Some countries have started to use noninvasive stool tests with subsequent colonoscopy if the test turned out positive starting at age 45. Whether there should be a general recommendation for lowering the starting age for screening by colonoscopy for all average risk individuals requires further evidence.

It has been clearly demonstrated that screening for CRC and the removal of precancerous lesions by colonoscopy results in a reduction of incidence and mortality, while also being cost-effective for the healthcare system. Endoscopy is widely considered as a gold standard and is the only screening procedure that also allows to remove precancerous adenomas. However, studies comparing screening strategies that combine different available screening procedures at given intervals may yield comparative results with higher acceptance rates for noninvasive procedures. In a simulation study by the US preventive service task force, colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT and CTC every 5 years yielded comparable amounts of life years gained when performed in a screening population from 50 years of age 75 years of age [33]. A current comparative evaluation of FIT and colonoscopy for screening revealed a much higher participation rate in the FIT group and similar detection rates of CRC in both groups. More adenomas were however identified and treated in the colonoscopy group [22]. Potential complications of an invasive procedure such as colonoscopy, high cost and the reliance on high quality standards need to be taken into account. As no randomized controlled comparative studies are currently available screening procedures may vary by country also depending on resources within the healthcare system and patient acceptance. Noninvasive stool tests provide a good alternative for patients refusing colonoscopy or in countries with limited access to colonoscopy. Table 1 summarizes the currently internationally most established screening procedures and tests, and their level of recommendation based on the systematic review of evidence of the US Multi-Society Task Force on Colorectal Cancer [24]. Ultimately, the goal of screening programs should be to multiply participation rates and patient adherence. Newer developments such as liquid biopsy testing for biomarkers such as ctDNA and miRNA could further improve noninvasive CRC screening; however, further development and research is needed.

The positive impact of colorectal cancer (CRC) screening programs on CRC mortality have been well studied and a variety of different screening algorithms have been established worldwide. Still participation rates are fairly low and the potential benefit could be multiplied by increasing participation rates. Offering multiple screening tests may increase patient acceptance; however, due to the low sensitivity of noninvasive stool tests for precancerous lesions the only effective preventive procedure for CRC other than lifestyle modification remains colonoscopy.