1. Introduction and Background
CRC is the third most frequently diagnosed cancer type in the USA . Risk factors of CRC include older age, obesity, alcohol use, tobacco use, family history of CRC, hereditary genetic mutations, and presence of inflammatory bowel disease (the duration, extent, age at onset, and the relation of primary sclerosing cholangitis of the IBD further affect CRC risk) . CRC arises from the formation of polyps, unusually large growths in the colon or rectum. It is possible for polyps to progress to tumors, and expression profiles of proteins like cytokeratins and mucins can help determine prognosis and targeted therapy for specific types of colonic cancer . There are many different types of screening tests that can detect these colonic polyps. These screening tests are important preventive measures for early CRC detection. Early detection of CRC (by way of screening tests) is of vital importance in preventing CRC and catching it before it progresses to a more severe stage. In fact, because regular screening has increased so much within the past 20–30 years, the death rate of CRC has been decreasing . Similarly, dietary and chemopreventive measures also play a role in decreasing the overall incidence of CRC .
At the beginning of the COVID-19 pandemic, there was a complete halt in CRC screenings due to efforts to minimize person-to-person contact and to conserve hospital and medical resources for those exposed to COVID-19 . Unfortunately, the postponement of these screening tests for patients has had and will continue to have dire consequences, including more cases of CRC—potentially more severe ones—and additional CRC deaths that would have been prevented otherwise. With delayed or altogether missed screenings comes the potential for missed opportunities to detect polyps, diagnose CRC, and get more treatment for patients diagnosed.
Siegel et al. documented long-term trends in CRC incidence from 1975–2010 and mortality rate from 1930–2010 in the USA. They concluded that CRC was the most common cause of cancer death in the USA in the late 1940s and early 1950s and after that, the mortality rate began to fall in the early 1950s . In another publication, Siegel et al. presented that the age-specific risk of a CRC diagnosis fell for consecutive generations in the first half of the twentieth century but increased back to the level of those born in the late 1800s for current birth cohorts . By reviewing this literature, it is difficult to make any connection to the after-effects of the 1918 flu pandemic on the incidence or mortality of CRC. What impact COVID-19 will have on the incidence and mortality of CRC is ultimately unclear, but we can predict from the suggestive tell-tale signs along with prediction models and population data.
2. Resuming CRC Screening during COVID-19 and Beyond
Given the massive delays in screening with traditional methods, some healthcare centers looked toward allowing more CRC screenings to take place after initial waves of COVID-19. One study involving four healthcare locations in the UK was conducted to determine the safety of performing CTCs during the downturn period (May to July 2020) after the UK’s initial peak period of COVID-19. Computed Tomography Colonography (CTC) is a faster procedure compared to colonoscopy and lends itself to social distancing, given that the process involves a computed tomography (CT) scan where no patient-staff physical contact is necessary. The study was done safely as no patients or staff involved in the CTCs were found to have COVID-19 after the test 
. Additionally, Colon Capsule Endoscopy (CCE) involves minimal physical contact between patients and staff; in fact, only one medical provider is needed to administer the test to a patient that can also be done remotely 
. Note that throughout the pandemic, the use of telemedicine picked up to meet the needs of the healthcare system. This approach extends to CRC screening, where telehealth appointments regarding CRC screening have increased 
. Telehealth visits are still ongoing, even as in-person CRC screenings in hospitals or other medical settings are starting to resume 
. These appointments provide a platform for doctors to discuss available screening options with patients during these circumstances.
More importantly, the use of FIT is arguably the best alternative to, or prior to, colonoscopy procedure during the COVID-19 pandemic. FIT detects hidden blood in the stool, an early sign or warning of a silent cancerous lesion in the colon and/or rectum. To have maximum effectiveness, FIT must be done once a year. With the use of kits containing directions and materials, patients can simply do the test at home and then send it to their medical provider 
. FIT can serve as a triage to colonoscopy or other screening tests. One study in the UK found that using FIT during the pandemic allowed for improved utilization of resources regarding colonoscopy; specifically, by using the FIT before colonoscopy, they found that the number of patients referred for a colonoscopy decreased by 28% while still maintaining the amount of CRC diagnosis 
. This trend was found when they looked at the number of colonoscopies performed over the course of 26 March 2020 to 2 July 2020 compared to 1 October 2019 to 31 December 2019, where there was no statistically significant difference in the number of CRC diagnoses. By not having colonoscopies (when they are not strictly necessary), it saves time and money for providers and patients who would have had to undergo colonoscopy if they had not first received FIT 
. To give some context, in the UK, it costs the National Health Service (NHS) approximately £372 for a colonoscopy, as compared to £5 for each FIT 
. While in the U.S., a colonoscopy costs an average of $2750 for a patient and depending on the type of insurance they have, they could be paying varying amounts; or, with no insurance, patients would have to pay the full amount 
. In 2017, NHS funded a study known as NICE FIT study. It was conducted in 50 hospitals in UK with 9822 subjects to assess effectiveness and the accuracy of the home-based stool testing kits (FIT) to reduce invasive screening procedures like colonoscopies and results have recently been published 
. According to the results, the sensitivity of FIT for CRC in high-risk patients was 97.7% and 92.2% at cut-off values of 2 and 10 μg hemoglobin per g of stool sample. Similarly, it showed 94.3% and 86.6% sensitivity in low-risk patients at the same cut-off. These results confirm the effectiveness of FIT use in investigations for CRC screening.
Similarly, Issaka et al. used a developed simulation model to determine that during a period of fewer CRC screenings—i.e., the COVID-19 pandemic—an increase in FIT tests is associated with increased colorectal screenings and diagnoses. More specifically, they estimated that there would be an increase of about 2836 CRC diagnoses and 588,844 CRC screenings, totaling up to about 68.9% of CRC diagnoses being in the early stage of cancer 
. If this period of delayed CRC was extended, it was estimated that the number of screenings and diagnoses would also go up 
. Thus, while a FIT test does not provide all the benefits of a colonoscopy, it is a crucial tool in distanced CRC screening to close the gap during the COVID-19 pandemic. Not only is this type of test beneficial for maintaining the presence of screening, but it can also help to reduce racial and socioeconomic disparities in that it provides an at-home, lower-cost alternative to the traditional colonoscopy 
. Although racial disparity is not the main focus of this review, it should be noted that this existing issue of disparity in cancer prevention in minority and ethnic populations, was clearly exposed during the COVID-19 pandemic. Carethers et al. have discussed the beneficial role of at-home tests during the pandemic in decreasing overall disparity in medically underserved populations 
. These stool-based non-invasive tests should be further considered and implemented as part of regular CRC screening programs to prevent countless deaths. Beyond their immediate CRC benefit, they lead to changes done in the realm of public health and overall patient well-being.
While FIT can and likely should be used more given the COVID-19 pandemic to triage patients, it cannot replace colonoscopy procedure and its functional utility. Furthermore, challenges people face in receiving CRC screening pre-pandemic have been amplified even more during the pandemic. For instance, people who might have a harder time making themselves available to come get a colonoscopy, due to work obligations, for instance, are even more likely to not get a colonoscopy during the pandemic due to fear of contracting COVID-19. For example, one study found that nearly 20% of people in their CRC sample said that they would not be as likely to go do a screening test during the pandemic as compared to before the pandemic 
. Also, the fact that stress levels in the general population have increased because of the pandemic could be another reason why people are less likely to come to a hospital/medical center for any kind of CRC screening 
. Even beyond CRC, patients were still reluctant for any kind of healthcare appointment in general. In the same study, it was shown that a significant portion of the population, about 36.9%, have been reported to miss at least one healthcare appointment during the pandemic 
. Therefore, there is even more uncertainty around the impact of these missed appointments even beyond CRC. This can be seen with overall delayed diagnosis and missed diagnosis in other types of cancers as well, which again have an increased death rate associated with prolonged, late diagnosis of the disease.
As stated, and implied previously, there is no published literature detailing the effects of the 1918 flu pandemic on colorectal cancer incidence in the years following the 1918 flu pandemic. One reason could be lack of advanced medical care and unavailability of screening methodology almost a century ago. Of course, somewhat of a parallel between the 1918 flu pandemic and COVID-19 is that people were afraid to interact with others (outside of their homes), including physicians, for fear of contracting disease at the beginning and peak of the pandemic. The fact that present-day medical technology itself collapsed during the initial stages of the COVID-19 pandemic (meaning it could not be best-utilized given the limitations of the pandemic–social distancing, lockdowns, etc.) made it difficult to conduct routine screenings to obtain early cancer diagnoses.
Table 1 below summarizes the main findings of the studies related to COVID-19 included in this review.
Table 1. Summary of Main Findings of Studies Relevant to Colorectal Cancer Screening and COVID-19 Pandemic.
|Authors & Reference#
|Johnson BA et al. 
||Am J Surg
||A delay in surgeries for breast, lung, and colon cancer during the COVID-19 pandemic could decrease the chance of survival for patients.
|Lantinga MA et al. 
||Data from a database, encompassing 15 hospitals in the Netherlands were analyzed. Comparing the 15 March 2019–25 June 2019 period to the 15 March 2020–25 June 2020 period, it was seen that gastroscopies decreased by 57% and colonoscopies decreased by 55%.
|Wassie MM et al. 
||A retrospective data analysis was performed to compare colonoscopy data from April–June 2019 to April–June 2020 in South Australia. Colonoscopies decreased by 51.1% in the COVID-19 time period, and 46.1% of colonoscopies were delayed by at least 6 months.
|London JW et al. 
||JCO Clin Cancer Inform
||Data from the TriNetX data network, encompassing 20 medical centers and more than 28 million patients total, were analyzed. Comparing March 2019 to March 2020, there was a 38.4% decrease in CRC screenings. Comparing April 2019 to April 2020, there was an 84.5% decrease.
|Domper Arnal MJ 
||Presented at: UEG Week; 3–5 October 2021 (virtual meeting)
||An unpublished study of hospitals in Spain found there was a 40.4% decrease in CRC diagnoses in March 2020–February 2021, as compared to March 2019–March 2020.
|Maringe C et al. 
||This UK population-based modelling study aimed to estimate the effects of COVID-19-related delays of CRC screening. Data for 24,975 people with CRC was collected, and the estimation of additional death toll was 1445 to 1563 people up to five years post-diagnosis.
|Yong JH et al. 
||J Med Screen
||This study utilized microsimulation models for two types of cancers, including CRC, to determine what effects COVID-19 could have on CRC in Canada. With a 6-month delay in regular screening, CRC incidence and death would increase by 2200 people and 960 people, respectively.
|Kregting LM et al. 
||Br J Cancer
||Microsimulation models were used to simulate screening restart strategies for different types of cancers. If delays (due to the pandemic) were not caught up with, the CRC death rate would increase by 2.5 per 100,000 people in the next 10 years.
|Issaka RB et al. 
||JAMA Netw Open
||A simulation model was used to predict CRC outcomes between 2020 and 2023 in the U.S., including delays associated with the COVID-19 pandemic. The model showed that there would be 1,176,942 to 2,014,164 fewer CRC screenings and 8346 to 12,894 fewer CRC diagnoses. Also, an increase in FIT could cause increases in CRC screenings (655,825) and diagnoses (2715).
|Peprah D et al. 
||Br J Radiol
||Evaluation of CTCs conducted from May to July 2020 at four English hospital trusts was performed. 224 patients were scanned; of these, 169 who were followed up with on the phone reported no COVID-19 symptoms within 14 days of the test.
|MacLeod C et al. 
||Colon capsule endoscopy is a screening method that can be carried out safely during the COVID-19 pandemic and can be used to triage for colonoscopy.
|Wahezi SE et al. 
||Best Pract Res Clin Anaesthesiol
||Telemedicine has greatly increased due to the COVID-19 pandemic and will continue to be practiced post-pandemic. More research on telemedicine is needed to better compare it to in-person visits.
|Kadakuntla A et al. 
||World J Gastrointest Oncol
||The delays in CRC screening during COVID-19 can be overcome by doing more stool-based tests, adjusting screening protocols, and implementing more telehealth. Telehealth has advantages including convenience and improving patient compliance.
|Maclean W et al. 
||An observational cohort study in the UK was conducted to evaluate how FIT could affect utilization of resources and triage to colonoscopy. They found using FIT decreased further progression to colonoscopy from 62% (pre-pandemic) to 34%, while no significant change in the diagnosis rate.
|D’Souza N et al. 
||Br J Surg
||From October 2017 to December 2019, a study of 50 hospitals in England including 9822 subjects showed that the sensitivity of fecal immunochemical tests for CRC was 97.7% and 92.2% at cut-off values of 2 and 10 μg hemoglobin per g of stool sample.
|Carethers JM et al. 
||Cancer Prev Res (Phila)
||Minority populations in the United States face additional challenges in receiving CRC screening (e.g., finances, transportation, etc.). Thus, the delays in CRC screening during the pandemic will increase their CRC risk.
|Wilson R et al. 
||A cross-sectional online survey was conducted in the UK of over 7543 adults between August and September 2020, and follow-up interviews were conducted for 30 people. About 20% of participants indicated they would be less likely to go to a CRC screening test during the pandemic.
|Mason MC et al. 
||A cross-sectional study, done from January–April 2021, was performed (totaling 103 participants). Over 30% participants missed a routine colonoscopy during the pandemic.
There is no denying that the effects of COVID-19 on cancer screening are extreme. With interruptions and delays in screening tests, CRC mortality rates have been predicted to increase. Although the outlook of CRC seems ominous, one can take away countless lessons from the COVID-19 pandemic in terms of screening, diagnosis, and overall prevention of CRC. One key component to consider for the future of CRC screening and diagnosis is more utilization of alternative approaches, such as FIT tests. This remote option gives patients a lot of flexibility with their screening, as they are able to take the test safely in the comfort of their own home. It can also potentially provide a better allocation of resources, in terms of the fact that it can help prioritize patients who need colonoscopy over others due to the relative severity of their disease stage. Along with that, the accessibility of FIT tests can improve racial health disparities. Even as regular screening practices start to pick back up again as COVID-19 vaccines are being administered in many developed countries, the pandemic has still altered the framework through which healthcare providers view CRC screening. A lot has been learned and there are many key takeaways. One of these takeaways is that while colonoscopy will always be the gold standard in terms of CRC screening, FIT tests and other screening methods have significant strengths and unique attributes that make them utilizable and optimal in different situations.