Domain research was used and completed with other studies used in HAS report dated 2008 and information from HAS recommendation dated 2013. Systematic reviews referenced in HAS report 2008 {3, 8} were used as a basis for this result card. 

The screening methods gFOBT and FIT are non-invasive procedures that are therefore not likely to cause any direct harm.

Indirect harm can be caused by a wrong or delayed diagnosis (see Q6) or by harms related to subsequent colonoscopy. Indeed, participants with a positive result of the screening test are referred for further diagnostic evaluation by invasive procedures which may be associated with various adverse events (see point 1 Harms from colonoscopy).

Furthermore, gFOBT and FIT may have a psychological impact related to the procedure itself and related to positive results (see point 2 Psychological harms).

The overall number of adverse events may be influenced by the number of colonoscopies that depends on sensitivity and specificity of the screening test {3}.           1) Harms from Colonoscopy

Summary of results:

The overall colonoscopy related morbidity is estimated to 5%. Minor complications such as bloating, abdominal pain or other complications related to bowel preparation have been reported. Major complications are rare and include perforation of the gut and haemorrhage. Complications related to sedation (hypoxia) or cardiovascular complications can be also observed. Infection risks are very rare. {4, 1}

One study also addressed the embarrassment experienced during endoscopy {5}. 

The frequency of colonoscopy complications varies from one study to another and results from the different trials are presented further below for completeness of information.

As for the duration of harms Senore et al. {5} found that in about 90% of the cases symptoms were of short duration (arose within two hours from screening and were resolved within four hours).

Results from different trials:

•   [Cochrane systematic review:  Screening for colorectal cancer using the faecal occult blood test, Hemoccult; 2007, update 2011] {3}

A systemic review of literature published up to June 2010 has been done with a primary objective to determine whether screening for colorectal cancer using the faecal occult blood test (guaiac or immunochemical) reduces colorectal cancer mortality. Secondary objective was to evaluate the range of benefits and harms of screening.

Four randomised controlled trials (Nottingham, Funen, Goteborg, Minnesota) involving about 327,000 participants have been included in the review, all of them using Hemoccult test as screening method. In all of the trials, participants with a positive Hemoccult test were referred for further diagnostic evaluation, performed by colonoscopy in all trials except one (Goteborg), in which participants received sigmoidoscopy and double-contrast barium enema.

Among three trials that used colonoscopy as the primary means of further investigation, two reported adverse outcomes in detail (Minnesota, Nottingham) and found that the rate of perforation during colonoscopy is approximately 1 in 1,400.  

In the Minnesota trial, of the 12,246 colonoscopies performed at the University of Minnesota hospital there were four perforations of the colon (all requiring surgery) and 11 serious bleeding complications (3 requiring surgery). The Nottingham randomised trial reported that there were seven complications (out of 1,474 procedures) associated with colonoscopy (five perforations, one major bleed, one snare entrapment). Six of these complications required surgery although none of these patients died from the colonoscopy complications.

Although participants from the Goteborg trial mainly received sigmoidoscopy and double-contrast barium enema in further investigation, colonoscopy has been also done in case of repeated failure of other diagnostic methods or for polypectomy. Therefore, adverse outcomes for both flexible sigmoidoscopy and colonoscopy are reported in this trial. One patient's large bowel was perforated during diagnostic endoscopy. Four perforations of the large bowel occurred during endoscopic polypectomy, and one case of bleeding occurred 12 days after polypectomy. No complications occurred in connection with the 1,987 double-contrast barium enemas.

•    Quintero et al, 2012: Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening,] {6}

A randomized, controlled trial involving asymptomatic adults compared one-time colonoscopy with FIT every 2 years in a screening setting. Adults with positive result on FIT were further invited to undergo colonoscopy. The study design allowed for crossover between the two study groups. [3]

Major complications occurred in 24 subjects (0.5%)[4] in the colonoscopy group (12 subjects with bleeding, 10 subjects with hypotension or bradycardia, 1 subject with perforation, and 1 subject with low blood saturation) and in 10 subjects (0.1%)² in the FIT group in patients who had subsequent colonoscopy (8 subjects with bleeding and 2 subjects with hypotension or bradycardia.

•   Guittet, L., et al. (2007). "Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population." {7}

This trial compared the screening performances of the gFOBT and the immunochemical faecal occult blood test (I-FOBT or FIT) in an average risk population sample of 10 673 patients who completed the two tests.

Patients with at least one positive test result were asked to undergo colonoscopy. One perforation was recorded in 644 colonoscopies. (0.2%)

•   Senore, C., et al. (2011). "Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting." {5}

The study compared subjects’ experiences of sigmoidoscopy and colonoscopy in a screening setting. They especially focused on side-effects other than perforation and bleeding risk, and provided an active follow-up beyond the period spent in the endoscopy unit with a prospective 30-day follow-up after discharge.

Adverse effects associated with the preparation were reported by 15.0%[5] of the interviewees examined with sigmoidoscopy and by 30.1%³ of those examined with colonoscopy (OR: 2.44; 95% CI: 2.01–2.95). The most common complaints in both groups were abdominal pain, bowel distension and anal irritation, mentioned by 10.1%, 7.7% and 3.2% of people in the sigmoidoscopy group and by 12.8%, 11.1%, and 7.3% of those in the colonoscopy group.

People experiencing more than mild embarrassment were 3.8% and 4.0% for sigmoidoscopy and colonoscopy respectively.

Immediately after the test, some patients reported severe pain (16.6% in the colonoscopy group and 9,5% in the sigmoidoscopy group).

Adverse physical reactions following discharge were reported by 521 (34.7%) people examined with sigmoidoscopy and by 448 (37.4%) of those examined with colonoscopy. In about 90% of the cases symptoms arose within two hours from screening and resolved within four hours.

Bowel distension and abdominal pain were the most common complaints, they were reported as the only symptom by 15.6% and 4.5% of interviewees examined with sigmoidoscopy and by 14.7% and 6.0% of those undergoing colonoscopy screening, and in association by 8.5% of people examined with sigmoidoscopy and by 8.8% of those undergoing colonoscopy.

Patients who underwent sedated colonoscopy were more likely to report feeling dizziness after discharge (3.4%) than those having an unsedated exam (0.8%).

The 30- day admission rate was 1.34% (16/1197), 1.13% (11/976) and 0.88% (12/1363) in the sigmoidoscopy, colonoscopy and FIT arms respectively. In addition, four people (2 in the sigmoidoscopy and 2 in the colonoscopy arm) reported at the phone interview having been referred to an emergency department following onset of abdominal pain (3 cases) or hypotension: they recovered and were discharged within a few hours.

2) Psychological harms

Summary of results:

The screening procedures gFOBT or FIT, eventually followed by a colonoscopy, may have a psychological impact related to the procedure itself and related to positive results. Impact of screening on daily life and levels of anxiety after a positive result of the screening test have been reported in several studies. Outcomes of these studies were psychiatric morbidity, anxiety, distress, worry and the effect on daily life {8}.

One study in particular {9} reported quality of life and level of anxiety of participants of a colorectal cancer screening programme that have been tested by FIT or by sigmoidoscopy, concluding that  the burden of participating in a CRC screening programme is limited.

•   Results from different trials:[NHS Centre for Reviews and Dissemination : Diagnostic Accuracy and Cost-Effectiveness of Faecal Occult Blood Tests Used in Screening for Colorectal Cancer: A Systematic Review, 2007] {8}

Three studies have been cited in the NHS systematic review: Parker et al (2002), Mant (1990) et al and Lindholm et al (1997).

In the trial by Parker et al., there was no significant difference in the proportion of participants with psychiatric morbidity, before and three months after FOBT was offered. For people with a false positive FOBT, the highest anxiety levels occurred after notification of a positive test and before colonoscopy. The lowest level of anxiety was experienced the day after colonoscopy and this remained low one month later.

In Mant’s paper 68% of people who had a false positive FOBT and filled the questionnaire reported experiencing distress, (62% of these slight distress, 24% moderate distress, and 14% very distressed). Sixty nine percent reported being worried that they may have cancer, and of these 68% reported experiencing slight distress, 24% moderate distress, and 8% were very distressed. Forty three percent of people found the dietary restrictions slightly disruptive, 6% moderately disruptive and 4% very disruptive. Delays in the process caused slight worry for 26% of people, moderate worry for 6%, and 4% were very worried.

In Lindholm’s paper 46% of addressed people were worried by the invitation, and refused to participate, and of these, 15% were ‘extremely’ worried. Sixteen percent of those who participated in the screening reported being ‘extremely’ worried. For people with a negative FOBT, 19% experienced severe worry, and of these 18% said that their daily life was negatively affected. For people with an initial positive FOBT, 60% experienced severe worry, and 38% said there daily life was negatively affected.

•   Kapidzic, A., et al. (2012). "Quality of life in participants of a CRC screening program."{9}

Quality of life and level of anxiety have been studied in Dutch participants of a colorectal cancer screening programme that have been tested by FIT or by sigmoidoscopy. Participants from CRC screening trials were sent a questionnaire, which included validated measures on generic health-related QOL, generic anxiety and screen-specific anxiety. The main research question of the study was whether QOL differed in participants with a positive test result compared with participants with a negative test result.

Thisretrospective questionnaire survey showed slightly worse QOL scores among positive FIT participants compared with FIT negative participants. Screen-specific anxiety was significantly higher among both positive FIT and sigmoidoscopy participants, indicating that a positive test result has a negative impact on participants’ emotional well-being, although differences were small and not clinically relevant. A prospective study needs to be conducted, where participants receive questionnaires at different time points during the entire screening process.

  [1] 0,5% of the screened population [2] 0.1% of the screened population [3] Among subjects who were assigned to undergo colonoscopy, 5649 subjects accepted the proposed strategy, whereas 1706 requested to be screened by means of FIT. Of the 5649 subjects who agreed to undergo colonoscopy, 4953 actually did so. Among subjects who were assigned to undergo FIT, 9353 subjects accepted the proposed strategy (and a total of 8983 subjects really underwent FIT) , whereas 117 asked to be screened by colonoscopy (and 106 really completed the test). This cross-over resulted in a total of 10611 patients receiving FIT and 5059 completing colonoscopy in a screening setting. Additionnaly, 663 FIT positive patients received colonoscopy. [4] As-screened population [5] Percentage calculated with regards to the total number of patients that completed the 30 days follow-up

•   There is no direct harm caused by either gFOBT or FIT. Indirect harm can be caused by a wrong or delayed diagnosis or by harms related to subsequent colonoscopy. Eventually, psychological impact of the screening can be observed.

•   The total number of adverse events may be different between gFOBT and FIT according to the number of colonoscopies which is related to the specificity and sensitivity of the test.

•   Population of some analysed studies {6, 5} slightly differs in age from the target population defined by the EU recommendations as they do not cover the entire age range 50-74 years.

•   All studies differed with respect to their approach to calculating the % of complications.

•   In Kapidzic’s study {9} of Quality of life, some patients filled-in the questionnaire up to 5 years after the screening took place, which could have influenced the QoL results. They also indicate having used a Dutch version of PCQ questionnaire for screen-specific anxiety. 

This result card is removed, because it is not relevant.

This result card is removed, because it is not relevant.

This result card is removed, because it is not relevant.

This result card is removed, because it is not relevant.

Domain research was used and completed with information from HAS report dated 2008 {2} and recommendation dated 2013{1}. Systematic reviews referenced in HAS report {8} were used as a basis for this result card.

Summary of results:

The screening methods gFOBT and FIT are non-invasive procedures that are therefore not likely to cause any direct harm to the participants. Harms can be observed on a psychological basis or can be due to subsequent colonoscopy examination, with different timing.

Summary table of selected references

Results from different trials:1) Physical reactions to colonoscopy

Risks of severe complications such as gut perforation and hemorrhage can be immediate or delayed (7-21 days after colonoscopy). {1}

One study specifically examined the risk of immediate and late reactions other than gut perforation and hemorrhage after colonoscopy and sigmoidoscopy in a screening setting {5}.

Among immediate reactions, patients reported serious reactions following bowel preparation (mainly abdominal pain, bowel distension and anal irritation), severe pain immediately after the exam and embarrassment. {5}

The most common post-procedural complaints were abdominal distension and pain.

2) Psychological impact

Psychological impact can be observed as well during the whole period of testing, including time before testing and time after obtaining the results. In a clinical trial (Parker et al, 2002) a general health questionnaire was sent to 2184 subjects before the offer of screening, and 1541 (70.6%) were returned. Of the 1693 subjects offered the questionnaire 3 months after the offer of screening, 1303 (77%) returned it. Anxiety scores were measured in 100 test positive patients and were highest after notification of a positive test and before investigation by colonoscopy. In patients with false positive results, scores fell the day after colonoscopy and remained low 1 month later. No sustained anxiety has been seen in screening participants.

Harms can be observed on a psychological basis or can be due to subsequent colonoscopy examination, with different timing.

Domain research was used and completed with information from in HAS recommendation dated 2013 {1}. 

As the screening test is non-invasive procedure, no change in direct risk is expected over time. Risk of false negative results may be reduced by a better sensitivity of the test used for screening. Concerning false positive results, they may be reduced by better education and better compliance of the patient. As FIT is specific for human hemoglobine {1}, its use reduces the number of false positive results due to non-compliance of participants related to diet restriction.

Risk of complications of colonoscopy and sigmoidoscopy may be reduced by an experienced endoscopist. {1}

The reproducibility of the result and the consequent risk of false positive results may be influenced by patient’s non-compliance. However, no studies comparing the impact of patient’s compliance (diet, education) on the results of FIT and gFOBT are available.

Risk of complications of colonoscopy and sigmoidoscopy may be reduced by an experienced endoscopist. However, data on the reduction of the number of complications related to experience of endoscopist have not been found neither.

Domain literature search was used.

No susceptible patient goups are known, that would be more likely to be harmed through use of FIT or gFOBT. However there is one study addressing the risk of harm of colonoscopy in patients with co-morbidities.

• Hughes, K., B. Leggett, et al. (2005). "Guaic versus immunochemical tests: faecal occult blood test screening for colorectal cancer in a rural community." {13}

Complications related to colonoscopy are increased if participants with major co-morbidity are included in screening and referred for colonoscopy. One such patient of 92 patients, who underwent colonoscopy, developed heart failure during colonoscopy preparation.

No other susceptible patient groups were found from literature, that could be more likely to be harmed through use of FIT or gFOBT. One study suggests, that patients with co-morbidities can more likely to be harmed through use of colonoscopy.

The domain literature search and additional search was used.

False-positive test results may cause anxiety and stress to patients. Also there is the possibility of overdiagnosis (leading to unnecessary investigations or treatment) and the complications associated with treatment. However no studies were found to address the possibility of overdiagnosis. False-negative test results may delay the start of treatment. {8} 

False-positive and false-negative tests may cause anxiety, stress, overdiagnosis and delay in the start of treatment.

The domain literature search and additional search was used.

The risk of harmful events can be increased due to unexperienced laboratory personnel, who make mistakes, when reading test results{8}. There are many factors infuencing gFOBT test results – food, consumed medications, faecal hydration. FIT test, however does not have dietary or medications restrictions {13}.

• [NHS Centre for Reviews and Dissemination : Diagnostic Accuracy and Cost-Effectiveness of Faecal Occult Blood Tests Used in Screening for Colorectal Cancer: A Systematic Review, 2007] {8}

The accuracy of FOBTs depends upon appropriate performance and interpretation of the test(s). Interpretation of FOBTs may be problematic when they are done by inexperienced personnel. In a retrospective review of questionnaires applied to accredited laboratory personnel (in order to determine their ability to interpret FOBT results), 12% were unable to correctly interpret sample test cards (mainly false-positive results). This finding raised concerns that people with detectable colorectal cancers may be missed, solely because of errors in interpretation. One suggestion to improve test interpretation is the use of tests with automated reading. Alternatively a centralised location for the collection, processing, and interpretation of all tests would facilitate measures to improve consistency.

Guaiac tests are generally best at detecting large, more distal lesions. Because they depend upon peroxidase or pseudo-peroxidase activity in the faeces, and are not specific to the pseudoperoxidase activity of human haemoglobin, many variables are said to influence their results. These include dietary factors, for example animal haemoglobin/myoglobin in red meat, fruits and vegetables high in peroxidase activity (false-positive results), high doses of vitamin C (false-negative results), aspirin or other medication that may cause gastrointestinal bleeding (false-positive results) and faecal hydration. The drying out of the faecal specimen and exposure to high ambient temperature can also result in false negative findings. Conversely rehydration of the sample may deactivate the peroxidases from fruit and vegetables reducing the number of false positive results. A systematic review of five RCTs of CRC screening using a guaiac test (Haemoccult) suggested that dietary restriction during unrehydrated FOBT may not be necessary as it did not appear to affect positivity rates and completion rates. However, the review did not include evidence on the use of more recent guaiac tests such as Haemoccult Sensa, which are believed to be more susceptible to the effects of diet. It also failed to account for dietary differences between countries and ethnic groups

Complications from colonoscopy may depend on the education and experience of health professional {13}.

The risk of harmful events may be increased due to unexperienced laboratory personnel, dietary and medication restrictions (gFOBT) and education and experience of health professionals.

The additional literature search was used.

The alternative technologies used for the same purpose are – colonoscopy (not specifically addressed here as covered elsewhere in the document), flexible sigmoidoscopy, computer tomography (CT) and barium enema. As all of the three techniques are invasive, non-invasive FIT and gFOBT tests are safer in terms of colonic perforation, ionizing radiation or sedation performed.

Levin, et al. (2002). Complications of screening flexible sigmoidoscopy {16}

Flexible sigmoidoscopy (FS) is an invasive diagnostic test and can cause perforation in the lining of the bowel, bleeding and infection. Sedation can cause problems with breathing, heart rate and blood pressure. The principal finding of this study was that the rate of complications after FS is modest. Approximately 1 in 5000 screening subjects was hospitalized for a gastrointestinal complication, and 1 in 16,000 was hospitalized for a serious complication. Colonic perforations, serious bleeding, and diverticulitis leading to surgery each occurred in this population less often than in 1 of 50,000 examinations.

Broadstock, (2007). Computed tomographic (CT) colonography for the detection of colorectal cancer – a Technical Brief {17}

Computer tomography has following disadvantages: patients are exposed to ionizing radiation, although low-radiation dose protocols are under investigation. False positives can occur as a result of retained stool in the bowel, diverticular disease (which can produce poorly distensible areas of the colon), or thickened bowel folds. Patients are associated with a very small risk of colonic perforation in CT colonograpy. Both, computer tomography and barium enema, were said to expose patients to ionizing radiation and to be associated with a very small risk of colonic perforation.

The domain literature search was used.

Wong et al {15} evaluated the factors associated with choosing immunochemical faecal occult blood test (FIT) or colonoscopy for colorectal cancer (CRC) screening among 3430 Chinese participants taken from a community-based cancer screening programme in Hong Kong and determined that the choice of the colonoscopy test was significantly influenced by the perceived discomfort induced by screening (OR 1.36, 95% CI 1.15–1.59, P < 0.001) . The findings show that those who did not perceive that CRC screening would inflict physical discomfort preferred colonoscopy. The update of this preliminary study {14}which includes 7845 patients also finds that the perception of the cancer screening being uncomfortable or embarrassing were associated with lower odds of choosing colonoscopy over FIT (p<0,001). The perception of risk did not significantly affect the choice of the tests.

Hol et al {12}compared the perceived test burden and acceptability of guaiac-based faecal occult blood test (gFOBT), faecal immunochemical test (FIT) and flexible sigmoidoscopy in a representative sample of the Dutch population randomly invited for the two tests and showed that FIT was perceived as slightly less burdensome than gFOBT due to less reported discomfort during faecal collection and test performance. The vast majority of participants would encourage friends or relatives to undertake either gFOBT or FIT (gFOBT: 96%, 95.8%; p=0.76) and were willing to attend a successive screening round (gFOBT: 94.1%, 94%; p=0.76). A significantly smaller proportion of FS screenees were willing to attend another round (83.8%; p< 0,005). The perceived risk of colorectal screening did not significantly influence the recommendation to friends and/or relatives, or the willingness to return for a successive screening round.

The results of 4 focal groups (n=28) set up to explore the perceptions of colorectal cancer and fecal immunochemical testing among African Americans in a north Carolina Community {11} showed that negative attitudes about FIT were mostly due to embarrassment when returning samples. The multistep instructions were also acknowledged as a potential problem for uptake.

The comparison of the uptake of FIT and gFOBT in 5,464 and 10,668 randomized eligible participants in a screening programme in the Clalit Health Service (Israel) {10} showed that compliance in taking the kits was better (but not statistically significantly better) with gFOBT  (37.8% vs. 29.3%; OR 1.43 [95% CI 0.73–2.80]; P = 0.227). Independent factors associated with increased compliance were female gender, age ≥ 60 years and immigrant status.

The evidence is insufficient in quantity and quality to establish how the existence of perceived harms influences acceptability or tolerability. The findings suggest that the factor that influences acceptability is not so much risk perception but the discomfort of the test procedures {12, 14, 15}. The preference of FIT over colonoscopy can be influenced by the perceived discomfort and embarrassment associated with the latter but there seems to be many other factors involved, like age, educational level, occupational status or family history of colorectal cancer, that should be further explored {14}.

Even though the fewer number of faecal samples required for FIT with respect to gFOBT seems to lead to less discomfort during faecal collection, as the gFOBT has to be performed on three consecutive bowel movements and FIT is a one-sample test, evidence suggests that both tests are equally tolerable {12}. Both tests seem to be equally recommended to their family and/or friends by screening participants but it is not clear how this and other differences, like kit presentation, can influence the acceptance of both tests. Whilst some studies suggest that participation could be similar or even slightly higher with gFOBT {10}, others enhance that patients receiving immunochemical kits are approximately twice as likely to participate than those receiving the guaiac kit {13}. It would be reasonable to think that persons would prefer the user-friendly characteristics of the immunochemical test (more convenient, less messy, no dietary restrictions) but it must be acknowledged that these tests may be challenging to some people and thus acceptance could depend on the setting {11, 13}.

The domain literature search was used.

We found no studies that addressed occupational harms of FIT and gFOBT.

Universal precaution recommendations include the use of gowns to protect the skin and clothing from contamination with feces during procedures. Gloves should be worn during all procedures. Prolonged use of latex gloves may cause skin sensitivity, contact dermatitis or latex allergy. Both conjunctivitis and systemic infection can also occur from touching the eyes with contaminated fingers or others objects.

The domain literature search was used.

We found no studies meeting our inclusion criteria that addressed risks for public and environment of fecal immunochemical tests.

The domain literature search was used.

Only two organisational factors (dietary and medication restrictions, cooling measures) were considered to be potentially relevant, which could affect the harms. The accuracy of FOBTs depends upon appropriate performance and interpretation of the test and the interpretation of FOBTs may be problematic when they are done by inexperienced personnel (see SAF7).

In order to reduce the probability of a false positive result, dietary restrictions are usually recommended when guaiac-based tests are used. FIT tests have no dietary or medication restrictions {13}.

However, FIT test samples were requested in one study {10} to be kept in the refrigerator at home and brought back to clinic using cooling bags.

The domain literature search was used.

Safety risks for patients can be reduced by giving special attention to the management of patients with co-morbidities. Also the threshold of positivity of tests can influence the number of colonoscopies performed and thus safety.

Further education of GPs regarding the appropriateness of referrals for gFOBT in patients with major co-morbidities is important, because complications related to colonoscopy are increased in patients with major co-morbidites. {13}

• [NHS Centre for Reviews and Dissemination : Diagnostic Accuracy and Cost-Effectiveness of Faecal Occult Blood Tests Used in Screening for Colorectal Cancer: A Systematic Review, 2007] {8}

Changing the threshold for positivity (e.g. the number of windows required to show blue colouration on a Haemoccult slide) may change both the sensitivity and specificity of the test. Some studies stated that ‘any blue colour’ indicated a positive result, others specified that 2, 3 or more windows had to show a blue colouration to be positive, and some studies retested after what were considered ‘weak’ positive results. These differences in threshold will affect the observed positivity rate of the test, and as such, will impact on the proposed number of colonoscopies that would be required as a result of a screening programme with FOBT.

The domain literature search was used.

There were no safety risks for professionals found from literature.