Result card

  • SAF1: What kind of harms can use of FIT cause to the patient; what are the incidence, severity and duration of harms?
English

What kind of harms can use of FIT cause to the patient; what are the incidence, severity and duration of harms?

Authors: Agnes Männik, Irena Guzina, Petra Jandova, Leonor Varela Lema, Gerardo Atienza Merino

Internal reviewers: Matthias Schwenkglenks, Ingrid Wilbacher

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).

Summary table of selected references:Author, year

Type of reference

Title

Conclusions

HAS, 2013

{1}

National recommendation

HAS recommendation on colorectal screening and prevention

The overall morbidity related to colonoscopy is estimated to 5%. Major complications are rare.

Medical Services Advisory Committee, 2004 {4}

Assessment report

Faecal occult blood testing for population health screening

Occasional complications are associated with bowel preparation and sedation prior to colonoscopy.

Hewitson P, Glasziou P, Irwig L, Towler B, Watson E., 2007, update 2011

{3}

Cochrane systematic review

Screening for colorectal cancer using the faecal occult blood test, Hemoccult

The rate of perforation during colonoscopy is approximately 1 in 1,400.  Major bleedings occurred in 1 out of approximately 1100-1500 procedures. 

 

Quintero et al., 2012 {6}

Article

Colonoscopy versus Fecal Immunochemical Testing in Colorectal-Cancer Screening

Among 24 subjects[1] in the colonoscopy group, 12 (50%) expereinced bleeding, 10 (42%) hypotension or bradycardia, 1 (4%) perforation, and 1 (4%) low blood saturation.

Among 10 subjects[2] in the FIT group who had subsequent colonoscopy, 8 patients (80%) expereinced bleeding and 2 (20%) hypotension or bradycardia.

Guittet, L., et al., 2007 {7}

Article

Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population

A perforation of the gut occurred in one out of 644 patients screened by colonoscopy (0,2%).

Senore, C., et al., 2011

{5}

Article

Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting

The burden of bowel preparation was associated with a nearly five-fold increase in the occurrence of serious disturbances among people undergoing TC, as compared with FS.

 

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. 

Critical
Completely
Männik A et al. Result Card SAF1 In: Männik A et al. Safety In: Jefferson T, Cerbo M, Vicari N [eds.]. Fecal Immunochemical Test (FIT ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali; 2014. [cited 16 June 2021]. Available from: http://corehta.info/ViewCover.aspx?id=206

References