Ignite Creation Date:
2024-05-06 @ 4:12 PM
Last Modification Date:
2024-10-26 @ 2:05 PM
Study NCT ID:
NCT04906343
Status:
UNKNOWN
Last Update Posted:
2021-09-23
First Post:
2021-05-10
Brief Title:
Endoscopic Surveillance in Serrated Polyposis Syndrome and Low-risk of Advanced Neoplasia
Sponsor:
Hospital Universitario de Móstoles
Organization:
Hospital Universitario de Móstoles
Study Overview
Official Title:
Endoscopic Surveillance in Patients With Serrated Polyposis Syndrome and Low-risk of Advanced Neoplasia
Status:
UNKNOWN
Status Verified Date:
2021-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The aim of the study is to determine if Serrated Poliposis Syndrome SPS patients with SPS criteria 2 with clearing phase achieved and without any advanced lesion or less than 5 relevant lesions at last colonoscopy have the same advanced neoplasia incidence in the surveillance colonoscopy at 2 or 3 years
Patients selected for the study will be randomised in two groups for the surveillance group 1 surveillance with colonoscopy in two years group 2 surveillance with colonoscopy in three years Randomization will be done at the database program RedCAP
All colonoscopies will be performed with high definition HD system and it will be the choice of the endoscopist whether to use chromoendoscopy with indigo carmine o virtual chromoendoscopy Protocol bowel preparation will be recommended by each centre Sedation will be prescribed and decided by the endoscopist during the examination
Data from all the resected and visualized lesions during the colonoscopy will be collected on the database A pathologist familiarized with serrated lesions will be in charge of the sample analysis Serrated lesions will be classified attending de WHO criteria for serrated lesions The investigators define advanced adenoma as adenomas 10 mm with villous histology andor with high grade of dysplasia HGD The investigators define advanced SL as any SL 10mm and any SL with dysplasia The investigators also define advanced neoplasia as any colorectal cancer CRC any advanced adenoma or advanced Serrated Lesions SL
Quality of bowel cleansing will be graded by each endoscopist following the Boston Bowel Preparation Scale This scale evaluates each segment ascending colon transverse colon and descending colon of the following form 0 segment of colon whose mucosa cannot be seen due to the existence of solid stools that cannot be eliminated 1 mucosa portion of a colonic segment that can be seen but other areas of the colonic segment are not seen either due to the presence of dirt feces or opaque liquid 2 existence of small amount of dirt small fragments of stool and or opaque liquid but the mucosa of the colonic segment can be seen well 3 all the mucosa of the colonic segment can be seen well without residual dirt small traces of stool or opaque liquid Patients with inadequate preparation when in any segment the score is 0 or 1 or the total score is less than 6 will be excluded from the study
During colonoscopy all complications as post-polypectomy bleeding perforation or cardio-respiratory events will be registered Those complications will be considered if surgery or hospital admission is required
Patients selected for the study will be randomised in two groups for the surveillance group 1 surveillance with colonoscopy in two years group 2 surveillance with colonoscopy in three years Randomization will be done at the database program RedCAP
All colonoscopies will be performed with high definition HD system and it will be the choice of the endoscopist whether to use chromoendoscopy with indigo carmine o virtual chromoendoscopy Protocol bowel preparation will be recommended by each centre Sedation will be prescribed and decided by the endoscopist during the examination
Data from all the resected and visualized lesions during the colonoscopy will be collected on the database A pathologist familiarized with serrated lesions will be in charge of the sample analysis Serrated lesions will be classified attending de WHO criteria for serrated lesions The investigators define advanced adenoma as adenomas 10 mm with villous histology andor with high grade of dysplasia HGD The investigators define advanced SL as any SL 10mm and any SL with dysplasia The investigators also define advanced neoplasia as any colorectal cancer CRC any advanced adenoma or advanced Serrated Lesions SL
Quality of bowel cleansing will be graded by each endoscopist following the Boston Bowel Preparation Scale This scale evaluates each segment ascending colon transverse colon and descending colon of the following form 0 segment of colon whose mucosa cannot be seen due to the existence of solid stools that cannot be eliminated 1 mucosa portion of a colonic segment that can be seen but other areas of the colonic segment are not seen either due to the presence of dirt feces or opaque liquid 2 existence of small amount of dirt small fragments of stool and or opaque liquid but the mucosa of the colonic segment can be seen well 3 all the mucosa of the colonic segment can be seen well without residual dirt small traces of stool or opaque liquid Patients with inadequate preparation when in any segment the score is 0 or 1 or the total score is less than 6 will be excluded from the study
During colonoscopy all complications as post-polypectomy bleeding perforation or cardio-respiratory events will be registered Those complications will be considered if surgery or hospital admission is required
Detailed Description:
Colorectal cancer CRC is the most frequent neoplasm in developed countries considering both sexes and is the second in terms of cancer mortality The incidence of the CRC is increasing in all developed countries Detection of precancerous lesions colon polyps or malignant lesions adenocarcinoma in early stages in screening programs improves the prognosis and decreases the mortality of these patients Serrated polyposis syndrome SPS is the most common colorectal polyposis syndrome and is characterized by the combination of large andor numerous serrated lesions SL throughout the colorectum There are three different types of SLs described hyperplastic polyps HP sessile serrated lesions SSL and traditional serrated adenomas TSA
In 2010 the world health organization WHO defined the clinical criteria for the SPS diagnosis criteria I any patient with 5 serrated lesions proximal to the sigma two of them 1 cm in size criteria II any first degree relative of a SPS patient with at least one serrated lesion criteria II any patient with 20 serrated lesions throughout the colon This criteria were reviewed in 2019 and criteria II was eliminated The new criteria are criteria 1 any patient with 5 SL proximal to the rectum all 5 mm in size with at least 2 lesions 10 mm in size criteria 2 any patient with 20 SL of any size distributed throughout the colon with 5 lesions proximal to the rectum
In recent years a new pathway in the development of colorectal adenocarcinoma have been described the serrated pathway It is associated with mutations in BRAF and KRAS genes the existence of hypermethylation in the promoter regions CpG island and microsatellite instability phenotype caused by methylation of the MLH-1 gene This new pathway has a faster progression from the serrated polyp to the CRC in comparison with the classic adenoma-carcinoma pathway hence the importance of detecting and removing these lesions in patients with SPS
CRC prevalence in patients diagnosed with SPS is 15-35 according to different studies and the probability at 5 years of developing a CRC is around 13-19 During surveillance the incidence of advanced neoplasia advanced adenoma or advanced serrated lesions at 3 years is 13 for adenomas and 42 for serrated lesions Risk factors for developing CRC and advanced neoplasia have been described in several studies One of these factors is the SPS criteria 2 which has been demonstrated as a low risk of CRC and advanced neoplasia during surveillance of SPS patients Detecting more than two sessile serrated lesions proximal to the spleenic flexure one sessile serrated lesion with high grade of dysplasia and the detection of advanced neoplasia in previous colonoscopies are all risk factors of developing advanced neoplasia during surveillance A recent multicentre prospective study established SPS patient surveillance according to lesions detected at last colonoscopy Individuals with at least one advanced adenoma an advanced serrated lesion or more than 5 relevant lesions sessile serrated lesions adenomas of any size or hyperplastic polyps more than 5 mm were followed at one year Patients with no lesions mentioned before were followed at 2 years with colonoscopy Advanced neoplasia incidence in 2 years recommendation surveillance was 156 compared with 244 in the 1 year recommendation surveillance CRC cumulative 5 years incidence was 13 Regarding SPS type the 5 years advanced neoplasia incidence was lower for patients with SPS criteria III of 2010 26 than for patients diagnosed with criteria I 53 or criteria I and III 59 In this study patients starting their surveillance with clearing phase achieved clear colon of all polyps 5mm and all polyps with the optical aspect of adenoma TSA or SSL were at low risk of advanced neoplasia than patients without this phase achieve prior to study inclusion HR 064 p0047
With all the above described the investigators can define a SPS patient with low risk of advanced neoplasia during surveillance those patients with SPS criteria 2 with clearing phase achieved and without any advanced lesion or less than 5 relevant lesions at last colonoscopy
The Spanish Society of Gastroenterology AEG recommends surveillance with colonoscopies in 1-3 years interval for SPS patient as it does the European Society of Digestive Oncology ESDO The European Society of Gastrointestinal Endoscopy ESGE recommends surveillance at 1 o 2 years depending on the last colonoscopy findings annually in case of any advanced adenoma or serrated lesion or 5 relevant lesions adenomas SSL or HP5mm were removed and two surveillance in all other cases The British Society of Gastroenterology BSG recommends annually surveillance for SPS patients until all serrated lesions are removed and then 2 year-surveillance All these Guidelines mention the limited evidence to support their recommendations and the need for prospective studies to evaluate them As well many authors have expressed the possibility of extending the surveillance to 3 or even 5 years in low risk patients
The aim of the study is to determine if SPS patients with SPS criteria 2 with clearing phase achieved and without any advanced lesion or less than 5 relevant lesions at last colonoscopy have the same advanced neoplasia incidence in the surveillance colonoscopy at 2 or 3 years
Patients selected for the study will be randomised in two groups for the surveillance group 1 surveillance with colonoscopy in two years group 2 surveillance with colonoscopy in three years Randomization will be done at the database program RedCAP
All colonoscopies will be performed with high definition HD system and it will be the choice of the endoscopist whether to use chromoendoscopy with indigo carmine o virtual chromoendoscopy Protocol bowel preparation will be recommended by each centre Sedation will be prescribed and decided by the endoscopist during the examination
Data from all the resected and visualized lesions during the colonoscopy will be collected on the database A pathologist familiarized with serrated lesions will be in charge of the sample analysis Serrated lesions will be classified attending de WHO criteria for serrated lesions The investigators define advanced adenoma as adenomas 10 mm with villous histology andor with high grade of dysplasia HGD The investigators also define advanced SL as any SL 10mm and any SL with dysplasia The investigators define advanced neoplasia as any CRC any advanced adenoma or advanced SL
Quality of bowel cleansing will be graded by each endoscopist following the Boston Bowel Preparation Scale This scale evaluates each segment ascending colon transverse colon and descending colon of the following form 0 segment of colon whose mucosa cannot be seen due to the existence of solid stools that cannot be eliminated 1 mucosa portion of a colonic segment that can be seen but other areas of the colonic segment are not seen either due to the presence of dirt feces or opaque liquid 2 existence of small amount of dirt small fragments of stool and or opaque liquid but the mucosa of the colonic segment can be seen well 3 all the mucosa of the colonic segment can be seen well without residual dirt small traces of stool or opaque liquid Patients with inadequate preparation when in any segment the score is 0 or 1 or the total score is less than 6 will be excluded from the study
During colonoscopy all complications as post-polypectomy bleeding perforation or cardio-respiratory events will be registered Those complications will be considered if surgery or hospital admission is required
SAMPLE SIZE CALCULATION This is a randomized controlled study for evaluating a non inferiority strategy in the surveillance of SPS type 2 patients between colonoscopy in 2 years and colonoscopy in 3 years with the incidence of advanced neoplasia as the principal aim of the study In the study from the Netherlands Bleijenberg and col the incidence of advanced neoplasia in patients at 2 years surveillance was of 15 The investigators assume an acceptable increase of advanced neoplasia at 3 years surveillance of 25 so the margin for no inferiority is 10 between the two groups Accepting the type I error with an unilateral contrast of 0025 beta risk of 02 power 80 and considering a 10 of lost patients 69 patients in each group 136 in total are needed to detect significance differences between the two groups
STUDY VARIABLES
Demographic variables Hospital identification number number assigned to each hospital and consecutive number of each patient date of birth sex SPS criteria according to WHO classification and actualized in2019 1 or 2 date of the last colonoscopy number and type of lesions resected at the last colonoscopy number of previous colonoscopies number of polyps removed so far low risk high risk and serrated lesions colon surgery yesno and type of surgery right colectomy left colectomy low anterior resection segmental colectomy or others smoker yesnoprev
Variables of the procedure date of the procedure bowel preparation according to BBPS scale 14 study arm Colonoscopy in2 yearsColonoscopy inn3 years number and description of lesions resected during the procedure describing its size shape according to Paris classification15 location of the lesions distance to the anal margin Inspection time in each exploration with stopwatch and without counting the therapeutic moments Complications during the procedure bleeding perforation or cardio-respiratory events
NECESSARY RESOURCES
The colonoscopy and polypectomy will be done in the usual clinical care practice
This protocol does not require additional funding The explorations will be carried out by the researchers who are staff doctors of the Digestive Endoscopy Units The effort the minimum marginal expenses that may lead to the prolongation of the exploration and the collection of data will be assumed by the researchers and the Digestive Endoscopy Units
ETHICAL CONSIDERATIONS
This protocol follows the ethical principles of non-malfeasance beneficence autonomy and justice included in the Declaration of Helsinki last update Seoul 2008 17 as well as in law 412002 on patient autonomy18 and research law 142007 biomedical19 The personal and clinical data of the patients will be anonymized
In 2010 the world health organization WHO defined the clinical criteria for the SPS diagnosis criteria I any patient with 5 serrated lesions proximal to the sigma two of them 1 cm in size criteria II any first degree relative of a SPS patient with at least one serrated lesion criteria II any patient with 20 serrated lesions throughout the colon This criteria were reviewed in 2019 and criteria II was eliminated The new criteria are criteria 1 any patient with 5 SL proximal to the rectum all 5 mm in size with at least 2 lesions 10 mm in size criteria 2 any patient with 20 SL of any size distributed throughout the colon with 5 lesions proximal to the rectum
In recent years a new pathway in the development of colorectal adenocarcinoma have been described the serrated pathway It is associated with mutations in BRAF and KRAS genes the existence of hypermethylation in the promoter regions CpG island and microsatellite instability phenotype caused by methylation of the MLH-1 gene This new pathway has a faster progression from the serrated polyp to the CRC in comparison with the classic adenoma-carcinoma pathway hence the importance of detecting and removing these lesions in patients with SPS
CRC prevalence in patients diagnosed with SPS is 15-35 according to different studies and the probability at 5 years of developing a CRC is around 13-19 During surveillance the incidence of advanced neoplasia advanced adenoma or advanced serrated lesions at 3 years is 13 for adenomas and 42 for serrated lesions Risk factors for developing CRC and advanced neoplasia have been described in several studies One of these factors is the SPS criteria 2 which has been demonstrated as a low risk of CRC and advanced neoplasia during surveillance of SPS patients Detecting more than two sessile serrated lesions proximal to the spleenic flexure one sessile serrated lesion with high grade of dysplasia and the detection of advanced neoplasia in previous colonoscopies are all risk factors of developing advanced neoplasia during surveillance A recent multicentre prospective study established SPS patient surveillance according to lesions detected at last colonoscopy Individuals with at least one advanced adenoma an advanced serrated lesion or more than 5 relevant lesions sessile serrated lesions adenomas of any size or hyperplastic polyps more than 5 mm were followed at one year Patients with no lesions mentioned before were followed at 2 years with colonoscopy Advanced neoplasia incidence in 2 years recommendation surveillance was 156 compared with 244 in the 1 year recommendation surveillance CRC cumulative 5 years incidence was 13 Regarding SPS type the 5 years advanced neoplasia incidence was lower for patients with SPS criteria III of 2010 26 than for patients diagnosed with criteria I 53 or criteria I and III 59 In this study patients starting their surveillance with clearing phase achieved clear colon of all polyps 5mm and all polyps with the optical aspect of adenoma TSA or SSL were at low risk of advanced neoplasia than patients without this phase achieve prior to study inclusion HR 064 p0047
With all the above described the investigators can define a SPS patient with low risk of advanced neoplasia during surveillance those patients with SPS criteria 2 with clearing phase achieved and without any advanced lesion or less than 5 relevant lesions at last colonoscopy
The Spanish Society of Gastroenterology AEG recommends surveillance with colonoscopies in 1-3 years interval for SPS patient as it does the European Society of Digestive Oncology ESDO The European Society of Gastrointestinal Endoscopy ESGE recommends surveillance at 1 o 2 years depending on the last colonoscopy findings annually in case of any advanced adenoma or serrated lesion or 5 relevant lesions adenomas SSL or HP5mm were removed and two surveillance in all other cases The British Society of Gastroenterology BSG recommends annually surveillance for SPS patients until all serrated lesions are removed and then 2 year-surveillance All these Guidelines mention the limited evidence to support their recommendations and the need for prospective studies to evaluate them As well many authors have expressed the possibility of extending the surveillance to 3 or even 5 years in low risk patients
The aim of the study is to determine if SPS patients with SPS criteria 2 with clearing phase achieved and without any advanced lesion or less than 5 relevant lesions at last colonoscopy have the same advanced neoplasia incidence in the surveillance colonoscopy at 2 or 3 years
Patients selected for the study will be randomised in two groups for the surveillance group 1 surveillance with colonoscopy in two years group 2 surveillance with colonoscopy in three years Randomization will be done at the database program RedCAP
All colonoscopies will be performed with high definition HD system and it will be the choice of the endoscopist whether to use chromoendoscopy with indigo carmine o virtual chromoendoscopy Protocol bowel preparation will be recommended by each centre Sedation will be prescribed and decided by the endoscopist during the examination
Data from all the resected and visualized lesions during the colonoscopy will be collected on the database A pathologist familiarized with serrated lesions will be in charge of the sample analysis Serrated lesions will be classified attending de WHO criteria for serrated lesions The investigators define advanced adenoma as adenomas 10 mm with villous histology andor with high grade of dysplasia HGD The investigators also define advanced SL as any SL 10mm and any SL with dysplasia The investigators define advanced neoplasia as any CRC any advanced adenoma or advanced SL
Quality of bowel cleansing will be graded by each endoscopist following the Boston Bowel Preparation Scale This scale evaluates each segment ascending colon transverse colon and descending colon of the following form 0 segment of colon whose mucosa cannot be seen due to the existence of solid stools that cannot be eliminated 1 mucosa portion of a colonic segment that can be seen but other areas of the colonic segment are not seen either due to the presence of dirt feces or opaque liquid 2 existence of small amount of dirt small fragments of stool and or opaque liquid but the mucosa of the colonic segment can be seen well 3 all the mucosa of the colonic segment can be seen well without residual dirt small traces of stool or opaque liquid Patients with inadequate preparation when in any segment the score is 0 or 1 or the total score is less than 6 will be excluded from the study
During colonoscopy all complications as post-polypectomy bleeding perforation or cardio-respiratory events will be registered Those complications will be considered if surgery or hospital admission is required
SAMPLE SIZE CALCULATION This is a randomized controlled study for evaluating a non inferiority strategy in the surveillance of SPS type 2 patients between colonoscopy in 2 years and colonoscopy in 3 years with the incidence of advanced neoplasia as the principal aim of the study In the study from the Netherlands Bleijenberg and col the incidence of advanced neoplasia in patients at 2 years surveillance was of 15 The investigators assume an acceptable increase of advanced neoplasia at 3 years surveillance of 25 so the margin for no inferiority is 10 between the two groups Accepting the type I error with an unilateral contrast of 0025 beta risk of 02 power 80 and considering a 10 of lost patients 69 patients in each group 136 in total are needed to detect significance differences between the two groups
STUDY VARIABLES
Demographic variables Hospital identification number number assigned to each hospital and consecutive number of each patient date of birth sex SPS criteria according to WHO classification and actualized in2019 1 or 2 date of the last colonoscopy number and type of lesions resected at the last colonoscopy number of previous colonoscopies number of polyps removed so far low risk high risk and serrated lesions colon surgery yesno and type of surgery right colectomy left colectomy low anterior resection segmental colectomy or others smoker yesnoprev
Variables of the procedure date of the procedure bowel preparation according to BBPS scale 14 study arm Colonoscopy in2 yearsColonoscopy inn3 years number and description of lesions resected during the procedure describing its size shape according to Paris classification15 location of the lesions distance to the anal margin Inspection time in each exploration with stopwatch and without counting the therapeutic moments Complications during the procedure bleeding perforation or cardio-respiratory events
NECESSARY RESOURCES
The colonoscopy and polypectomy will be done in the usual clinical care practice
This protocol does not require additional funding The explorations will be carried out by the researchers who are staff doctors of the Digestive Endoscopy Units The effort the minimum marginal expenses that may lead to the prolongation of the exploration and the collection of data will be assumed by the researchers and the Digestive Endoscopy Units
ETHICAL CONSIDERATIONS
This protocol follows the ethical principles of non-malfeasance beneficence autonomy and justice included in the Declaration of Helsinki last update Seoul 2008 17 as well as in law 412002 on patient autonomy18 and research law 142007 biomedical19 The personal and clinical data of the patients will be anonymized
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None