Download - Colorectal Cancer Screening
![Page 1: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/1.jpg)
Update in Colorectal Cancer Screening
Douglas K. Rex, M.D.Indiana University
Medical CenterIndianapolis, IN
![Page 2: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/2.jpg)
Colorectal Cancer – Molecular Basis
Pathway Frequency Genes MSI Precursor Speed
CIN 65-70% APCK-rasp53
No Adenoma Slow
Lynch 3% MLH1MLH2MLH6PMS2
Yes Adenoma Fast
CIMP 30-35% BRAF Sometimes Serrated Can be fast
![Page 3: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/3.jpg)
Minimal Terminology of Serrated Lesions (WHO)
§ Hyperplastic polyp (HP)§ Sessile serrated adenoma/polyp (SSA/P)
– With cytological dysplasia– Without cytological dysplasia
§ Traditional serrated adenoma (TSA)
![Page 4: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/4.jpg)
Therefore
§ The WHO recommends that the term “serrated adenoma” always be preceded by a qualifier:
– Sessile serrated adenoma/polyp (SSA/P)– Traditional serrated adenoma (TSA)
![Page 5: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/5.jpg)
Features of major categories of serrated lesions
WHO classification
Prevalence Shape Distribution Malignant potential
Hyperplastic polyp
Very common
Sessile/flat Mostly distal Very low
Sessile serrated adenoma/polyp
Common Sessile/flat 80% proximal Significant
Traditional serrated adenoma
Rare Sessile/ pedunculated
Mostly distal Significant
![Page 6: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/6.jpg)
Pathologic differentiation of SSA/P from HP
§ HP § SSA/P
![Page 7: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/7.jpg)
SSA/P without and with cytological dysplasia
§ SSA/P without dysplasia
§ SSA/P with dysplasia
![Page 8: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/8.jpg)
2416 SSA/Ps
mean age§ SSA/P 61y§ SSA/P with LGD 66y§ SSA/P with HGD 72y§ SSA/P with cancer 76y
• Lash J Clin Pathol 2010;63:681-6
![Page 9: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/9.jpg)
The serrated pathway
Hyperplastic polyp ? ↓ ? Sessile serrated adenoma/polyp ↓ probably slow SSA/P with cytologic dysplasia ↓ sometimes fast CIMP colon cancer
![Page 10: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/10.jpg)
So……….
§ SSA/P is the main precursor of CIMP-high CRC§ No reliable way to distinguish HP from SSA/P
endoscopically• Kimura et al AJG 2012: “Type O” pit
§ Agreement for pathologists distinguishing HP from SSA/P is moderate
§ Most large serrated lesions in the proximal colon are SSA/P
§ SSA/P with cytological dysplasia is a dangerous lesion
![Page 11: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/11.jpg)
Clinical associations of serrated polyps with CIMP-high CRCs
§ SSA/P histology (vs hyperplastic)§ Proximal location (vs distal) of serrated
lesions§ Size (big vs small) of serrated lesions§ Number (more vs fewer) of serrated
lesions
![Page 12: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/12.jpg)
Can screening tests detect serrated lesion ?
Sensitivity for serrated lesions
Colonoscopy highly variable
FIT ?Fecal DNA ?CT colonography ?Flex sig ?Capsule colonoscopy ?Serum assays ?
![Page 13: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/13.jpg)
Colorectal Cancer Screening Tests
§ Non-invasive tests§ gFOBT √§ FIT √
§ Fecal DNA§ Serum tests
§ Imaging tests§ Colonoscopy √
§ Flex sig (seldom used)
§ CT colonography (seldom used)
§ Capsule colonoscopy (not FDA approved)
![Page 14: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/14.jpg)
How do we achieve excellence in screening?
§ Utilize high quality colonoscopists– Should be able to quote ADR– Should see split dose preparations– Should see consistent photographic
documentation of cecal intubation– Should see appropriate use of follow up
exams§ Switch from gFOBT to FIT
– Avoid exams on digital rectals
![Page 15: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/15.jpg)
RCT of FIT vs g-FOBT
§ 20,623 screenees§ RCT of FIT (OC-
Sensor) vs g-FOBT (HII)
§ Adherence 59.6% vs 46.9% (HII)
§ Positivity 5.5% vs 2.4% (HII)
Van Rossum; GASTRO 2008;135:82
![Page 16: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/16.jpg)
Variable Performance of FITs
Hundt Ann Intern Med 2009;150:162-9
![Page 17: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/17.jpg)
Performance of the Fecal DNA Versions 1.0, 1.1, 2.0
1.0 1.1 2.0
![Page 18: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/18.jpg)
Septin 9 performance
§ 7000 patient sceening trial: manuscript still not published
§ 62% sensitivity for cancer– Sensitivity lower for early stage cancer
§ No sensitivity for adenomas§ 88% specificity
![Page 19: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/19.jpg)
Fecal DNA testing vs Septin 9Ahlquist CGH 2012;10:272
Fecal DNA test Septin 9
Sensitivity for cancer Stage I-III
91% 50%
Sensitivity for cancerStage IV
75% 88%
Sensitivity for large adenomas
82% 14%
specificity 93% 73%
![Page 20: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/20.jpg)
CT colonography
§ Not approved by the USPSTF– Radiation risk– Extracolonic findings
§ Not approved by CMS– Insufficient data in the elderly– Less cost-effective than colonoscopy
![Page 21: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/21.jpg)
First RCT of Colonoscopy vs CTCNetherlands (abstract 353;DDW 2011)
§ Colonoscopy: 5,924 invited§ Adherence: 21%
§ Advanced adenomas per 100 participants:
– 8.4§ Advanced adenomas per
100 invitees:
– 1.7
§ CTC: 2,920 invited§ Adherence: 32%§ Advanced adenomas per
100 participants:
– 5.2§ Advanced adenomas per
100 invitees:
– 1.7
![Page 22: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/22.jpg)
Expected vs actual burden- prep
§ Colonoscopy § CTC
![Page 23: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/23.jpg)
Expected vs Actual burden - procedure
§ Colonoscopy § CT colonography
![Page 24: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/24.jpg)
Capsule colonoscopy
§ Not FDA approved§ PillCam 2
– Angle of view 172° from each end– Variable frame speed (4-35 fps)
§ Sensitivity > 80% for polyps ≥ 6mm§ Specificity < 80%§ Requires an extensive bowel preparation
![Page 25: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/25.jpg)
Colonoscopy
![Page 26: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/26.jpg)
Operator dependence of screening tests
§ Low (good)§ Fecal DNA§ FIT
– Commercial variability
§ ? gFOBT– Interpretation– Digital exams
§ High (bad)§ Colonoscopy§ Flex sig
§ CT colonography§ Capsule
colonoscopy
![Page 27: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/27.jpg)
Flat Lesions – Paris Classification
![Page 28: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/28.jpg)
Pre-cancerous lesions in the colo-rectum: the basics
Lesion Paris shape Distribution Prevalence Pathology
Traditional adenomatous polyps
1p
1s
Left
Throughout
Low
Common
Mostly LGD
Mostly LGD
Flat adenomas(lesions)
2a Greater to right
Common Mostly LGD
Sessile serrated adenoma (polyp)
1s or 2a Right colon Common Distinction from HP may not be reliable
TSA 1s or 1p Left colon rare Uncertain
Depressed (adenomas)
2c2a + 2c2c+ 2a
Greater to right
rare ↑↑HGD and invasive CA
![Page 29: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/29.jpg)
Residual risk after colonoscopy:right vs left colon
![Page 30: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/30.jpg)
Associations with interval cancers
§ Serrated associations§ Features of interval cancers
– Proximal location– MSI positive – CIMP positive
§ Other associations§ Colonoscopy by
non-GI doctors§ Doctors with low
ADRs§ Low cecal
intubation rates§ Low polypectomy
rates§ Indication of FOBT
vs screening§ Incomplete
polypectomy
![Page 31: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/31.jpg)
The Adenoma Detection Rate
§ % of persons age ≥ 50 undergoing screening colonoscopy with ≥ 1 adenoma detected and removed
– Rex et al (USMSTF) 2002• AJG 2002;97:1296
– Rex et al (ACG/ASGE Task Force on Quality) 2006• GIE 2006;63:S16
![Page 32: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/32.jpg)
Operator dependence – cancer prevention
Kaminski et al NEJM2010;362:1795-803
Adenoma detection rate (ADR)
Hazard ratio
< 11% 10.94
11.0 14.9% 10.75
15.0-19.9% 12.50
![Page 33: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/33.jpg)
Polypectomy rates (relative to rates ≤ 10%) – Residual right colon cancer
![Page 34: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/34.jpg)
Residual right colon protectionSingh, H et al GASTRO 2010;139:1128-37
![Page 35: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/35.jpg)
Right colon cancers after colonoscopyBaxter et al GASTRO 2011;140:65-72
![Page 36: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/36.jpg)
Variable detection of adenomas among GI docs
Number of doctors
Lowest ADR Highest ADR Range
BarclayIllinois2006
12 9.4% 32.7% 3.5
ChenIndiana2007
9 15.5% 41.1% 2.7
ImperialeIndiana2009
25 7% 44% 6.3
ShaukatMinnesota2009
51 10% 39% 3.9
![Page 37: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/37.jpg)
Variable detection of proximal colon serrated lesions among GI docs
Number of doctors
Lowest proximal colon serrated lesion
detection rate
Highest proximal colon serrated lesion detection rate
Range
HetzelBoston 13 1.1% 7.6% 6.9
KahiIndiana 15 1% 18% 18
![Page 38: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/38.jpg)
What underlies variable detection?
§ Training– Lesion recognition– Withdrawal technique– Withdrawal time
§ Personality– Poor documentation of procedures
§ Visual gaze patterns§ Withdrawal time
![Page 39: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/39.jpg)
Flat adenoma
§ White light § Narrow-band imaging
![Page 40: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/40.jpg)
Sessile serrated polyp
§ White light § Narrow-band imaging
![Page 41: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/41.jpg)
Serrated lesions
![Page 42: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/42.jpg)
Serrated lesion
![Page 43: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/43.jpg)
Depressed lesion
![Page 44: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/44.jpg)
Depressed lesions
![Page 45: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/45.jpg)
Pseudodepression (2a dip)
![Page 46: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/46.jpg)
Bowel Preparation and Polyp Detection Rates
Adequate Inadequate Completion (%) 90.4 71.1*Time to cecum (min) 11.9 16.1*Withdrawal time (min) 9.8 11.3* Any adenoma 29.4 23.9* Adenoma >1 cm (%) 6.4 4.3*
Froehlich et al. Gastrointest Endoscop. 2005;61:378-384.
*P<0.05 for all measures.
Europe (N=5,832)
![Page 47: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/47.jpg)
Split-Dosing Provides More Satisfactory Results
Than Traditional Dosing (cont)
47
Group A = 4 L of PEG on the night before the procedure; Group B = 2 L of PEG on the evening before and 2 L on the morning of the procedure.
Reprinted from Aoun et al. Gastrointest Endosc. 2005;62(2):213-218.
Perc
ent
56.2
43.8
76.5
23.5
0
10
20
30
40
50
60
70
80
90
Satisfactory Unsatisfactory
Group AGroup B
Perc
ent
4.1
39.7
50.7
5.54.4
19.1
44.1
32.4
0
10
20
30
40
50
60
Poor Fair Good Excellent
Group AGroup B
![Page 48: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/48.jpg)
Efficacy of Suprep in 2 studies
§ Study 1 OSS PEG-EASuccess 82.4% 80.3%Excellent 44.6% 37.3%Good 37.8% 43.0% Fair 11.4% 16.1%Poor 4.7% 3.1%
Mean 3.24 3.15 p 0.28Adequate 94% 95%
§ Study 2 OSS PEG-EASuccess 97.2% 95.6%Excellent 63.3% 52.5%Good 33.9% 43.2%Fair 1.7% 3.3%Poor 1.1% 1.1% p 0.043Mean 3.59 3.47 p 0.05Adequate 99% 99%
![Page 49: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/49.jpg)
The impact of split dosing
SplitNot split
![Page 50: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/50.jpg)
Arguments AgainstSplit-Dosing Regimens
§ Inconvenient to the patient– Unlikely to be a factor once the process is
explained to the patient– Patients not more likely to be incontinent en
route to the endoscopy unit§ Anesthesiologists will not allow split-
dosing– Clear liquids allowed up until 2 hours prior
to sedation50
![Page 51: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/51.jpg)
How do we judge preps?
§ Efficacy– Split or same day dosing
§ Safety– Sodium phosphate use dramatically
decreased– Safe preps:
• PEG-ELS (Golytely etc) and SF-ELS (Nulytely)• Sodium sulfate (SuPrep)
§ Tolerability– Split dosing– Low volume– Better taste
![Page 52: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/52.jpg)
How to achieve effective preparation
§ Split dose all preps§ Low volume preps appropriate for routine
patients without severe constipation, on anti-motility agents
§ Have fall back approach for patients with clinical factors or proven track record of being hard to prepare
§ Discuss importance of preparation in your written instructions
§ Give clear written instructions
![Page 53: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/53.jpg)
What makes up good detection?
§ Bowel preparation§ Adequate time § Technique:
– Looking behind folds– Cleaning up– Adequate distention
§ Central gaze in the monitor§ Other factors:
– Personality?
![Page 54: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/54.jpg)
Withdrawal technique
![Page 55: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/55.jpg)
Right colon retroflexion
![Page 56: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/56.jpg)
Are there technical solutions to ADR & variable detection?
§ Flat lesions Effective?– Chromoendoscopy yes– NBI no– FICE no– iScan limited data– Autofluorescence mixed results– High definition mixed results
§ Hidden mucosa – Cap-fitted mixed results– Third-eye maybe
![Page 57: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/57.jpg)
Conclusion regarding technical solutions
§ Any gains in detection from technical solutions are much smaller than the variations in detection between examiners using white light
§ More study in low detectors needed
![Page 58: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/58.jpg)
Excellence in colonoscopy
§ Use effective bowel preparation regimens § Achieve high cecal intubation rates safely
and document with landmarks and photography
§ Examine carefully; know the full spectrum of precancerous lesions in the colon
– Know your ADR– You should see proximal colon serrated
lesions on a regular basis§ Follow the recommended screening and
surveillance intervals
![Page 59: Colorectal Cancer Screening](https://reader033.vdocuments.us/reader033/viewer/2022042719/568c0f551a28ab955a93b57f/html5/thumbnails/59.jpg)
How do we achieve excellence in screening?
§ Utilize high quality colonoscopists– Should be able to quote ADR– Should see split dose preparations– Should see consistent photographic
documentation of cecal intubation– Should see appropriate use of follow up
exams§ Switch from gFOBT to FIT
– Avoid exams on digital rectals