1. Colonoscopy in crc screening
NINA MARKOUTSAKI
Gastroenterologist
Specialised in Digestive Oncology
Diplôme Inter Universitaire (DIU) de Cancérologie Digestive – Ile-de- France,
Paris V, Université de Versailles

2. Colon cancer-Epidemiology
Colorectal cancer (CRC) is a common and lethal cancer
CRC is infrequent before age 40
CRC is the second most commonly diagnosed cancer in women and third most common in men
It has been estimated that more than 432,000 new CRC cases and 212,000 CRC deaths occur annually in Europe

3. Colon cancer-Epidemiology
The incidence of CRC is slightly higher in men than in women
The prevalence of colorectal polyps in the general population is roughly 30 %.
Screening provides benefit because …

5. Crc-aetiopathogenesis
Most colorectal cancers (CRCs) arise from adenomas
Neoplastic changes result from both inherited and acquired genetic defects
Approximately 20% have a familial or congenital mutation(s) -earlier stage of life.
80% are sporadic, with no obvious genetic causes-later in life
Rao,Yamada Front Oncol 2013
They tend to develop at an earlier stage of life
Sporadic cancers :thus, suggesting roles for environmental factors, for time and for accumulation of multiple yet specific genetic mutations and/or for epigenetic alterations

6. Crc types

7. Sporadic crc
Development of sporadic cancer is a slow, age-influenced process with progressive acquisition of genetic mutations and/or epigenetic alterations under the influence of environmental and other external factors.
Rao,Yamada Front Oncol 2013

8. SUPPRESSOR OR CANONICAL PATHWAY -Fearon and Vogelstein model

9. MSI (MUTATOR) PATHWAY

10. Risk of crc Increases with adenoma size, number, and histology
The polyp examined is representative of the individual’s propensity to form polyps and cancer
The number and types of lesions found will determine the appropriate interval for subsequent surveillance colonoscopy

11. Rationale for screening
Most CRC are slow growing (doubling time of approx days)
Adenoma-Carcinoma Sequence >10 years
Removal of premalignant adenomas can prevent CRC and removal of localized cancer may prevent CRC-related death
Cancers discovered by screening tend to be less advanced and associated with greater probability of curative resection

12. Adenoma-carcinoma sequence
Polypoid adenomas
Nonpolypoid adenomas (22-36% of adenomas)
-Flat
-Depressed
Hyperplastic polyps
Two-thirds of polyps are adenomas
Hyperplastic polyps account for most of the remaining polyps and are typically small (<1 cm) and distal

13. Screening for crc Stool-based tests
-Guaiac-based fecal occult blood test 
-Fecal immunochemical test 
-FIT-DNA 
The FIT-DNA is a multitargeted stool DNA test

14. Screening for crc Endoscopic and radiologic examinations -Colonoscopy
-CTC (Virtual colonoscopy)
-Flexible sigmoidoscopy +/- FIT or gFOBT

15. GUIDELINE RECOMMENDATIONS
Guideline recommendations vary, depending on :
- the prevalence of disease in a given population,
- the availability of resources,
- health care priorities,
-aggressiveness with which preventive health care is promoted

16. WORLDWIDE GUIDELINES European Union
U.S. Preventive Services Task Force
U.S. Multi-Society Task Force on Colorectal Cancer Screening and Surveillance
American Cancer Society
American College of Physicians
Canadian Cancer Society, Canadian Association of Gastroenterology
British Society of Gastroenterology

17. Screening-A suggested approach
Identifying a patient as average risk for CRC
Reviewing risks and benefits of screening options with the patients
Colonoscopy, for those, willing to undergo the procedure
Initial screening by FIT or CTC, for those, unable or unwilling to have a colonoscopy;
- if positive FIT or CTC, then colonoscopy, within 3 months

18. Colonoscopy

19. Why Colonoscopy ? Method of high sensitivity and specificity
Both detects and effectively removes pro-malignant and malignant lesions (Polyps, precursor of cancer)
Recommended by almost all international and national gastroenterology and cancer societies, as an initial screening modality

20. Colonoscopy for average risk population
Colonoscopy represents the most important diagnostic and therapeutic modality for CRC prevention and treatment.
Recommended to be performed every 10 years for individuals of average risk starting from the age of 50
 It is the final common pathway for all positive screening tests

21. Screening Colonoscopy for high risk population
Patients whose first-degree relatives developed colorectal cancer before the age of 50 years 
-at 40 years or 10 years before cancer was diagnosed in the youngest affected family member, whichever is earlier
Hereditary non polyposis syndrome (HNPCC/Lynch syndrome)
- at 20 to 25 years of age and every 1-3 years thereafter
Familial adenomatous Polyposis
-at puberty and every 1-2 years thereafter

22. Screening Colonoscopy for high risk population
Inflammatory Bowel Disease (IBD)-mainly UC
-Initial colonoscopy, 7- 8 years after the diagnosis of pancolitis and 12 to 15 years after the diagnosis of left-sided colitis. Every 2 years thereafter.

24. Evaluation of colonoscopy
Data from randomized controlled trials on the effects of screening colonoscopies on colorectal cancer (CRC) incidence and mortality, not available. 
Observational studies suggest that colonoscopy in the prior 10 years, reduced CRC incidence and mortality by over 60 %
Only 50% of eligible adults screened

25. The National Polyp Study
1418 patients
Colonoscopy-removal of one or more polyps
Mean follow-up of six years
Incidence of colon cancer :
% lower than in patients reported in other studies who had polyps that were not removed
-76 % lower than in the general population.
Winawer et al. N Engl J Med. 1993

26. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence
1693 subjects of both sexes, aged years
A total colon examination 
Removal of at least one adenoma larger than 5 mm in diameter
Mean follow up 10.5 years
Citarda et al.Gut 2001

27. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence
Results:
-Colonoscopic polypectomy substantially reduced the incidence of colorectal cancer in the cohort compared with that expected in the general population.(6 versus 17.7)
Citarda et al.Gut 2001

28. Reduced Risk of Colorectal Cancer Up to 10 Years After Screening, Surveillance, or Diagnostic Colonoscopy
Population-based case-control study
3148 patients with a first diagnosis of CRC
3274 subjects without CRC 
Detailed information on previous colonoscopy
Brenner et al.Gastroenterology 2014

29. Reduced Risk of Colorectal Cancer Up to 10 Years After Screening, Surveillance, or Diagnostic Colonoscopy
Results:
A previous colonoscopy was associated with a reduced subsequent risk of CRC, independently of the indication for the examination (1.7% vs 12.0%)
Colonoscopy was associated with a reduced risk of cancer in the right colon, regardless of the indication
Brenner et al.Gastroenterology 2014

30. Endoscopic Polypectomy

31. Colonoscopy-barriers
Risks
Availability
Cost
Inadequate knowledge or awareness of CRC risk
Compliance

32. Quality in colonoscopy
Vigorous bowel preparation
Cecal intubation rate (CIR)
Withdrawal time
Increased ADR
Complete resection rate
Complications
Patient satisfaction

33. Adenoma detection rate (adr)
The proportion of screening colonoscopic examinations performed by a physician that detect one or more adenomas
The estimation of adenoma detection rates should be now considered as a current standard of care for endoscopists

34. Adenoma Detection Rate and Risk of Colorectal Cancer and Death
Strong inverse association between the adenoma detection rate and the risk of interval cancer 
Every 1% increase in ADR, 3% decrease in the risk of interval CRC
Corley et al. N Engl J Med 2014

36. increased adr Cecal intubation Increased withdrawal time
Higher quality bowel prep
Antispasmodic use
Earlier procedure start
Greater colonoscopist experience

37. Colonoscopy-limitations
Location of polyps: 2/3 of missed polyps, on proximal aspect of haustral folds
12-24% of polyps in flexures and folds are missed
Nonpolypoid flat lesions may be missed.
Suboptimal bowel preparation
Endoscopists’ Training and Experience
Pickhardt et al.Ann Intern Med 2004
Pab et al. Gastrointestinal Endosc 2005

38. Blind areas difficult to observe

39. Safety of screening colonoscopy
An invasive procedure
The complication rate not over 1 %, in large series
-sedation related complications
-colon perforation
-post polypectomy bleeding
- bowel preparation can lead to
dehydration and electrolyte abnormalities

40. New tech colonoscopy High Definition Colonoscopy
Cap-assisted colonoscopy
Image enhanced colonoscopy (NBI, iScan , FICE)
FUSE colonoscopy
EndoRings/Endocuff colonoscopy
Third-Eye Retroscope

41. Fuse-colonoscopy

42. New tech colonoscopy
Majority of additionally detected adenomas are diminutive
Cost effectiveness
Better training to improve ADR with standard forward viewing colonoscopy

43. Take home messages
Colorectal cancer (CRC) is a common and lethal cancer
CRC is infrequent before age 40
Most colorectal cancers (CRCs) arise from adenomas
Before deciding how best to screen and when to initiate screening, clinicians should determine the individual patient's level of risk.

44. Take home messages
Colonoscopy recommended by almost all international and national gastroenterology and cancer societies, as an initial screening modality
Removal of premalignant adenomas can prevent CRC and removal of localized cancer may prevent CRC-related death
Colonoscopy is the final common pathway for all positive screening tests

45. Take home messages
Support for the role of colonoscopy in CRC prevention derives entirely from indirect evidence and observational studies
Colonoscopy reduces CRC incidence and mortality by over 60 %
Need to optimize the quality and effectiveness of colonoscopy

46. Take home messages
The estimated adenoma detection rates should be now considered as a current standard of care for endoscopists
Limitations to successful screening colonoscopy: the blind location of polyps, nonpolypoid flat lesions, poor bowel preparation and lack of endoscopists’ experience
New frontiers in screening colonoscopy will focus on improving colonoscopy techniques

47. Get the test.
Get the polyp.
Get the cure.

48. Thank you