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

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

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 …

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

Crc types

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

SUPPRESSOR OR CANONICAL PATHWAY -Fearon and Vogelstein model

MSI (MUTATOR) PATHWAY

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

Rationale for screening Most CRC are slow growing (doubling time of approx. 600 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

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

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

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

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

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

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

Colonoscopy

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

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

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

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.

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

The National Polyp Study 1418 patients Colonoscopy-removal of one or more polyps Mean follow-up of six years Incidence of colon cancer : -88-90 % 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

Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence 1693 subjects of both sexes, aged 40-69 years A total colon examination  1980-1987 Removal of at least one adenoma larger than 5 mm in diameter Mean follow up 10.5 years Citarda et al.Gut 2001

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

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

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

Endoscopic Polypectomy

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

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

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

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

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

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

Blind areas difficult to observe

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

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

Fuse-colonoscopy

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

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.

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

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

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

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

Thank you