Colon Cancer Sreening Recommendations Jose M Nieto DO FACP FACG AGAF FASGE Borland Groover Clinic

No financial disclosures

Outline 1. Review SCREENING recommendations 2. Colon Polyps A. Non-neoplastic polyps B. Neoplastic polyps i. Serrated polyps ii. Adenomatous polyps 3. SURVEILLANCE recommendations A. Low-risk adenomas B. High-risk adenomas C. Serrated polyps 4. Quality indicators for Colonoscopy 5. Emerging technologies A. Stool DNA testing B. CT Colonography 6. Summary

Colorectal Cancer COMMON PROBLEM: GOOD NEWS: 3rd incident cancer (150,000/yr) 2nd cancer mortality (50,000/yr) Lifetime incidence 5% GOOD NEWS: Incidence & Mortality is declining 53% reduction due to screening (Edwards BK, Cancer 2010) 1987-2010: ¼ - ½ million cases prevented (Yang DX, Cancer 2014) Other reasons: decreased exposure to risk factors improved therapy

CRC Screening GOAL: Decrease mortality by decreasingn incidence of advanced disease 5-yr survival (%) LOCALIZED (bowel wall) 90 REGIONAL (LNs) 68 DISTANT (metastases) 10 EARLY DETECTION: PREVENTION: Detection / removal adenomas

CRC Screening Guidelines American Cancer Society (1st in 1980) USPSTF ACR USMSTF (2012 SURVEILLANCE) ACS-USMSTF-ACR (2008 SCREENING) ACG NCCN ACP stetements Council of European Union

CRC Screening Guidelines 2008 ACS-MSTF-ACR Primary goal: PREVENTION Sensitive test @single point in time preferred over repeated testing Start age 50 Stop when life expectancy <10 yrs STOOL BASED TESTING: gFOBT, iFOBT, sDNA STRUCTURAL TESTING: RADIOLOGICAL: DCBE CTC ENDOSCOPIC: Flexible Sigmoidoscopy Colonoscopy

CRC Screening Guidelines 2008 ACS-MSTF-ACR Early Detection / Prevention: Colonoscopy CTC FSIG DCBE Early Detection: gFOBT iFOBT sDNA q10 yrs q5 yrs (Colonoscopy if >6 mm) q5 yrs q1 yr q? 2008 USPSTF: FOBT q1 yr FSIG q5 yrs + FOBT q3 yrs Colonoscopy q10 yrs

Colon Polyps Non-Neoplastic Polyps Neoplastic Polyps Hyperplastic Mucosal Inflammatory pseudopolyps Submucosal (lipomas, fibromas, GIST) Hamartomatous Juvenile polyposis Peutz-Jeghers Cronkhite-Canada syndrome Neoplastic Polyps Serrated Polyps Adenomatous Polyps Colon Cancer-Post Curative surgery

Non-Neoplastic Polyps 1. Hyperplastic polyp 2. Inflammatory pseudopolyps 3. Submucosal (lipomas, fibromas, GIST)

Non-Neoplastic Polyps HAMARTOMAS Juvenile Polyposis Syndrome Peutz-Jeghers Syndrome Cronkhite-Canada Syndrome

Neoplastic Polyps Serrated Polyps Adenomatous/Tubulovillous Polyps

Serrated Polyps Hyperplastic Polyps (non-neoplastic) Typically <5mm in RS No increase in CRC No increase in proximal neoplasia If large > 10mm or proximal precursor to SSA/P & progression to CRC increased risk of synchronous advanced adenoma & multiple small adenomas increased risk of metachronous adenomas Serrated Polyposis Syndrome (SPS) WHO Criteria: > 5 serrated proximal colon (> 2 @ > 10mm) > 1 serrated proximal colon + FH of SPS > 20 serrated polyps Annual colonoscopy recommended (increased risk CRC)

Serrated Polyps Sessile Serrated Adenoma/Polyp (SSA/P) Typically in proximal colon Typically lack classic dysplasia Foci of classic DYSPLASIA & foci CANCER can occur Traditional Serrated Adenoma (TSA) Typically in rectosigmoid Diffuse but mild DYSPLASIA SSA/Ps & TSAs = Significant malignant potential Manage like adenomas Sessile w indistinct borders (must ensure complete excision) Thought to disproportionately cause INTERVAL CANCERS

Adenomatous Polyps ⅔ of all polyps >95% CRC arises from adenomas; <5% adenomas lead to CRC Prevalence: 30% at baseline (30-50% will have synchronous) 4% Advanced adenoma at baseline (8% > age 65) Advanced Adenomas: > 10 mm / HGD / Villous features FOCAL CANCER RISK: Villous histology Polyp size HGD METACHRONOUS ADENOMA RISK: # of polyps (> 3 ) Lifetime polyps Polyp size (20% when > 20 mm)

Surveillance Guidelines 2012 USMSTF (Endorsed by AGA, ASGE, ACG, ACS, & ACR) Risk Stratification LRAs: 1-2 TA <10mm HRAs: Villous histology HGD Adenoma >10 mm >3 small adenomas

Baseline: NO POLYPS 2012 USMSTF RECOMMENDATION: 10 yrs QUALITY of EVIDENCE: Moderate STUDY n 5 yr AA (%) 2007 VA Co-Op 291 2.4 2008 Imperiale 1256 1.3 2009 Leung 370 1.4 2010 Brenner 115 4.4 2010 US Vets 86 7 2011 Korean 1242 2 2009 PLCOC 318 5.3 (@6-7 yrs) Advanced Adenomas @5 yrs: 1.3-2.4% (baseline 4-10%) CAVEAT: FDR w CRC <age 60 5yr interval Concern for 10yr interval: 3 Canadian population studies: 9% of CRC are INTERVAL cancers most occur 1-5 yrs from baseline exam Importance of HIGH QUALITY examination

Baseline: Distal HPs <10mm 2012 USMSTF RECOMMENDATION: 10 yrs QUALITY of EVIDENCE: Moderate HPs are very common: benign lesions no increased synchronous / metachronous adenomas Polyp Size (mm) % HPs 1-5 50 6-9 27.9 >10 mm 13.7

Baseline: 1-2 Adenomas <10mm 2012 USMSTF RECOMMENDATION: 5-10 yrs QUALITY of EVIDENCE: Moderate STUDY n 5yr AA (%) 2007 VA Co-Op 291 4.6 2008 PPT 1905 5 2010 US Vets 86 5.2 2011 Korean 1242 2.4 2009 PLCOC 318 5.3 (@6-7 yrs) Baseline AA: 4-10% Best to do 5-year interval

Baseline: 3-10 Adenomas <10mm 2012 USMSTF RECOMMENDATION: 3 yrs QUALITY of EVIDENCE: Moderate 2009 NCI Pooling Study # Polyps

Surveillance Guidelines 2012 USMSTF Risk Stratification LRAs: 1-2 TA <10mm HRAs: Villous histology HGD Adenoma >10 mm >3 small adenomas 2010 British Gastro Society: LRAs 1-2 TA <10mm IRAs Adenoma >10 mm 3-4 small adenomas HRAs >5 small adenomas >3 adenomas w 1 >10mm

Baseline: >10 Adenomas <10mm 2012 USMSTF RECOMMENDATION: <3 yrs QUALITY of EVIDENCE: Moderate Consider 1yr colonoscopy Consider HEREDITARY syndromes

High (size) / Mod (histo) Baseline: >1 Adenoma >10mm, or Adenoma w villous features, or HGD 2012 USMSTF RECOMMENDATION: 3 yrs QUALITY of EVIDENCE: High (size) / Mod (histo) STUDY Feature Surveillance AA (%) 2009 NCI Pooling Study (3-5 yrs) 10-19 mm 15.9 >20 mm 19.3 2007 VA Co-Op (5 yrs) >10 mm 15.5 TVA 16.8 16.1 LARGE POLYPS: If complete excision is questioned...early f/u recommended Risk of HGD does not appear independent: Size & Histology

Baseline: SERRATED POLYPS 2012 USMSTF RECOMMENDATION: 3-5 yrs QUALITY of EVIDENCE: Low RISK FACTORS: SIZE: >10mm HISTO: Sessile serrated > HP SSA/P w dysplasia > SSA/P w/o dysplasia Location: Prox SC > distal SC Recommendations: SSA/P > 10mm SSA/P w dysplasia Traditional serrated adenomas SSA/P <10mm w/o dysplasia HRA-like: 3 yrs LRA-like: 5 yrs

2nd Surveillance Guidelines 2012 USMSTF Baseline Surveillance 1st 2nd LRA Neg 10 yrs ** 5 yrs HRA 3 yrs ** LRA @ Baseline Neg 1st colon 2.8 - 4.9% AA @ 3-5 yrs Consider 5yr surveillance rather than 10

Colonoscopy Quality Indicators Adenoma detection rate Avg. risk: 30.2% (22-58%) Heitman SJ, Clin Gastro Hep 2009 40% w High Definition Colonoscopes Cecal intubation rate (Adherence to surveillance guidelines) Overutilization Underutilization Monitoring of bowel preparation Inadequate -----> 35% adenoma & 36% AA miss rate at 1 yr USMSTF: Inadequate: repeat < 1yr Fair but adequate: repeat 5 yrs (OK to detect >5 mm)

Colonoscopy: Imperfect Gold Std Back-to-back colonoscopy in 183 patients Rex DK, Gastroenterol 1997 Polyp Size (mm) Miss Rate (%) < 5 27 6-9 13 >10 mm 6 CTC trials: Segmental Unblinding Polyp Size (mm) Miss Rate (%) >10 mm 12-17

Interval Cancers Majority due to missed lesions Directly related to quality of exam Incomplete polyp resection 19-27% occur in same colon segment polyps >20 mm ---> 18% residual adenoma Biologically different More proximal Increased microsatellite instability (mismatch repair) CIMP +ve (CpG Island Methylator Phenotype) ? significant role from SSA/P

Stool DNA Testing Approved 2014 Earlier test withdrawn from mrkt Immunochemical assay (iFOBT) added Molecular assay for DNA mutations & methylation biomarkers COLOGUARD Detects 92% of CRC Detects 42% adenomas Contraindications: Hx of ADENOMAS, CRC FHx of CRC Diarrhea, hemorrhoids, fissures 2014 FIT v sDNA v Colonoscopy NNTT (find 1 CRC): FIT 208 sDNA 166 Colonoscopy 154

Ideal test for patients fearful of colonoscopy! Stool DNA Testing “Patients with a negative Gologuard test result should be advised to continue participating in a colorectal cancer screening program with another recommended screening method” Cologuard +ve ---> COLONOSCOPY Cologuard -ve ---> COLONOSCOPY Ideal test for patients fearful of colonoscopy!

CT Colonography Major Disadvantages: Nearly as sensitive as colonoscopy Still need bowel preparation Fecal tagging techniques being developed Need colonoscopy if positive Extracolonic findings can lead to futile work-up Major Disadvantages: Requires radiation for a screening test Not covered by insurance

Surveillance for Post Curative Surgery Colon Cancer 2012 USMSTF RECOMMENDATION: 1 year QUALITY of EVIDENCE: Moderate Colonoscopy 1 yr, 3 yrs, 5 yrs post surgery Rectal Cancer: EUS with Sigmoidoscopy 1 yr, 3 yrs, 5 yrs post surgery

Summary 10 yr colonoscopy 5 yr colonoscopy 3 yr colonoscopy NEGATIVE x2 (including distal HPs) Age 40-50 w NEGATIVE colon for other cause 5 yr colonoscopy NEGATIVE x1 NEGATIVE x2 w FDR age <60 1-2 small adenomas SSA/P < 10 mm w/o dyspl 3 yr colonoscopy 3-5 small adenomas HRAs (adenoma > 10mm, HGD, Villous features) SSA/P > 10 mm, SSA/P w dyspl, TSAs 1 yr colonoscopy > 5 small adenomas > 3 adenomas w > 1 @ 10 mm+ Malignant polyp < 1 yr colonoscopy Inadequate preparation Large flat adenomas w HGD Large flat adenoma or SSA/P w incomplete resection