Screening for Colorectal CancerA 21st Century Challenge

Thomas Weber MD FACSAssociate Professor of Surgery & Molecular

GeneticsAlbert Einstein College of Medicine

New York, New York

“Colorectal Cancer”An Ironic Tragedy in Three Acts

Act I

“A Nation Ravaged”

Act II

“Victory In Our Grasp”

Act III

“Paradise Lost”

Colorectal CancerAct I

“A Nation Ravaged”

• 148,000 cases anticipated for 2002*

• 55,000 deaths

• #1 solid tumor killer after lung cancer

• 10,400 cases in NYS

• 4000 deaths in NYS*ACS Cancer Statistics 2002

Colorectal CancerAct I

“A Nation Ravaged”

• An equal opportunity killer• Equal rates of death for women and men• 1 in 20 Americans affected• 1 in 10 with affected 1st degree relative

*ACS Cancer Statistics 2002

“A Nation Ravaged”

The Devil IS in the Details”

Colorectal Cancer Survival As A Function of Stage

at Diagnosis

NCDB Colon Cancer Survival

63% Stage III or IV55,000 Deaths

“A Nation Ravaged”The Devil IS in the Details

Distribution of Stage at Diagnosis

Only 37% of Colorectal Cancers are diagnosed while still localized

(node negative).

63% have regional or distant metastatic disease at the time of

diagnosis.

Colorectal CancerAct II

“Victory In Our Grasp”

• Screening for colorectal cancer removes pre-malignant lesions, promotes early stage diagnosis and saves lives.*

* Winawer et al. Gastroenterology 2003 124

* Selby et al. NEJM 1992 326:653-657

* Winawer et al. NEJM 1993 329:1977-81

* Newcomb et al. J Nat Can Inst 1992 84:1572-1575

Act II“Victory In Our Grasp”

• Colorectal Cancer and Breast Cancer

• Two VERY different paradigms

• Mammography is principally directed at earliest stage INVASIVE lesions (DCIS aside).

• Endoscopic Colorectal surveillance REMOVES PREMALIGNANT LESIONS.

Act II“Victory In Our Grasp”

• We have the tools!

• We have the case control and randomized evidence!

• Risk-benefit ratio is low!

• Cost is manageable!

• We have even achieved consensus!

An IRONIC Tragedy

Act III PARADISE LOST

Act IIIParadise Lost

• “Based on data from the Behavioral Risk

Factor Surveillance System fewer than one in five adults reported having had an FOBT in the previous year and only 9.5% of adults reported having had both an FOBT test and flexible sigmoidoscopy during an interval recommended by the ACS.”*

• *CDC Morb Mortal Weekly Rep 1999;48:116-121

Act IIIParadise Lost

• “Despite a consensus among expert groups on the effectiveness of screening for colorectal cancer, screening rates remain low.”*

* Winawer et al. Gastroenterology February 2003 124

Act ThreeParadise Lost

• “Evidence Demonstrates that when a screening recommendation comes directly from the clinician, compliance with colorectal cancer screening can be quite high.”*

*CA Cancer Journal 2001 51: pg 49

Act ThreeParadise Lost

• “Surveys of primary care providers and medical directors of managed care groups indicate a lack of preparedness to offer FOBT and flexible sigmoidoscopy”*

• “A recent report indicated medical directors were more likely to regard flexible sigmoidoscopy as an unreasonable expectation in a capitated plan“*

• “At this time economic and health care system disincentives to screening are impinging on CRC screeing efforts.*

*CA Cancer Journal 2001 51 38-75 CANCER

Act ThreeParadise Lost

A Summary of the Tragedy

“Improvement depends on changes in patients attitudes, physicians behaviors, insurance

coverage, and the surveillance and reminder systems necessary to support screening

programs”*

* Winawer et al. Gastroenterology February 2003 124

Epilogue

?

We Write The Epilogue

What Is The Current State-of-the-Art for Colorectal

Cancer Screening?

What is the best information that we have on this subject?

Key Elements In Screening Average Risk Individuals*

Consensus on the First Step

• “Screening programs should begin by classifying the individual patient’s level of risk based on personal, family and medical history, which will determine the appropriate approach to screening that person”*

* Winawer et al. Gastroenterology February 2003 124

Key Elements In Screening Average Risk Individuals*

• Men & Women 50 Years and Older• Stratify be Risk• Provide Options• Positive Screen => COLONOSCOPY• Cancer Detected => Definitive Therapy • Surveillance post polypectomy or surgery

* Winawer et al. Gastroenterology February 2003 124

Why Is Risk Assessment So Important?

The Impact of Family History on Colorectal Cancer Risk

• General population 6% 1 in 16

• 1 first degree relative 2-3 X

• 2 first degree relatives 3-4 X

• 1st degree < 50 years 3-4 X

• Multiple 1st degree 50%*

* Relative risk

The First Step:Risk Assessment

Three Questions for Every Patient

• History of CRC or Adenomatous Polyp• Predisposing Illness? eg Ulcerative

Colitis• Family History: CRC or Polyps

How many?First degree?Age at diagnosis?

Application of Risk Stratification

Three Questions for Every Patient• History of CRC or Adenomatous Polyp• Predisposing Illness? Eg Ulcerative Colitis• Family History: CRC or Polyps

How many?

First degree?

Age at diagnosis?• Answer is “NO” = Average Risk

70-80% of Colorectal Cancer in the United States Occurs Among

Average Risk Individuals.

70-80% of Colorectal Cancer in the United States Occurs Among

Average Risk Individuals

• For up to 80% of the CRC deaths sustained every year there is NO known predisposition clue!

• Rigorous Systematic Screening Protocol is the ONLY way we will save lives

Outline

• Screening Recommendations and their scientific support for:

• Average Risk

• Increased Risk

• High Risk

Screening RecommendationsAverage Risk Population

• Begin at age 50 for women and men

• Yearly FOBT

• Flexible sigmoidoscopy 5 year interval

• FOBT yearly, Flex Sig every 5 years

• Colonoscopy very 10 years

• Double-contrast every 5 years

Why Is There a Range of Options?

• No single test is of unequivocal superiority.

• Choice increases the likelihood that screening will in fact occur.

Yearly FOBT:Guaiac based with diet restriction or immunochemical with no restriction

Rational and Evidence

• Testing of 2 samples from 3 consecutive stools has been shown in 3 randomized controlled trials to reduce the risk of death from CRC

• Repeated annual testing can detect as many as 92% of cancers

WARNING!

Only 1 in 3 individuals with a positive FOBT undergoes

colonoscopy!

Flexible Sigmoidoscopy Every 5 Years

Rational and Evidence

• 4 case-controlled studies have reported reduced CRC mortality using flexible sigmoidoscopy.

• In the strongest study this reduction was 2/3rds for lesions within reach of the exam.

Warning!

• There was no reduction in risk for lesions beyond the reach of the flex scope.

• 50 % of patients with advanced proximal colonic cancers had NO distal (within flex sig range) colonic neoplasms.

Combined FOBT (yearly) and Flexible Sigmoidoscopy (5yrs)

• The effectiveness of the combination strategy has never been tested directly in a randomized trial.

• FOBT should be done first to minimize risks associated with multiple invasive procedures.

Colonoscopy every 10 Years

Rational and Evidence

• Several lines of evidence support screening colonoscopy.

• Colonoscopy integral part of the FOBT trials that demonstrated a reduction in CRC mortality.

• Colonoscopy is diagnostic AND therapeutic.

Colonoscopy every 10 Years

Rational and Evidence• There are no randomized controlled studies

evaluating whether colonoscopy alone reduces CRC mortality among individuals at average risk.

HOWEVER• 50 % of patients with advanced proximal

colonic cancers had NO distal (within flex sig range) colonic neoplasms.

Double Contrast Barium EnemaEvery 5 Years

Rational and Evidence

• There are no randomized controlled trials evaluating the impact of DCBE on CRC mortality.

• DCBE sensitivity is significantly less than colonoscopy

• DCBE has no therapeutic option

Outline

• Screening Recommendations and their scientific support for:

• Average Risk

• Increased Risk

• High Risk

CRC Screening for Individuals at Increased Risk

• People with a first-degree relative with colon cancer or adenomatous polyps diagnosed < 60 years or 2 first degree relatives at any age should be advised to have screening colonoscopy at age 40 or 10 years earlier than the first CRC diagnosis, and repeat every 5 years.

CRC Screening for Individuals at Increased Risk

• People with a first-degree relative with colon cancer or adenomatous polyps diagnosed > 60 years or 2 second degree relatives at any age should be advised to utilize same options as for average risk but begin at age 40.

CRC Screening for Individuals at Increased Risk

Rational and Evidence

• Screening recommendations for increased risk individuals are based on the known effectiveness of available screening procedures and the observed increased risk among affected relatives.

Outline

• Screening Recommendations and their scientific support for:

• Average Risk

• Increased Risk

• High Risk

High Risk:Familial Adenomatous Polyposis:

FAP

• 100% CRC cancer risk.

• Flexible sigmoidoscopy at age 10-12.

• Genetic counseling & testing.

• Prophylactic surgery performed by an experienced provider team.

High RiskHereditary Non-polyposis Colorectal

Cancer: HNPCC

• Colonoscopy every 1-2 years, beginning at age 20-25 years or 10 years younger than the earliest case in the family, whichever comes first.

• Supported by trials from the Netherlands and Finland by Vasen and Jarvinin respectively (Gastroenterology 2000; 118:829-834).

What Now?

Act IIIParadise Lost

• “Despite a consensus among expert groups on the effectiveness of screening for colorectal cancer, screening rates remain low.”*

* Winawer et al. Gastroenterology February 2003 124

Elements Required for Improvement*

• Patient attitudes

• Physician behavior

• Insurance coverage

• Surveillance and Reminder systems

* Winawer et al. Gastroenterolgy 2003 124 #2

Our Approach

“Partners in Prevention”

Partners in Preventionof Colorectal Cancer

• Taking the initiative in mobilizing all of the components required for success.

• Patients

• Physicians

• Support systems

• Research

Partners in Preventionof Colorectal Cancer

• Taking the initiative in mobilizing all of the components required for success.

• Patients > Risk Assessment

• Physicians > Guideline Clarification

• Support > Reminders

• Research > NIH & ACS

Partners in PreventionStrategy

1. Risk Assessment

2. Appropriate Screening

3. Follow-up & Reminders

Partners in PreventionStrategy

• General population outreach: AdvertisingEvents

• Advocacy groups• Academic medical & provider groups• Insurers• Employers• Trade Unions

Patient & Provider Priority Number One:Risk Assessment

Early Age Risk Assessment

Average Risk Increased Risk High Risk

How Does The Registry Work?

• We assess personal and family history of colorectal cancer AND adenomatous polyps

• RISK Assessment (ACS Guidelines)

• Screening & Recommendations

• Identify PROVIDER

• Access to research protocols

Familial CRC RegistryObjectives

• Public Health

Secure higher rates of screening

Especially increased risk groups

• Population Genomics

Study populations for the next generation of studies.

Registry Population Accrual Strategy

• Medical record retrospective review• Prospective

Surgical Admissions, Clinics, Admitting

etc• “Partners in Prevention”

Employee Health

Trade Unions

Faith Based Organizations

The Future?

Identifying Who is at RiskAmong the Negative History

Population?

• Selected Genetic Polymorphisms

• Predisposition Haplotypes & SNPS

• Novel gene discovery

Partners is looking for Partners!

• NYS & NYC DOH

• NYC H&H

• Insurers

• Employee Health

• Trade Union

Summary

• Colorectal Cancer remains a major public health challenge.

• We write the epilogue.

• Insurance industry support is crucial.

• Partners in Prevention is part of the solution.

Thank You!