Colorectal CancerWhen to refer ?

Dr Devinder Singh Bansi BM FRCP DM

Consultant Gastroenterologist

Imperial College

London

29.09.2011

2003 Estimated US Cancer Cases*

ONS=Other nervous system.*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Source: American Cancer Society, 2003.

Men675,300

Women658,800 210,816 Breast

79,056 Lung/bronchus

72,468 Colon & rectum

39,528 Uterine corpus

26,352 Ovary

26,352 Non-Hodgkin lymphoma

19,764 Melanoma of skin

19,764 Thyroid

13,176 Pancreas

13,176 Urinary bladder

62,238 All other sites

Prostate 222,849

Lung/bronchus 94,542

Colon/rectum 74,283

Urinary bladder 40,518

Melanoma of 27,012skin

Non-Hodgkin 27,012lymphoma

Kidney 20,259

Oral cavity 20,259

Leukemia 20,259

Pancreas 13,506

All other sites 114,801

Men675,300

Women658,800

2003 Estimated US Cancer Deaths*

ONS=Other nervous system.*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Source: American Cancer Society, 2003.

Men285,900

Women270,600

67,650 Lung/bronchus

40,590 Breast

29,766 Colon & rectum

16,236 Pancreas

13,530 Ovary

10,824 Non-Hodgkin lymphoma

10,824 Leukemia

8,118 Uterine corpus

5,412 Brain/ONS

5,412 Multiple myeloma

62,238 All other sites

Lung/bronchus 88,629

Prostate 28,590

Colon & rectum 28,590

Pancreas 14,295

Non-Hodgkin 11,436lymphoma

Leukemia 11,436

Esophagus 11,436

Liver/intrahepatic 8,577bile duct

Urinary bladder 8,577

Kidney 8,577

All other sites 62,898

Colorectal cancerSome useful statistics

• Approx 40,000 cases diagnosed in UK in 2008 (110 people/day)

• >80% in people aged 60 or over• Incidence relatively stable in last 10 years• 5 yr survival rates doubled in last 40 yrs

• STILL REMAINS 2nd most common cause of death from malignant disease in UK

Bowel cancer -UK

males females

New cases (2008) 22,097 17,894

Rate/100,00 pop. 58.5 37.8

5 yr survival (2001-6) 50% 51%

(colon cancer)

5 yr survival 92001-6) 51% 55%

(rectal cancer)

Colon Polyp

Colon Cancer

How Does Colorectal Cancer Develop?

Janne PA, Mayer RJ. N Engl J Med 2000;342:1960.

Colorectal cancer:At a local level

• Individual GP would expect to diagnose only 1-2 cases per year

• Bowel symptoms are common in the general population

• Increased number of ‘worried well’ patients • ‘well publicised large bowel cancer awareness campaigns

• How to select patients with large bowel symptoms who should be sent for urgent investigation ?

• A selection policy will inevitably lead to missed cases and potential litigation

Colorectal cancer:Symptoms may be site specific

• Rectal cancer• Classically tenesmus/rectal bleeding

• Sigmoid cancer• Altered bowel habit, with tendency to looser stool

• Right sided cancers• No or few GI symptoms• Palpable mass or anaemia

Colorectal cancer:Distribution of disease

• Rectum 27%• Rectosigmoid junction 7%• Sigmoid colon 20%• Descending Colon 3%• Splenic flexure 2%• Transverse Colon 5%• Hepatic Flexure 3%• Ascending Colon 7%• Caecum 14%• Appendix 1%• Other and unspecified 9%

Colorectal cancer:The significance of rectal bleeding

• Arguably the most diagnostically difficult symptom for GPs

• Common and, in isolation, only rarely caused by bowel cancer• Only 3% of 1000 pts with only rectal bleeding sent

to hospital for investigation

• Conversely, of all patients with left-sided CRC, approx. 60-70% report rectal bleeding as a principal symptom

Colorectal cancer:The significance of age

• Only 1% of all CRC occur in individuals <40 yrs

• 4% CRC occur in age range 40-50 yrs

• Risk rises more rapidly >50 yrs

• BUT

‘No one is too young to have bowel cancer’

Colorectal cancer:High Risk Individuals

• Anaemia or palpable mass (any age)• >50 yrs with CIBH >6 weeks to looser stool

and/or increased stool frequency• Rectal bleeding with CIBH (all ages)• >50 with rectal bleeding

• The danger of not investigating this group, even if it appears to be from benign ano-rectal causes, is that the patient may be falsely reassured and not represent when symptoms persist or change

• Patients of any age with symptoms and a strong FH of CRC

• Iron deficiency anaemia without an obvious cause (all ages)

Other symptomatic groups• <40 with symptoms of CIBH ?

• May be acceptable to adopt wait and see approach for 6 weeks as in most cases symptoms will be self-limiting

• However, important to have arrangements in place to review the patient and investigate if symptoms persist

• Patients with ‘bloody diarrhoea’ may have IBD so should be referred urgently

• <40 with symptoms of bright red bleeding but no CIBH ?

• Do not require urgent referral but a definitive diagnosis should be made

• Rectal examination/sigmoidoscopy as minimum. • Possibly watch and wait for 6 weeks but may be pressure to

refer to specialist

• If in doubt: REFER !

Referral of suspected Colorectal Cancer:Have guidelines made a difference ?

• British Journal of General Practice Aug 2004• Exeter Primary Care Trust

• All 361 cases of CRC (population 132000) from Jan 1998- Sept 2002 identified as part of a study examining GP records for pre-diagnostic clues to a malignant diagnosis

• 200 cases randomly selected

• 160 GP referral letters for suspected CRC available for study

Features of importance in CRC identified by GPs

• Rectal bleeding• CIBH (usually diarrhoea)• Weight loss• Iron deficiciency anaemia• Abdominal mass• History of IBD• History of colorectal polyps or signs of CRC on

previous investigation• FH of CRC• GPs opinion that patient has CRC• Mucus per rectum• Abdominal pain

Referrals made before and after the introduction of national cancer guidelines for CRC

June 1997-June 2000 June 2000-Sept 2002

n= 92 n=65

Mean age 69.8 69.3

Men 51(55%) 32 (49)

Patients referred urgently 38 (41) 32 (49)

Satisfied criteria for urgent

Referral 64/89 (72) 48/64 (75)

Satisfied criteria and had

Urgent referral 35/64 (55) 27/48 (56)

Did not satisfy criteria

And had urgent referral 2/25( 8) 5/16 (31)

Duke’s A or B cancer 49/87 (56) 31/50 (62)

Lessons ?

• Positive predictive value of symptomatic guidelines for diagnosing CRC is only 10%

• Significant number of patients diagnosed outside the ‘stream-lined’ referral route eg via A/E, other specialties

• Little increase in numbers of urgent referrals may represent the fact that many colorectal cancers do not meet the criteria for urgent referral.

• Urgent referrals outside the guidelines may be appropriate

• WHAT TO DO ?!

Referring Patients for Suspected Colorectal Cancer:Common reasons for litigation

• Failure to refer a patient with high-risk large bowel symptoms and so provide inappropriate reassurance

• Failure to do a rectal examination in a patient who subsequently proves to have a rectal cancer

• In the event that a practitioner has decided upon urgent referral to a specialist , a rectal examination is not necessary

• In the case of a ‘watch and see ‘ policy, better to do a rectal examination since the majority of expert witnesses tend to be of the ‘old school’ !!

• Defence based on ‘lack of causative consequences’• Demonstration of disseminated disease which would

therefore not effect prognosis

Survival by Dukes Stage

Symptoms of Colorectal Cancer

Time Course Symptoms Findings

Early None None

Occult blood in stool

Mid Rectal bleeding

Change in bowel habits

Rectal mass

Blood in stool

Late Fatigue

Anemia

Abdominal pain

Weight loss

Abdominal mass

Bowel obstruction

Staging of Colorectal Cancer

Frequency of Colorectal Cancer by Dukes Stage

Treatment of Colorectal Cancer by Stage

Is Colorectal Cancer Preventable?

YES!

• Screening

• Chemoprevention

Screening Techniques for Colorectal Cancer

Fecal occult blood test (FOBT) every year, or

Flexible sigmoidoscopy every 5 years,or

A fecal occult blood test every year plus flexible sigmoidoscopy every 5 years (recommended by the American Cancer Society), or

Colonoscopy every 10 years (recommended by the American College of Gastroenterology).

Screening For Colon Cancer SAVES LIVES!!!

MortalityTest Reduction

Fecal occult blood testing 33%

Flexible sigmoidoscopy 66%(in portion of colon examined)

FOBT + flexible sigmoidoscopy 43%(compared to sigmoidoscopy alone)

Colonoscopy ~76-90%(after initial screening and polypectomy)

Colorectal cancer screeningFirst assess RISK

AVERAGE RISK INDIVIDUAL• All patients age 50 years and older, the

asymptomatic general population

HIGH RISK• Personal history – polyp or cancer• Family history – polyp or cancer in first

degree relatives

Why aren’t more people screened for colon cancer?

Reasons for refusal of fecal occult blood testing• Fear of further testing and surgery • Feeling well • Unpleasantness of stool collection procedure

But:• Strongest predictor of whether a patient will be

screened = physician encouragement

Hynam et al. J Epidemiol Comm Health 1995;49:84Mandelson et al. Am J Prevent Med 2000;19:149

Fecal Occult Blood Testing

• Examination of stool for occult (“hidden”) blood

• Can detect one teaspoon or less of blood in a bowel movement

• Uses chemical reaction between blood and reagent

FOBT improves survival

Years after diagnosis

Trends in FOBT, 1997-2001

0

5

10

15

20

25

30

Total Men Women Less than HighSchool

High Schoolgraduate

Some collegeor greater

Prev

alenc

e (%) 1997

1999

2001

Source: Behavioral Risk Factor Surveillance System, 1996-1997, 1999, 2001, National Center for Chronic Disease

Prevention and Health Promotion, Centers for Disease Control and Prevention and Prevention, 1999, 2000, 2002.

Site Distribution

Flexible sigmoidoscopy• Pros

• May be done in office• Inexpensive, cost-effective• Reduces deaths from rectal cancer• Easier bowel preparation, usually done without

sedation• Cons

• Detects only half of polyps• Misses 40-50% of cancers located beyond the view

of the sigmoidoscope• Often limited by discomfort, poor bowel preparation

Selby et al N Engl J Med 1992; 336:653 Stewart et al Aust NZ J Surg 1999; 69:2Newcomb et al. JNCI 1992; 84:1572 Painter et al Endoscopy 1999; 3:269Rex et al. Gastrointest Endosc 1999; 99:727

Colonoscopy

• Pros• Examines entire colon• Removal of polyps performed at time of exam• Well-tolerated with sedation• Easier bowel preparation, usually done without

sedation• Cons

• Expensive• Risk of perforation, bleeding low but not negligible• Requires high level of training to perform• Miss rate of polyps < 1 cm ~25%, > 1 cm ~5%

Rex et al. Gastroenterology 1997; 112:24-8Postic et al. Am J Gastroenterol 2002; 97:3182-5

Chemopreventive agents

Fiber Not effective

Aspirin May be effective

NSAIDs (ibuprofen, etc) Probably effective

Vitamin E, vitamin C, beta carotene

Not effective

Folate Effective if obtained in diet

Calcium Effective

Estrogen Effective, but has other problems

Future techniques for colorectal cancer screening

• Stool DNA testing

• Capsule endoscopy (Givens capsule)

• CT colography (virtual colonoscopy)

Fecal Testing for Gene Mutations

Fecal Testing for Gene Mutations

• Pros• No sedation or preparation necessary• Home-based (sample mailed to physician)• No risk

• Cons• Current tests not very good (~50% of cancers

missed)• Cost• Frequency of exam unknown• Not therapeutic• Not covered by insurance

Videocapsule

Videocapsule

Lymphoma

CT Colography

Colon Polyp

CT Colography

Colon Polyp

CT Colography

Colon Cancer

CT Colography

• Pros• No sedation necessary• 20 min procedure vs. 25 min for colonoscopy• Low risk• Extracolonic lesions may be detected

• Cons• Preparation (residual fluid cannot be aspirated)• Air insufflation• Cost (? need for more frequent exams)• Radiation dose (similar to barium enema)• Not therapeutic• Not covered by insurance

Summary

• Colorectal cancer is the third most common cancer and cause of cancer death in the U.S.

• Chemopreventive agents have modest benefit in average risk individuals

• Screening for colorectal cancer saves lives!

• Patient and physician compliance with screening is poor