Overview of colorectal cancer and its control in New Zealand

Brian CoxResearch Associate Professor: Cancer epidemiology and screening

University of OtagoHugh Adam Cancer Epidemiology Unit

Department of Preventive and Social MedicineDunedin School of Medicine

Problems with dietary studies

• Dietary data difficult to measure accurately in both case-control studies and cohort studies

• Dietary elements highly correlated

• Considerable diversity in study results

• Case-control studies seem to produce higher relative risks for associations between dietary elements and colorectal cancer than cohort studies or RCTs

• Vitamin supplementation

• Dietary intervention

Factors assessed and not consistently shown in RCTs to reduce risk of adenomas occurring and/or the

development of colorectal cancer.

• Colonoscopy

• Flexible sigmoidoscopy.

• Aspirin - low dose. Possibly some other anti-inflammatory drugs.

• Calcium supplementation (1.2-2 grams per day).

Factors shown in RCTs to reduce occurrence of adenomas and/or the development of colon or

rectal cancer

Trends in colorectal cancer

1955-59

1960-64

1965-69

1970-74

1975-79

1980-84

1985-89

1990-94

1995-99

2000-04

2005-09

0

10

20

30

40

50

60

70

80

Female colorectal cancer incidence

Time period

ASR 20+ (per 100,000)

HETEROGENEITY CHI-SQ (D.F.= 13) = 624.87 ( P <0.00005 )*******************************************************

Colonoscopy

1955-59

1960-64

1965-69

1970-74

1975-79

1980-84

1985-89

1990-94

1995-99

2000-04

2005-09

0

10

20

30

40

50

60

70

80

Female colorectal cancer incidence

Time period

ASR 20+ (per 100,000)

Female colorectal cancer incidence rates (per 100,000) - NZ

1940

             Age group (years)

 

           

Time Period

20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ ASR(20+)

1955-59 1.4 4.1 7.4 13.6 16.4 28.9 49.4 59.3 77.3 102.0 127.5 167.2 237.1 193.7 37.9

1960-64 2.4 5.5 5.3 16.3 24.2 27.2 48.6 70.3 95.0 111.7 145.2 167.1 212.1 230.4 41.6

1965-69 1.6 4.0 11.8 16.3 24.4 34.0 49.5 80.1 111.8 133.1 160.0 216.4 236.9 271.2 47.8

1970-74 1.7 4.9 10.5 18.5 28.5 47.8 65.3 93.7 132.6 170.1 229.6 271.1 333.1 377.3 60.8

1975-79 2.0 2.6 6.7 16.3 30.9 53.9 79.9 111.3 143.7 172.9 261.7 304.4 368.5 471.1 67.1

1980-84 1.3 3.0 4.5 10.0 34.1 53.3 80.3 117.7 155.2 213.4 273.6 353.6 391.2 449.8 71.0

1985-89 1.0 1.2 2.9 9.0 25.6 51.0 82.3 124.1 162.4 217.5 273.2 357.6 416.4 511.0 71.6

1990-94 0.6 1.5 4.2 7.0 14.6 33.3 77.4 132.1 177.1 222.2 278.6 349.0 440.3 500.3 70.2

1995-99 1.0 1.4 3.2 7.0 12.7 34.9 61.3 124.8 182.0 240.9 293.3 367.1 416.4 433.5 69.3

2000-04 1.7 2.3 3.5 9.6 15.7 29.9 47.7 95.4 176.0 232.9 323.3 367.7 433.6 472.9 67.4

2005-09 0.4 3.1 6.4 9.0 16.8 26.7 44.9 78.2 127.0 226.3 304.2 368.5 446.6 445.1 62.3

1945

Birth cohort (generation) risks of colorectal cancer in New Zealand

1906

1909

1912

1915

1918

1921

1924

1927

1930

1933

1936

1939

1942

1945

1948

1951

1954

1957

1960

1963

1966

1969

1972

0

0.2

0.4

0.6

0.8

1

1.2

1.4"Cohort effect for incidence"

"Cohort effect for mortality"

Year of Birth

Relative risk

Consumption of School Milk and Dairy Products, and Odds Ratios for Colorectal Cancer (Cox & Sneyd, Am J Epidemiology 2011)

* P < 0.05.** P < 0.01.a Adjusted by individual year of age, sex, ethnicity and family history of colorectal cancer in logistic regression.d Available for 482 cases and 495 controls.

Characteristic

Number of cases

Number of controls

Adjusted odds ratio for colorectal cancer a

95% CI

Total school bottles consumed d

None 122 103 1 1-799 67 50 1.04 0.66,

1.67 800-1199 65 59 0.81 0.51,

1.29 1200-1599 89 108 0.62* 0.41,

0.93 1600-1799 62 79 0.57* 0.37,

0.90 1800 or more

77 96 0.62* 0.41, 0.96

Test for trend

P = 0.002

Non-RCT evidence of effect • Very good evidence that FS is effective has been available for at

least 25 years.

• ~70-80% reduction in cancer of the sigmoid and rectum versus other sites from right-side versus left-side of colon and rectum seen in well-designed observational studies. The size of the reduction in incidence and mortality was so strong as to be very unlikely to be due to bias.

• The question for the last 25 years was, NOT does FS reduce cancer incidence and mortality, but by how much compared to FOBT and can it be delivered as a population-based programme.

• Since May 8, 2010, very good RCT evidence for FS screening has been available and supports the earlier well-designed studies.

Randomised Controlled Trials

1. Hoff, G. et al. BMJ 20092. Atkin, W. et al. Lancet 20103. Segnan, N. et al. JNCI 20114. Shoen, RE. et al. NEJM 2013

Effect of a single screening test

Detection rate (prevalence/incidence)

Time

UK trial (Atkin et al 2010)

Time course of cases and deaths prevented

0-4 years 5-9 years 10-14 years 15-19 years 20-24 years0

500

1000

1500

2000

2500FOBT deaths preventedFS deaths preventedFOBT cases preventedFS cases prevented

Years after starting

Number of cases/deaths prevented in each 5-year

period

39/yr

179/yr

422/yr

98/yr

Cost of waiting 3 years

At 15 years of follow-up

•1527 extra people will have developed colorectal cancer

•607 extra people will have died of colorectal cancer

•At a cost of $74m over 15 years

Advantages of flexible sigmoidoscopy

1. It visualises many abnormalities and allows biopsy at the same time as the test.

2. Treatment of polyps may be done for some people at the same time as the screeningtest (reducing losses to follow-up, especially important in hard-to-reach groups).

3. A one-off test is nowhere near as intense on invitation processes and follow-up (considerably reducing costs and losses to follow up).

4. GPs, nurses and medical technicians can be trained to do flexible sigmoidoscopy and workwithin an extended gastroenterology service.

5. Working with a gastroenterology service will make it easier for those GPs to maintain their acumen in gastroenterological disease in general.

6. Six-month training of a group of GPs or nurses would allow a programme to begin within 12 months. However, while a gastroenterologist or surgeon was training someone, they

would need a reduced case-load (about 15-20% lower). Bonded training overseasinitially could be arranged.

7. About 5% of screenees will need to come back for colonoscopy because high risk polyps were detected.

8. Given our higher incidence rate for bowel cancer than the UK, the invasive cancer prevention rate in New Zealand would be about 1 case for every 98 screening tests by FS between ages 55 and 64 years and 1 death prevented for every 170 screening tests.

Phased in national screening over 5 years – starting within 12 months

FOBT Flex-sigAge range 50-74 58-62

Frequency 2-yearly once

Annual eligible pop 498,485 48,664

Participation 50% 50%

Number screened annually 249,243 24,332

Screens/wk 5,193 507

Colonoscopies 12,462 1,217

Endoscopies 0 25,549

Endoscopies/wk 260 532

Prevented fraction if offered screening 2% 21%

Prevented fraction for distal cases 2% 66%

Annual cases prevented Total CRC prevented

39 422

% of all CRC cases 1% 14.2%

Prevented fraction for deaths 16% 29%

Annual deaths prevented

Total CRC98 179

% of all CRC deaths 8.1% 13.9%

Administrative cost per screen $5 $5

Savings in treatment and palliative care $4,867,800 $19,708,797

Administrative cost $1,246,213 $121,660

Saving minus administrative cost $3,621,588 $19,587,137

Workforce issues Flexible sigmoidoscopy can be provided by suitably trained GPs, nurses, or medical technicians within broadened gastroenterology services.

Training has been provided at the University of Hull in the UK since 1999. Other places also provide training.

The required increase in the number of colonoscopies would only be 2% of the current number performed for the first year, 4% in the second year, to 10% in the fifth year.

Therefore, the required increase in the number of gastroenterologists/colonoscopists would only be 2% for the first year, 4% in the second year, to 10% in the fifth year.

Need about 80 trained flexible sigmoidoscopists over 5 years (i.e., need to train about 16 a year for the first 5 years)

Facilities with support staff would need to be expanded.