1. Brian Cox Research Associate Professor: Cancer epidemiology and screening University of Otago Hugh Adam Cancer Epidemiology Unit Department of Preventive and Social Medicine Dunedin School of Medicine

2. 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

3. 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.

4. Colonoscopy Flexible sigmoidoscopy. Aspirin - low dose. Possibly some other anti- inflammatory drugs. Calcium supplementation (1.2-2 grams per day).

5. Trends in colorectal cancer

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

8. 1940 Age group (years) Time Period 20-2425-2930-3435-3940-4445-4950-5455-5960-6465-6970-7475-7980-8485+ASR (20+) 1955-591.44.17.413.616.428.949.459.377.3102.0127.5167.2237.1193.737.9 1960-642.45.55.316.324.227.248.670.395.0111.7145.2167.1212.1230.441.6 1965-691.64.011.816.324.434.049.580.1111.8133.1160.0216.4236.9271.247.8 1970-741.74.910.518.528.547.865.393.7132.6170.1229.6271.1333.1377.360.8 1975-792.02.66.716.330.953.979.9111.3143.7172.9261.7304.4368.5471.167.1 1980-841.33.04.510.034.153.380.3117.7155.2213.4273.6353.6391.2449.871.0 1985-891.01.22.99.025.651.082.3124.1162.4217.5273.2357.6416.4511.071.6 1990-940.61.54.27.014.633.377.4132.1177.1222.2278.6349.0440.3500.370.2 1995-991.01.43.27.012.734.961.3124.8182.0240.9293.3367.1416.4433.569.3 2000-041.72.33.59.615.729.947.795.4176.0232.9323.3367.7433.6472.967.4 2005-090.43.16.49.016.826.744.978.2127.0226.3304.2368.5446.6445.162.3 1945

11. 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 None1221031 1-79967501.040.66, 1.67 800-119965590.810.51, 1.29 1200-1599891080.62*0.41, 0.93 1600-179962790.57*0.37, 0.90 1800 or more77960.62*0.41, 0.96 Test for trendP = 0.002

12. 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.

13. Randomised Controlled Trials 1.Hoff, G. et al. BMJ 2009 2.Atkin, W. et al. Lancet 2010 3.Segnan, N. et al. JNCI 2011 4.Shoen, RE. et al. NEJM 2013

14. Effect of a single screening test Detection rate (prevalence/incidence) Time

15. UK trial (Atkin et al 2010)

16. Time course of cases and deaths prevented 98/yr

17. 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

18. 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 screening test (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 work within 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 overseas initially 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.

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

20. FOBT Flex-sig Age range 50-7458-62 Frequency 2-yearlyonce Annual eligible pop 498,48548,664 Participation 50% Number screened annually 249,24324,332 Screens/wk 5,193507 Colonoscopies 12,4621,217 Endoscopies 025,549 Endoscopies/wk 260532 Prevented fraction if offered screening 2%21% Prevented fraction for distal cases 2%66% Annual cases preventedTotal CRC prevented 39422 % of all CRC cases 1%14.2% Prevented fraction for deaths 16%29% Annual deaths preventedTotal CRC 98179 % of all CRC deaths 8.1%13.9% Administrative cost per screen $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

21. 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.