Debate: General surveillance/screening for colon cancer in a resource constrained environment is imperative

Dr. Meryl OyomnoDepartment of surgery, University of Pretoria

INTRODUCTIONScreening is the systematic applicationof a test to identify

individuals at sufficient risk of a specific disorder (e.g. colorectal cancer CRC) to warrant further investigation or direct preventive action, amongst asymptomatic persons

associated with cure and improved survival

CRC screening testsAverage risk individual Fecal occult blood test FOBT (1yr) Fecal immunochemical test FIT (1yr) Multi-targeted stool DNA test (MT-sDNA)

(3yr) Flexible sigmoidoscopy FS (5yr) Colonoscopy (10yr) CT colonography (5yr) Capsule colonoscopy Septin 9 assay.

CRC Surveillance

Debate: General surveillance/screening for colon cancer in “a resource constrained environment” is imperative

Arguments against CRC screening1. CRC incidence2. Need for basic health care rather than preventative

measures3. Evidence for screening, how good is it? 4. False positives and negatives5. Complications6. Overall mortality7. Means and resources8. Poor attendance/ non-compliance9. Personal responsibility10. Socio-economic status SES11. Culture

1. CRC Incidence

Worldwide: 3rd most commonly diagnosed cancer.

UK: 2nd most common cancer after breast Ca. 3rd most common cancer after prostate and

lung

>36,000 new cases diagnosed each year

South Africa:

2. Need for basic health care rather than preventative measures Developed countries have already secured certain

standards of healthcare for the sick e.g. childhood vaccination, maternal health etc. and therefore screening can be next on the agenda

Developing countries this isn’t the case. There is a need to ensure equitable distribution of the little available resources.

Focus on the basics with the little resources available e.g. childhood vaccination, decreasing maternal obstetric and neonatal mortality, so as to achieve maximal impact and good for the larger population.

3. Evidence for screening, how good is it?Fecal occult blood test FOBT:

RCT showed a 15 - 33% decrease in mortality from CRC after 8 - 13 yr. follow-up period

With 5% lifetime risk of CRC and 50% mortality from the disease, the risk of dying from CRC is 2.5% without FOBT.. About 98% of us will die from something else. How do you sell these figures to doctors and the public?

Flexible sigmoidoscopy FS: A single FS screening between ages 55 and 64 years was associated with a

substantial reduction of CRC incidence and mortality. CRC incidence was reduced by 31% (RR = 0.69; 95% CI = 0.56 to 0.86) and mortality was reduced by 38% (RR = 0.62; 95% CI = 0.40 to 0.96) compared with the control group.

Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: no difference in diagnostic yield between the FS group and the FS plus FOBT group screening with regards to detection of CRC or high-risk adenomas

Norwegian RCT (1999-2001 & 15yrs follow-up)◦ Adults 54-64yrs at base line

◦ Screening FS vs. FS+FOBT◦ Norwegian Colorectal Cancer Prevention (NORCCAP) Trial

Measurements: Age-adjusted CRC incidence and mortality stratified by sex

RESULTS: 98,678 persons (20,552 screened, 78,126 no screening) Adherence: women 64.7%, men 61.4%

Absolute risks for death from CRC in women: 0.60% in the screening group and 0.59% in the control group (risk difference, 0.01 percentage point [CI, −0.16 to 0.18 percentage point];

HR, 1.01 [CI, 0.77 to 1.33]), in men were 0.49% and 0.81%, respectively (risk difference, −0.33 percentage point [CI, −0.49 to −0.16 percentage point]; HR, 0.63 [CI, 0.47 to 0.83]) (P for heterogeneity = 0.014).

CONCLUSION: Offering sigmoidoscopy screening in Norway reduced CRC incidence and mortality in men but had little or no effect in women.

4. False positives and negatives

FOBT (Haemoccult II)uses guaiac, a resin thatoxidizes and changes color in the presence of hemoglobin.

A poor test (30% specificity, 98% sensitivity) 2 – 17% positive predictive value (≈ 98% of patients with

a positive FOBT, have a normal colonoscopy)

Anxiety and psychological harm Wasted resources False sense of security Late diagnosis with poor outcome

5. ComplicationsScreening: “healthy”, asymptomatic individuals

NORCCAP Trial:6 perforations (1:336)

Rectal bleeding requiringadmission

Perforation rate of 1:769

Infection secondary to contaminated scopes Cardiovascular complications of mechanical bowel preparation and

sedation

Mortality rate: 1 in 16,745

6. Overall mortality

While screening decreases CRC inherent mortality, it does not decrease overall mortality.

7. Means and resourcesDo we have enough trained endoscopists? UK Only 17.0% of colonoscopists have received

supervised training for their first 100 colonoscopies and only 39.3% have attended a training course (Bowles et al. 2004)

2013: 1,289 trained medical gastroenterologists (Romaya C & Lockett M. 2013, GASTROENTEROLOGY WORKFORCE REPORT)

SA population of 57.7million

◦ 3.2 million persons over 64 years ◦ 36.9 million between 15 and 64 years old.

< 500 trained colonoscopists

Currently, we simply do not have enough trained endoscopists.

8. Poor attendance

Danish RCT: FOBT biennial screening ◦ The more screening rounds individuals are

enrolled into, the poorer the attendance.◦ lesser reduction in mortality from CRC.

Dropped from 18% to 11% after 5 screening rounds

9. Personal responsibility

Some may abandon healthy lifestyles if they believe that screening will pick up cancers at an early stage when it is more likely to be curable.

10. Socio-economic statusGap between the rich and poor

Canada (1997-2001) 1 664 188 people, 21.2% received a colorectal investigation Multivariate analysis: significant association between receipt of any

colorectal investigation and income (p < 0.001); People in the highest-income quintile had higher odds of receiving

any colorectal investigation (adjusted odds ratio [OR] 1.38; 95% confidence interval [CI] 1.36–1.40) and of receiving colonoscopy (adjusted OR 1.50; 95% CI 1.48–1.53).

These inequities persisted even after the launch of the programs to widely educate the public

Ontario Canada study (2005 – 2011) Immigrants and the poor are less likely to be screened for CRC Residents living in low-income neighborhoods were consistently

and significantly less likely to have a FOBT and be 'up-to-date' with CRC screening than long-term residents living in high-income neighborhoods (2.9-4.5%; 14.7-17.3% respectively).

11. Culture

Screening modalities should be culturally appropriate to the target population.

Public education

Summary The ideal screening method Money wasted on colonoscopy and consultation

fees following false positive screening tests.

A resource-constrained environment, Equitable distribution resources Wiser to spend this money on treating actual

patients with CRC rather than healthy members of the public.

First determine local data (incident rates, age etc.) ◦ CRC data base (screening, stage, surveillance)

◦ Finnish model

Ensure that there will be adequate numbers of trained endoscopists to carry out safe screening colonoscopy for those that will have positive screening tests

Screening should only be done if it is done in an organized fashion and linked to quality assurance programmes.

References1. Bernie, T., et al. (1998). "A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, hemoccult." BMJ 317(7158): 559-565.

2. Bowles, C., et al. (2004). "A prospective study of colonoscopy practice in the UK today: are we adequately prepared for national colorectal cancer screening tomorrow?" Gut 53(2): 277-283.

3. Force, U. P. T. (1996). Guide to clinical preventive services, Alexandria, VA: International Medical Publishing.

4. Gondal, G., et al. (2003). "The Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: baseline findings and implementations for clinical work-up in age groups 50-64 years." Scandinavian journal of gastroenterology 38(6): 635-642.

5. Hakama, M. (2002). "Cancer screening for medical oncologists: definitions and aims." Annals of oncology 13(suppl_4): 185-188.

6. Hardcastle, J. D., et al. (1996). "Randomised controlled trial of faecal-occult-blood screening for colorectal cancer." The Lancet348(9040): 1472-1477.

7. Hoff, G. and M. Bretthauer (2006). "The science and politics of colorectal cancer screening." PLoS medicine 3(1): e36.

8. Holme, Ø., et al. (2018). "Long-Term Effectiveness of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality in Women and Men: A Randomized Trial." Annals of internal medicine 168: 775-782.

9. Honein-AbouHaidar, G. N., et al. (2013). "Trends and inequities in colorectal cancer screening participation in Ontario, Canada, 2005–2011." Cancer Epidemiol 37(6): 946-956.

10. Kronborg, O., et al. (2004). "Randomized study of biennial screening with a faecal occult blood test: results after nine screening rounds." Scandinavian journal of gastroenterology 39(9): 846-851.

11. Ladouceur, R. and F. CCMF (2003). "Colon Cancer Screening." Presented at Débat: Contre Le Dépistage du Cancer du Colon.

12. Malila, N., et al. (2005). "Colorectal cancer screening in Finland: details of the national screening programme implemented in Autumn 2004." Journal of medical Screening 12(1): 28-32.

13. Mandel, J. S., et al. (1993). "Reducing mortality from colorectal cancer by screening for fecal occult blood." New England Journal of Medicine 328(19): 1365-1371.

14. Organization, W. H. (2002). National cancer control programmes: policies and managerial guidelines, World Health Organization.

15. Rex, D. K., et al. (2017). "Colorectal cancer screening: recommendations for physicians and patients from the US Multi-Society Task Force on Colorectal Cancer." The American journal of gastroenterology 112(7): 1016.

16. Samuels, S. (2014). Alex residents kill owls because they are used for ‘witchcraft’. Online: alexnews: online media journalism.

17. Segnan, N., et al. (2011). "Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial—SCORE." Journal of the National Cancer Institute 103(17): 1310-1322.

18. Singh, S. M., et al. (2004). "Association of socioeconomic status and receipt of colorectal cancer investigations: a population-based retrospective cohort study." Canadian Medical Association Journal 171(5): 461-465.

19. Solomon, M. J. and R. S. McLeod (1994). "Periodic health examination, 1994 update: 2. Screening strategies for colorectal cancer. Canadian Task Force on the Periodic Health Examination." CMAJ: Canadian Medical Association Journal 150(12): 1961.

20. Pillay-van Wyk, V et al, (2016). “Mortality trends and differentials in South Africa from 1997 to 2012: second National Burden of Disease Study.” The Lancet Global Health, 4(9):642-653.

Thank you