Young onset CRC worldwideis this a new trend? Moe Htet KYAW Research Assistant Professor The Chinese University of Hong Kong

Young onset CRC worldwideis this a new trend? Moe Htet KYAW Research Assistant Professor The Chinese University of Hong Kong

A new/real trend in young-onset CRC? A separate amenity to older-onset CRC? Any measures we should take right now?

Heightened interest on young-onset CRC 40 Number of publications 35 30 25 20 Number of publications 15 10 5 0

Institution studies worldwide young-onset CRC Publication date Country Author % of Y-CRC over all Definition of Y-CRC CRC 2002 Nepal Singh 28.6% (26/91) Age <40 2003 Taiwan Chaing 6.7%(368/5436) Age< 40 2008 Italy Torsella 4.2% (58/1340) Age <40 2009 Singapore Chew 14% (523/3,796) Age <50 2009 India Nath 35.5% (102/287) Age <40 2010 India Gupta 39% (119/305) Age <40 2010 Finland Makela 4.6% (59/1272) Age <40 2011 Cambodia Hav 29.8% (103/356) Age<40 2012 Nepal Kansakar 28% (65/234) Age<40 2012 Vietnam Quach 28% (112/400) Age<40 2012 USA Chang 4.7% (55/1160) Age <40 2016 Korea Kim 9.5%(778/8207) Age<45

Proportion of hereditary cancer syndromes in young-onset CRC Year Author Country Study design Proportion of hereditary cancer syndromes (Lynch, FAP, HNPCC) 2010 Giraldez Spain Institution 14.3% (20/140) 2011 Limburg USA Institution 20% (39/195) 2012 Chang USA Institution 22% (16/75) 2015 Mork USA Institution 35% (67/193)

Population-based studies on young-onset CRC USA Publication date Country Author Period Source Study design Definition of Y-CRC Trend incidence Y-CRC Year commencing population screening 2003 US O connell 1973-1999 SEER Populationbased study 2006 US Cress 1992-2001 SEER Populationbased study 2009 US Siegal 1992-2005 SEER Populationbased study 2010 US Meyer 1973-2005 SEER Populationbased study 2015 US Bailey 1975-2010 SEER Populationbased study <40 Increase Opportunistic screening- <40 Increase in rectal cancer only <50 Increase <40 Increase in rectal cancer only <50 Increase 1987: 23% US population screened 2005: 50% population screened

Trend in colon cancer (1973-1999) USA, SEER 1973 Incidence Rate 1.8 per 100,000 1999 Incidence Rate 2.1 per 100,000 Young patients (Age 20-40) EAPC +0.75%, P<0.05 1973 Incidence Rate 179 per 100,000 1999 Incidence Rate 204 per 100,000 Older patients (Age >60) PAC +0.26%, P=NS O Connell, The American Surgeon, 2003

Trend in rectal cancer (1973-1999) USA, SEER Young adults (Age 20-40) 1973 Incidence Rate 0.8 per 100,000 1999 Incidence Rate 1.4 per 100,000 EAPC +3.15%, P<0.05 1973 Incidence Rate 80.6 per 100,000 1999 Incidence Rate 72.1 per 100,000 Older adults (Age >60) EAPC -0.73%, P<0.05 O Connell, The American Surgeon, 2003

Trend in young-onset CRC by ethnicity, Age 20-49 (1992-2005) USA, SEER M: APC +2.0% * F: APC +2.2%* M: APC -0.2% F: APC -0.5% Siegel, Cancer Epidemiol Biomarkers Prev, 2009 * P < 0.05

Highest trend in very young and rectal cancer (non-hispanic Whites) Age 20-29 M: APC + 5.2%* F: APC +5.6%* Rectum M: APC + 3.5%* F: APC + 2.9%* Siegel, 2009

Young-onset CRC by stage of presentation (1975 2010), USA, SEER Bailey, JAMA Surg, 2015

Increase incidence of young- onset rectosigmoid and rectal cancer in all cancer stages (1975 to 2010), USA, SEER Bailey, JAMA Surg, 2015

Predicted incidence rate of CRC by age compared with incidence rate in 2010 (USA) Colon cancer Rectosigmoid and rectal cancer Bailey, JAMA Surg, 2015

Limitations of SEER Program Represent 28% of country population No information on family history, related diagnosis (e.g. IBD, hereditary nonpolyposis colon cancer) Sporadic or hereditary cancer syndromes: what proportion?

Population-based studies young-onset CRC Rest of the World" Publication date Asia Country Author Period Source Study design Age Incidence Trend Y-CRC Year commencing population screening 2010 Hong Kong Yee 1983-2006 HK Cancer Registry Populationbased 2012 Korea Shin 1999-2009 Korean Central Populationbased Cancer Registry Australia, New Zealand <50 No increase 2016 <50 No increase compared to older age group 2004 2014 Australia (Victoria) 2015 Australia (South) 2016 Australia (NSW) Sia 2000-2010 Victorian Cancer Registry Young 1990-2010 Australian Institute of Health and Welfare Boyce 2001-2008 NSW Central Cancer Registry Populationbased Populationbased Populationbased <50 No increase 2006 <40 Increase 2006 <50 No increase 2006 2017 Australia (Western) Troeung 1982-2007 WA Cancer Registry Populationbased <50 Increase 2006 2017 New Zealand Europe Gandhi 1995-2012 New Zealand Cancer Registry Populationbased <50 Increase in rectal cancer N,A 2001 France Mitry 1976-1996 Burgundy cancer registry Populationbased <45 Increase 2008

Incidence rates per 10,000 and APC of CRC by site and age, Korean Central Cancer Registry, (1999-2009) Male Female Year commencing population screening = 2004 Shin, Cancer Res Treat, 2012 a p < 0.001

Highest APC in young men rectal cancer, Korean Central Cancer Registry (1999 2009) Male Female Year commencing population screening = 2004 Shin, Cancer Res Treat, 2012 a p < 0.001

Young-onset CRC: Population-based studies in Australasia

Increasing incidence young-onset CRC in Southern Australia and Western Australia Southern Australia (1990-2010) Western Australia (1982-2007) Young, Journal of Gastroenterology Hepatology, 2015 Troeung, Frontiers in Public Health, 2017

No increasing incidence of young-onset CRC in Victoria or New South Wales Victoria (2000-2010) New South Wales (2001-2008) Sia, Colorectal disease, 2014 Boyce, MJA, 2016

Real increasing trend in young-onset CRC or due to artifact of colonoscopy use?

We have seen.. Increasing incidence in older age due to shift in colonoscopy use (USA, SEER) 1984: Establishment of US Preventative Services Task Force 1987: NCI approved Working Guidelines for Early Cancer Detection https://seer.cancer.gov; accessed Aug 2017

Increasing use of colonoscopy in young adults ( age <50 years), USA, over 3 million colonoscopies MarketScan Commercial Claims and Encounters data (2001-20014) Increase use of colonoscopy parallel increase incidence of young CRC Murphy, Gastroenterology, 2017

True increase in incidence rather than artifact of more colonoscopy, USA 2004 Siegal, JAMA, 2017

Increasing trend young-onset CRC-mortality in Caucasian subjects, USA Siegal, JAMA, 2017

Is young-onset CRC separate entity to late-onset CRC? Consistency from institution studies: 1) Advanced stage at diagnosis 2) Location in the distal colon 3) Aggressive pathology features - poor differentiation, and mucinous and signet ring histology But Outcomes similar to late-onset CRC O Connell, Am.Surg, 2003 Taggarshe, Am.Surg, 2013 Dozois, Medicine (Baltimore), 2008 Chen, CGH 2016 Goldvaser, Int.J.Clin Oncol, 2011

Advanced-stage CRC in young not associated with longer duration of symptoms or time to diagnosis Chan, CGH, 2017

The big question Should we screen people earlier? Consider starting screening at age 40? Asia Pacific Consensus CRC screening recommends screening for regions with highest CRC incidence (>30 per 100,000 ) a Risk stratification- Tailored screening for young subjects with higher than average risk for CRC? a Sung, Gut 2015 https://seer.cancer.gov; accessed Aug 2017

DIRECTIONS FORWARD For future studies we need a consensus definition of young-onset CRC; it should be age < 50 without hereditary cancer syndromes as these should will not be offered screening Need more population-based studies Retrospective institution studies and potential referral bias Lack of numbers of young people with CRC -dispersal across the population and individual centers Studies of benefits of screening <50 years with CRC risk factors (smoking, DM, obesity) Increase awareness of young-onset CRC

Increase awareness of young-onset CRC Clinicians Proactively identifying young subjects with predisposing factors Not to ignore symptoms in young Timely follow-up of symptoms in young Patients Promote awareness in the young Young-onset CRC awareness campaigns

Summary Is this a new trend worldwide?... Yes.. in USA only Is it a separate amenity to older onset CRC?...Possibly.. but need larger and population based studies Any measures we should take?...increase awareness

.Just like for those over 50 years..ultimately. EARLY DETECTION and PREVENTION will determine the outcome of young-onset CRC Thank you for your attention