COLORECTAL CANCER
STEPHEN SMITH
GLOBAL BURDEN
THE DIET THEORY
• 95% Adenocarcinoma
• 1.4 million new cases CRC per year
• 2.4 million new cases by 2035
• 59% five year survival UK (2012)
• Approximately 47% preventable
• Third most common cancer worldwide
• Highest rates in Oceania and Europe
• Lowest in Africa and Asia
LOCAL IMPLICATIONS
• Commonest internal malignancy in Australia
• N=15,000 per year
• 1/10 chance in males to 85
• 1/15 chance in females to 85
• Age-standardized rate per 100.000
Australia no. 8 (38.4)
Korea no. 1 (45.0)
• 5 yr survival 66% (2006-10)
48% (1982-87)
RISK FACTORS
• AGE
• Genetics
• Diet: red meat, processed meat, alcohol
• Obesity, abdominal fat, height
• Smoking
• Conditions: colitis, FAP
• Exercise
• Diet: fibre, calcium (selenium, garlic)
FAMILY HISTORY
• No family history: 1/25
• 2nd degree relative: RR 1.5
• 1st degree relative >55 yo: RR 2
• 1st degree relative <55 yo: RR 5
• 2 x 1st degree relatives: RR 7
PATHOLOGY
• polyps • non polyp
• APC gene: polyps • HNPCC
• K-ras mutation: • MSI from mutations
oncogene in DNA mismatch
• p53 mutation: repair genes
apoptosis hMSH2, hMLH1,
hPMSI,hPMS2 and
hMSH6
GRADING AND STAGING
• Cuthbert Dukes (1890-1977)
Quaker, brothers (MI 6: Sir Paul
Dukes, Playwright: Ashley
Dukes)
OBE: services in WW1
1922: First pathologist at St
Marks
DUKES A,B,C
GRADING AND STAGING
• ACPS
A(1): In bowel wall
B(2): outer surface bowel wall
C(3): lymph nodes
D(4): metastatic disease
• TNM
T1-4: tumour depth in bowel wall
N0-2: lymph nodes (0,1-3,>3)
M0-1: metastases
SURVIVAL DATA
• Stage 1: 93% 5 yr survival
• Stage 2: 82%
• Stage 3: 59%
• Stage 4: 8%
CHANGING NATURE OF CANCER
INTERVENTION
• Retroactive
• Reactive
• Active
• Proactive
• Preactive
RETROACTIVE
• Metastatic symptoms:
• Weight loss
• Cachexia
• Anorexia
• Sweats / fevers
• Hamilton Bailey pictures
• Named syndromes and signs:
• Sister Mary Joseph Nodule
• Blumer’s shelf
REACTIVE
• Advanced cancer symptoms:
• Obstruction
• Tenesmus
• Abdominal pain and bloating
ACTIVE
• Subtle signs and symptoms
• Anaemia (fe deficiency)
• Change in bowel habit /consistency / colour
• Blood in bowel motion
PROACTIVE
• Surveillance vs screening
• FOB testing
• Flexible sigmoidoscopy screening
PREACTIVE
• Polypectomy
• Genetic testing
• (Prophylcatic colectomy)
• Aspirin
• Environmental manipulation
• Genetic manipulation
SCREENING
• FOB: RR 0.86 (95% CI 0.80 to 0.92) cancer mortality
• Flexible Sigmoidoscopy: RR 0.72 (95% CI 0.65 to 0.79)
cancer mortality
Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer
screening in asymptomatic individuals: Cochrane SR 2013
• (Colonoscopy)
NBCSP
• 50-75 yr olds (50,55,60,65,70,74)
• By 2020 all Australians aged 50 to 74 every 2 years
• 8% positive rate
• Adenoma rate 40%
• Advanced lesions 6-7%
• Cancers identified: 80% stage 1 and 2
• 5 yr survival projected approximately 80%
• 38% compliance
DIAGNOSTIC INVESTIGATIONS
• COLONOSCOPY
• CT Colonography
• (Barium Enema)
SURVEILLANCE (NHMRC)
• Personal cancer history: colonoscopy 3-5 yearly
• Polyps: colonoscopy 1-5 yearly
• Family history: strong, then from age 10 years
younger than affected 1st degree relative
• Gene positive: annually from 20’s
• FAP: annually from late teenage years
IMAGING MODALITIES
• CT chest/abdo/pelvis
• PET scan
• MRI pelvis
• ERUS
ENDORECTAL ULTRASOUND
• Mucosal surface
• Musc. Mucosa
• Submucosa
• Musc. Propria
• Serosal / fat
T1 invasion
Coeliac
Trunk:
Foregut
Superior
mesenteric Inferior
artery: mesenteric
Midgut artery:
Hindgut
ONCOLOGICAL SURGICAL PRINCIPLES
TREATMENT: CHEMOTHERAPY
• Node positive
• 5-FU (anti-metabolite)
• Leucovorin (folinic acid)
• Oxaliplatin (platinum, cytotoxic inhibition of DNA
synthesis)
• Capecitabine (metabolised to 5-FU)
TREATMENT: RADIOTHERAPY
• Neoadjuvant superior to adjuvant
• Rectal cancer to 12 cm
• T3
• N+ve
ENDORECTAL ULTRASOUND
• UT3N1 Lesion
• Serosal / fat
invasion
• T2 invasion
• Lymph node
involvement
MRI STAGING
ENDORECTAL ULTRASOUND
• UT4N1 Lesion
• Lymph node
• Sacrococcygeal
invasion
TREATMENT: METASTATIC
• Chemotherapy
• Bevacizumab (Avastin): angiogenesis inhibitor
• Surgery: liver/lung/peritonectomy
ADJUVANT THERAPIES
• Aspirin
• Exercise: Challenge study
• (Antioxidant treatment)
FOLLOW UP
• 5 year protocol
• Varies according to guidelines
• CEA (Carcino-embryonic antigen): 3 monthly for 2
years, 6 monthly for 3 years
• Liver scanning at 1-2 years for high risk (node
positive)