Dr Alasdair PatrickGastroenterologist and

General Physician

Middlemore Hospital

Auckland

8:15 - 9:10 WS #194: Bowel Cancer

9:20 - 10:15 WS #206: Bowel Cancer (Repeated)

Dr Ben LawrenceMedical Oncologist

Auckland Hospital

Senior Clinical Research

Fellow

University of Auckland

Dr Nagham Al-

Mozany

Consultant Colorectal General SurgeonAuckland City Hospital Clinical Senior Lecturer University of Auckland

Bowel cancerMulti-discipline perspective

Dr Alasdair Patrick

Dr Nagham Al-Mozany

Dr Ben Lawrence

Overview

• Case history• Follow a patients battle with bowel cancer

– Risk factors for bowel cancer

– Options for screening• FOB, colonoscopy

• Bowel cancer screening program

– Symptoms & signs of bowel cancer

– Staging

– Treatment of bowel cancer depending on stage

Case History

• Mr FK

– 40 year old European man asks about screening for bowel cancer

– Fit and well

– No medications

– Smoker 10 per day for 10 years

– Family history

• Older sister had 3 polyps at colonoscopy aged 48

• Father died of bowel cancer aged 56

Presentation

Presentation

• Rectal bleeding + change in bowels in >55yo → more likely to be CR Ca

• Rectal bleeding + perianal Sx (itch / prolapse / pain) → more likely to be benign

New E-Referral PR Bleeding Pathway….

Coming to GP’s soon!

Developed by:• Dr. Nagham Al-Mozany, Colorectal and General Surgeon• Dr. Kathy McDonald, General Practioner & GP liaison Officer• Mr. Julian Hayes, Colorectal and General Surgeon

Auckland City Hospital

STAGING

• Staging is an estimate of the amount of penetration of a particular cancer

• It is performed for diagnostic and research purposes

STAGING

• Demonstrates metastatic disease

• Demonstrates local disease requiring pre-operative treatment– Rectal cancer

• Guides operative approach

• All cancer patients are discussed individually at a multidisciplinary team meeting

• Faster Cancer Track Pathway

STAGING

• Multiple systems for staging colorectal cancers depend on:

1. Extent of local invasion (T)

2. Degree of lymph node involvement (N)

3. Presence/Absence of distant metastasis (M)

• Definitive staging can only be done after surgery has been performed and pathology reports reviewed

Staging Adjuncts…Radiology

MRI Scan

CT scan(Chest, Abdomen, Pelvis)

STAGING SYSTEMSAJCC stage TNM stage

2002 6th edition TNM stage criteria for colorectal cancer (superseded by 2010 7th edition)[1][2]

Stage 0 Tis N0 M0Tis: Tumor confined to mucosa; cancer-in-situ

Stage I T1 N0 M0 T1: Tumor invades submucosa

Stage I T2 N0 M0T2: Tumor invades muscularispropria

Stage II-A T3 N0 M0T3: Tumor invades subserosa or beyond (without other organs involved)

Stage II-B T4 N0 M0T4: Tumor invades adjacent organs or perforates the visceral peritoneum

Stage III-A T1-2 N1 M0N1: Metastasis to 1 to 3 regional lymph nodes. T1 or T2.

Stage III-B T3-4 N1 M0N1: Metastasis to 1 to 3 regional lymph nodes. T3 or T4.

Stage III-C any T, N2 M0N2: Metastasis to 4 or more regional lymph nodes. Any T.

Stage IV any T, any N, M1M1: Distant metastases present. Any T, any N.

STAGING

• The broader stage of a cancer is usually quoted as a number I, II, III, IV derived from the TNM value grouped by prognosis; a higher number indicates a more advanced cancer and likely a worse outcome

Dr Alasdair PatrickGastroenterologist

Options for screening

• What is the aim?

– Cancer vs polyps

• Stool testing

– FOB

– iFOB

• Other technology

– CT colonography

• Colonoscopy

Cancer v polyps

• Bowel cancer: good candidate for screening as there is a treatable precursor lesion

There are different types of polyps

• Average risk asymptomatic adult

– 20-30% risk of polyps

• 1/3 of these have a polyp more than 10mm

• Two main types

– Serrated lesions

• New sub classification

– Adenomas

Serrated (saw tooth) lesions

• WHO classification (serrated lesions)

– Hyperplastic polyps

• 70-95%

– Sessile serrated polyps

– Traditional serrated adenoma

Hyperplastic polyps

• Identified 30 years ago

– Previously thought to have no malignant potential

• Now sub-classified

• Straight crypts

– Minimal distortion

– More serrated at top of crypt

– Common in left colon

Sessile serrated polyps

• Disorganised and distorted crypts

– Varying degrees of nuclear atypia

– Often find a mucus cap

– Mostly in right colon

• SSP/SSA are precursors of 1/3 CRC

– Autopsy studies find 25-50% prevalence

– More likely proximal and flat

– Account for disproportionate interval cancers

Adenomas

3 Histological types of adenoma

• A) Tubular adenoma

– Found in 30-50% of older adults

– Tumour cells form glands or gland like structures

• B) Tubulo-villous

– Mixture of villous and tubular morphology

– Increased malignant potential

Types of adenoma

• C) Villous adenoma

– Often larger

– Usually sessile

Risks of adenoma types

Cannot tell the type of adenoma on CTC-miss important prognostic information

Does size matter?

• Barium studies pre colonoscopy era

– Polyp > 1cm cancer risk

• 5 years 2.5%

• 10 years 8%

• 20 years 24%

– Flat or depressed lesions probably have higher risks (SSA)

What is the aim of screening?

• Detect only cancer

– FOB

– iFOB

• Detect cancer + polyps

– Colonoscopy

– Stool DNA

– CTC

– Colon capsule

• Detect and prevent cancer

– Colonoscopy

FOB testing

• The test card contains white paper impregnated with guaiac resin which turns blue in the presence of hemoglobin (after adding hydrogen peroxide, H2O2)

• The blue color results from oxidation of guaiac by H2O2 (the active ingredient in the developer fluid) in the presence of heme.

• The catalytic action of heme results from its peroxidase activity –animal heme in meat and plant peroxidases in certain foods also has peroxidase activity – which explains some of the false positive reactions that can occur.

• iFOB tests are more specific as they use antibodies to detect globin

Guaiac Resin

+Heme

+H2O2

Blue Color

Limitations of FOB

• A negative test result does not rule out intermittent bleeding or non-uniform distribution of blood in feces, and can result from high dose dietary or supplemental Vitamin C.

• A false positive result may be obtained on healthy persons due to dietary interferences (red meat), or medications (NSAIDs, corticosteroids, anticoagulants, cancer chemotherapeutics, and others).

• Does not detect polyps

11.6 x 31.5mm capsule with 172 degree image from each end

Adaptive frame rate 35/s-4/s

Clear liquid diet plus senna and 4L PEG plus boosts

Mixture of patients

88% egestion rate

Stool DNA

• Detect multiple individual DNA alterations

– APC

– KRAS

– P53

– BAT 26

• Still a work in progress

Role of CT colonography

• Positives for CTC– Is necessary in our endoscopist resource constrained environment

• Screening will add hugely to our waiting lists

– Great for incomplete colonoscopy• Technically challenging

• Obstructing lesions

– Great for the frail or co-morbid

– May increase participation in screening• Increased options for patient

My concerns regarding CTC

My concerns regarding CTC

• Small polyps can still be at increased risk of being advanced lesions

– In my experience CTC seems to underestimate polyp size

– We do not know about advanced pathology

– If we remove all polyps seen then costs and therefore benefits of CTC are greatly diminished as the initial test

• Incidental lesions

• Radiation risk

Do patients really prefer CTC?

– Bowel prep

– Rigid tube up the bum whilst awake!

Or do they prefer a pleasant, gentle and intimate

flexible camera insertion by a friendly Gastroenterologist?

Colonoscopy

• Remains the gold standard

• Finds cancer and polyps

• Removing polyps prevents future cancers

– Prevention is better than cure

National bowel cancer screening

Bowel cancer screening pilot

• Pilot using iFOB (OC-sensor, Eiken)

• Competitive RFP won by WDHB with support of ADHB and CMDHB

• WDHB residents

• 50 – 74 years of age

• Commenced October 17th 2011 until Dec 2015

• Two 2-year screening cycles

• Extended for another 2 years

Exclusion Criteria

• Colonoscopy in the last five years

• Previous colorectal cancer and/or in a

surveillance program

• Patients with UC or Crohn’s esp those

under surveillance

NZ bowel Screening Pilot

• Invite sent out on birthday

• Test kit –4 weeks later

• Results to GP/BSP (positive) – within 3 days

• Referrals for colonoscopy – within 10 days

• Colonoscopy – within 55 days

• Results (histology) to BSP within 10 days

• FSA if cancer within 10 days

• MDM within 20 days

Bowel Screening findings 2012-2015

•315 cancers in 303 patients•310 cancers/299 patients treated in public/private (8358 colos in 8187pts)

•43 cancers/39 patients treated in private

•171 males

•128 females

Bowel cancer screening

• Budget 2016

– $39.3 over 4 years for design, planning and set up

– Progressive roll out from mid 2017

• Narrowed criteria to 60-74 year olds

• 9 DHBs in 2018 and 8 in 2019

• There are significant resource issues– Each DHB could require 1 full time endoscopy theatre to meet demand

– 0.5 FTE surgeon also needed

Mr FK

• After a full discussion of his options

– Declined all screening

• 8 years later

– Develops PR bleeding

– Colonoscopy

• Find a large polyp

Stage 1 and 2: Gastroenterologist

• Three important considerations

– Ability to get a clear margin

– Lymphatic invasion

– Vascular invasion

• If any of these are compromised or the cancer is poorly differentiated then surgery is required

Ability to get a clear margin

• A pedunculated polyp containing a cancer can be snared off

• EMR

Ability to get a clear margin

• Endoscopic submucosal dissection (ESD)

Lymphatic and vascular invasion

• Lymphatic invasion– Looked for by pathologist

– Very few lymphatic's above the muscularis mucosa

• Vascular invasion– Looked for by pathologist

• Vascular markers may help – CD 31 and 34

Surgeon’s perspective

• All patients are discussed at MDT’s

Malignant Polyp or Early Ca

• Definition: Cancer invading into the submucosa

• Different classification systems:

1. Kikuchi (sessile polyps- sm1,2,3)

2. Haggitt (pedunculated polyps)

• Considered Early or T1

• Low risk- LN mets (<1%) EMR,TAMIS

• High risk-LN mets (>10%) needs surgery

Trans-anal minimally invasive surgery(TAMIS)- Novel techniques for early stage

cancers

Avoid Stomas?

Mr FK

• Missed repeat colonoscopy at 5 years

• Came back 9 years later

• Colonoscopy shows sigmoid tumour

– What next?

Surgical Options

Maximally invasive surgery Minimally invasive surgery

Complications

• Post-op mortality 2-5%

• Post-operative morbidity 30-40%– wound 10%

• wound dehiscence• wound infection• wound hematoma

– cardiorespiratory 10%– anastomotic dehiscence 5-15%– postoperative haemorrhage < 5%– stoma complications 10%– prolonged ileus 5%– urinary tract 10%– Sexual dysfunction varies 0-40 %

Mr FK

• Histology shows sigmoid adenocarcinoma

– T3 N1 M0

• Mismatch repair deficient

– B-Raf mutant

Stage 4 diffuse Stage 4 Oligo Stage 3

Oncology Perspective Stage 3 and 4

Adjuvant Chemotherapy

http://www.apple2.org.za/gswv/me/Boris/Genetech/Geneintro.html

Chemo destroys DNA so cancer cells can’t divide

Adjuvant Chemotherapy

ChemoP

ChemoL P

ChemoChemo L PL

ChemoChemo LP L

Mr FK

• 2 years later diffuse mets liver, lung, bone

ChemoP

Palliative therapy – not just chemo

Biomarkers determine choice

dMMRRas wtAny

Bevazicumab Cetuximab Pembrolizumab

Molecular therapies target growth pathways

Bevacizumab

Cetuximab

Checkpoint inhibitors show the cancer to the immune system

Pembrolizumab

Chemo 1 Chemo 2

Chemo 1 Chemo 2

Bevacizumab

Chemo 1 Chemo 2

Cetuximab Bevacizumab

Chemo 1 Chemo 2

Cetuximab Bevacizumab

Pembrolizumab

dMMRRas wt

Advances in median survival…

0 10 20 30 40 50 60

BSC

w CHEMO

w TARGET

w IMMUNE

Median Survival (months)

?

Mr FK

Chemo 1 Chemo 2

Cetuximab Bevacizumab

Pembrolizumab

Questions