Colorectal Cancer

• Most bowel cancers are diagnosed in symptomatic patients
• 2nd most common cause of cancer death
• Australia has one of the highest rates of colorectal cancer globally.
• Colorectal cancer was the third most commonly diagnosed cancer in Australia in 2018.
• In 2022, an estimated 15,713 Australians were diagnosed with colorectal cancer, and 5,326 died from it.
• Screening with the immunochemical faecal occult blood test (iFOBT) is highly cost-effective.

Risk Factors

• Age >45 years (accounts for 90% of Colon Cancer)Inflammatory Bowel Disease
  • Ulcerative Colitis – Risk increases with duration since diagnosis (2% at 10 years of disease, 18% at 30 years of disease)Crohns Disease – Lifetime risk of Colorectal Cancer: 4-5%
  Adenomatous polyps >5mm (Confers RR of 2-3 times)Hamartomatous Polyposis syndromes

Family History (non-syndrome related)

• Higher risk Family History Criteria (RR 3-4x)
  • One first degree relative with Colorectal Cancer or advanced adenoma before age 60 years
  • Two first degree relatives with Colorectal Cancer or advanced adenoma at any age
• Moderate risk Family History Criteria (RR 2-3x)
  • One first degree relative with Colorectal Cancer or advanced adenoma age 60 years or older
  • Two second degree relatives with Colorectal Cancer or advanced adenoma at any age

Hereditary Syndromes

• Familial Adenomatous Polyposis (>100 synchronous advanced adenomas)
  • Diagnosed on average by age 39 years, and 87% develop Colon Cancer by age 45 years old
• Hereditary non-polyposis Colon Cancer (Lynch Syndrome)
  • Diagnosed on average by age 45 years, and 75-80% lifetime Colon Cancer risk
  • Autosomal dominant condition caused by germline mutations
  • Most common cause of inherited Colorectal Cancer
  • Surveillance colonoscopy every 1 to 2 years is recommended for individuals carrying a germline mutation
• Peutz-Jeghers Syndrome (Hamartomatous Polyposis)
  • Symptomatic polyps by age 10 to 30 years
• Sessile Serrated Adenomatous Polyposis
  • Diagnosed on average by age 62 years, and 25-70% have Colon Cancer at time of diagnosis

Lifestyle related risks

• Tobacco Abuse
  • Current smokers have a 2 fold higher Relative Risk of high-risk adenomas or Colorectal Cancer
• Obesity
  • BMI 35-40 associated with Colorectal Cancer mortality Relative Risk 1.8 in men, 1.4 in women
  • Bariatric Surgery reduced Colorectal Cancer rtisk by 27%

• Dietary Risk Factors
  • Dairy products have a minimal impact on Colorectal Cancer risk
  • Red Meat
    • Foods with possible higher risk: Salt-cured, pickled, smoked, barbeque
    • Red meat consumption does increase Colorectal Cancer risk

Spread

• Lymphatics – epigastric and para-aortic nodes
• Direct- peritoneum
• Blood – portal ciruclation

• Symptoms may depend on location
  • Right – anaemia, dyspepsia, mass
  • Left – pain, obstruction, altered bowel habit
  • Sigmoid – obstruction, altered bowel habit, rctal bleeding
  • Distal bowel/rectal – mass, rectal bleeding, tenesmus

History

• Often common , non specific symptoms with many causes- be suspicious if there is a combination of > 1 symptom or aged > 50
• Altered bowel habit
  • Frequency, consistency, calibre(narrowing)
  • Often increased frequency/loose stools if left sided
  • If change in bowel habit persists > 6 weeks – consider suspicious for malignancy/other pathology
• Rectal bleeding
  • More commonly intermixed
• Abdominal pain
• Anal pain and tenesmus
• Constitutional symptoms – weight loss, night sweats, fevers
• Symptoms of anaemia
  • Fatigue, dizziness, SOB, exercise intolerance, palpitations, apthous ulcers, angular chelitis, restless legs

• Explore family history
• Any other GI disorders

Examination

• Vitals, height, weight, BMI
• Signs of anaemia – pallor, tachycardia, heart murmur
• Palpate abdo – focal tenderness, masses, organomegaly
• Regional lymphadenopathy
• Perianal region – haemorrhoids or fissures to differentiate
• DRE – exclude rectal mass

Investigations

• Baseline bloods, inc iron studies
• If iron deficient – needs scopes
• If abdominal pain/mass – consider CT
• If there are red flags or > 1 colorectal symptom – refer for surgery or gastro assessment
• If identify benign pathology (e.g. Hemorrhoids) – manage accordingly and review at 6-8 weeks. If persistent or worsening symptoms refer
• CEA is not useful for diagnosis – may be for monitoring response to treatment

Management

• Early surgical excision
• Chemotherapy depending on prognosis

• Follow up generally includes
  • CEA antigen
  • Colonscopy
  • Abdominal imaing
• Avoid risks
  • Smoking
  • Low EtOH
  • Healthy BMI
  • Aspirin 100mg for 2.5 years between 50 – 50 years
  • Diet low in processed/red meat
  • High fibre

Bowel Cancer Screening

• CRC has pre cancerous stage as a polyp – 3 different pathways
  • Adenoma- carcinoma sequence (APC gene)
  • Serrated apthway (KRAS and BRAF)
  • Familial pathways – Lynch, familial adenomatous polyposis
• Screening aims to identify people harbouring a polup, and remove polyp or early cancer
• FOBT
  • Two forms
    • guiac
    • immunochemical
  • Immunochemical is used routinely
    • unlike guiac which is effected by diet, medications, red meat, vitamin C, anti-inflammatories
• If macroscopic loss or symptomatic- refer for colonoscopy – do not do FOBT

Population screening

• FOBT
  • In September 2023, the NHMRC endorsed updated guidelines recommending iFOBT screening to begin at age 45 for the general (average risk) population.
  • However, the NBCSP will continue sending iFOBT kits to individuals aged 50–74.
  • Every 2 years
• Colonscopy
  • for Category 2 & 3 (see below)
  • depsite this Despite this, colonoscopy use is common in high socioeconomic areas for Category 1.

Consider aspirin for prevention (fromhttps://app.magicapp.org/#/guideline/j1Q1Xj)

• for patients age 50- 70 years with Average or slightly increased
• age 45–74 years
• Dosage: A low dose of 100–300 mg per day is recommended for at least 2.5 years, starting between ages 50 to 70.
• Mixed evidence for chemoprevention: Trials for calcium, some vitamin supplementation, selenium, and statins have shown mixed benefits.
• Aspirin benefits:
  • Strong evidence from observational studies supports the benefit of nonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, in cancer prevention.
  • Reduces occurrence of CRC by 24%
• RCT results: Randomised controlled trials (RCTs) demonstrate aspirin’s effectiveness in the primary and secondary prevention of colorectal cancer and adenomas, comparable to colonoscopy screening in people under 70 years.
• Latency of benefits:
  • Cancer prevention benefits are seen only after 10 years of aspirin use, so patients should have a life expectancy of at least 10 years to consider its use.
• Personalisation of treatment:
  • The decision to take aspirin should be individualised, considering factors like age, sex, and potential reduction in cardiovascular events (e.g., thrombotic stroke and cerebrovascular events).
• Risk considerations: The individual must weigh potential risks such as
  • dyspepsia
  • peptic ulcer history
  • aspirin allergy
  • bleeding risk
  • renal impairment.
• Avoid aspirin in certain conditions:
  • Aspirin should be avoided in people with
    • active dyspepsia
    • history of peptic ulcer
    • bleeding diathesis
    • those at risk for gastrointestinal hemorrhage (e.g., those on anticoagulants or antiplatelets).
• Considerations for women over 65:
  • The benefit in colorectal cancer prevention is less certain for women over 65, but older women with cardiovascular risk factors may derive more overall benefit than harm based on available data.

Referral to Clinical Genetics Service or Familial Cancer Centre for Colorectal Cancer:

Personal History of Colorectal Cancer:

1. Isolated colorectal cancer diagnosed under age 50.
2. Personal history of colorectal cancer and a second Lynch syndrome–associated cancer (including two colorectal cancers).
3. Personal history of colorectal cancer and a family history of one or more first-degree or second-degree relatives with colorectal or endometrial cancer, with at least one cancer diagnosed under age 50.
4. Personal history of colorectal cancer and a family history of two or more first-degree or second-degree relatives with a Lynch syndrome–associated cancer, regardless of the age of cancer diagnosis.

Family History:

1. Family history of two or more first-degree or second-degree relatives with colorectal or endometrial cancer, with at least one cancer diagnosed under age 50.
2. Family history of three or more first-degree or second-degree relatives with a Lynch syndrome–related cancer, regardless of the age of cancer diagnosis.

Lynch Syndrome–Associated Cancers:

• Adenocarcinoma of the colorectum, endometrium, small intestine, stomach, ovary, or pancreas.
• Transitional cell carcinoma of the ureter or renal pelvis.
• Cholangiocarcinoma.
• Brain tumour.
• Sebaceous gland tumours.
• Keratoacanthoma.

from – Clinical practice guidelines for the prevention, early detection, and management of colorectal cancer: Population screening- Cancer Council Australia, 1.1 published on 22.11.2023 – https://app.magicapp.org/#/guideline/j1Q1Xj

Adults without symptoms
Risk level	Average
Definition	People with no symptoms (age 45–74 years)
According to family history
Risk level	Category 1: Average or slightly increased (age 45–74 years) (relative risk x 1–2)	Category 2: Moderately increased (relative risk x 3–6)	Category 3: Individuals at potentially higher risk, where Lynch syndrome has been excluded (relative risk x 7–10)
Definition	An individual should be advised that their risk of developing colorectal cancer is: — near-average risk if no family history of colorectal cancer — above average, but less than twice the average risk, if they have only ONE first-degree relative with colorectal cancer diagnosed at age ≥60 years.   This level of risk is still not high enough to justify colorectal cancer screening by colonoscopy.	An individual should be advised that their risk of developing colorectal cancer is at least two times higher than average,but could be up to four times higher than average, if they have any of the following: — only 1 first-degree relative with colorectal cancer diagnosed before age 60 years — 1 first-degree relative and one or more second-degree relatives with colorectal cancer diagnosed at any age — 2 first-degree relatives with colorectal cancer diagnosed at any age.   Include both sides of the family when assessing an individual’s risk category for colorectal cancer. Criteria for category 2 and category 3 can be met by inclusion of relatives from both sides of the family.	An individual should be advised that their risk of developing colorectal cancer is at least four times higher than average, but could be up to 20 times higher than average, if they have any of the following: — 2 first-degree relatives and one second-degree relative with colorectal cancer, with at least one diagnosed before age 50 years — 2 first-degree relatives and two or more second-degree relatives with colorectal cancer diagnosed at any age — 3 or more first-degree relatives with colorectal cancer diagnosed at any age.   Include both sides of the family when assessing an individual’s risk category for colorectal cancer. Criteria for category 2 and category 3 can be met by inclusion of relatives from both sides of the family.
Relative risk		At least two times higher than average, but could be up to four times higher than average.	At least four times higher than average, but could be up to 20 times higher than average.
Percentage of Australian population	98	1-2	<1
Lifetime risk to age 75 years (assuming no colorectal cancer screening)	Approximately 5–10%	Approximately 15–30%	Approximately 30–40%
Investigations:	iFOBT screening should be performed in line with population screening every two years from age 45 to age 74. low-dose (100 mg) aspirin daily should be considered from age 45 to 70 in consultation with a health care professional   Colonoscopy is generally not recommended for average or slightly increased risk individuals based on family history. Despite this, colonoscopy use is common in high socioeconomic areas. Colonoscopy carries direct and indirect harms, including: – Risk of death, occurring in approximately 1 in 10,000 to 14,000 procedures. – Harms from bowel preparation, such as dehydration and electrolyte imbalances. – Risks from sedation, including cardiovascular events. – Procedure-related risks, such as colonic perforation and bleeding.	colonoscopy should be offered every five years starting at 10 years younger than the earliest age of diagnosis of colorectal cancer in a first-degree relative or age 50, whichever is earlier, to age 74. CT colonography may be offered if clinically indicated. low-dose (100 mg) aspirin daily should be considered from age 45 to 70 in consultation with a health care professional. genetic testing is not indicated at present.	colonoscopy should be offered every five years starting at 10 years younger than the earliest age of diagnosis of colorectal cancer in a first-degree relative or age 40, whichever is earlier, to age 74. ·CT colonography may be offered if clinically indicated. low-dose (100 mg) aspirin daily should be considered from age 45 to 70 (see Aspirin) in consultation with a health professional. referral to a culturally safe family cancer clinic should be considered. Those carrying their family-specific mutation or having uncertain genetic status require careful cancer screening