Medical Articles

Colon Carcinoma

---

Overview

• Etiology – A brief summary
• Screening - Consensus
• Improvements in management:
  • Surgical
    • Locoregional Disease
    • Metastatic Disease
  • Systemic
    • Chemotherapy
    • Biologicals

Etiology

• Environment
• Genetics

Diet and Colorectal Cancer

The typical western diet creates a risk of colon cancer that is 10 times that of Asian diets. (Slatterly, 2000)

Meat

• Alters nutrient mix in the colon
• Changed Colonic Bacteria
• Heterocyclic Amines induce DNA mutation Study of 88 000 women comparing diets and colon cancer incidence (Willet WC, Stamfer MJ)
• Study of 50 000 men comparing diets and colon cancer incidence (Giovannucci E, Rimm EB et al)

Gut Bacteria

• Healthy bacteria produce substances that protect against colon cancer (short chain fatty acids such as acetic, proprionic and butyric acids)
• Harmful bacteria accumulate with overconsumption of animal meat and the decay that ensues leads to DNA mutation.

Sugar

• Studies have linked the consumption of simple carbs in the form of refined sugar and refined grains to an increased risk of colon cancer (Hill MJ)
• Excessive sugar consumption leads to insulin dysregulation, which has been shown to enhance cancer cell growth. Morbid obesity gives an all cancers increased risk of 2-3x

Chemicals

• Most damage from chemical exposure occurs via damage to DNA
• A study conducted by the National Cancer Institute found that farmers exposed to herbicides had a risk of cancer (all types) that is 6 times that of non farmers
• Tobacco smoking increases risk x3

Relative risk of colon cancer by leisure-time physical activity

Martínez et al J Natl Cancer Inst 1997;89:948

Energy balance, physical activity and risk of colon cancer in men

an Ounce of Prevention…
Varying levels of evidence

• Vegetarian Diets
• Fiber
• Fish Oil/Omega 3 Fatty acids
• Turmeric
• Folic acid
• Calcium/Vitamin D
• Antioxidants

Hereditary Colorectal Cancer Syndromes: HNPCC

• Hereditary non-polyposis colorectal cancer (HNPCC), sometimes called Lynch syndrome, accounts for approximately 5% to 10% of all colorectal cancer cases
• The risk of colorectal cancer in families with HNPCC is several times the risk of the general population
• People with HNPCC are diagnosed with colorectal cancer at an average age of 45
• Genetic testing for the most common HNPCC genes is available; measures can be taken to prevent development of colorectal cancer

Hereditary Colorectal Cancer Syndromes: FAP

• Familial adenomatous polyposis (FAP) accounts for 1% of colorectal cancer cases
• People with FAP typically develop hundreds to thousands of colon polyps initially benign but there is nearly a 100% chance that the polyps will develop into cancer if left untreated
• Colorectal cancer usually occurs by age 40 in people with FAP
• Mutations (changes) in the APC gene cause FAP; genetic testing is available
• Yearly screening for polyps is recommended starting in the late teens
• Attenuated familial adenomatous polyposis (AFAP) is related to FAP; people have fewer polyps

Screening

• Who to screen?
• When to screen?
• How to screen?
• Any proof that screening works?

CRC Incidence rate by age & sex

Who Is At Risk of Developing Colorectal Cancer?

• Men AND Women are at similar risk
• Risk increases with age
  • 90% occurs in people aged 50 +
• 85% of people with colorectal cancer had NO medical history related to colorectal cancer.

Screening is KEY!

• American Cancer Society estimates for the impact of colorectal cancer in 1999:
  • 129,400 cases diagnosed in the U.S.
  • 56,000 deaths in the U.S.
• At least 1/3 of deaths could be eliminated with widespread adoption of screening.

American Cancer Society recommendations for screening

• For adults aged 50+ with no family history of colon cancer or polyps:
  • Annual FOBT
    PLUS
  • Flexible sigmoidoscopy every 5 years
    - OR -
• Total colonic exam Colonoscopy every 10 years

Increased Risk Screening - Recommendations

• Family history of CRC: screening starts at age 40 or 10 years younger than family member with cancer
• Personal history of polyps/cancer: depends on history and histology
• Inflammatory bowel disease: surveillance starts after approximately 8 years of colonic disease

The screening tests

• Fecal Ocult Blood Test (FOBT)
• Flexible Sigmoidoscopy
• Colonoscopy (Gold standard)
• Double Contrast Barium Enema
• Virtual CT/MRI Colonoscopy

Virtual CT

Management

• Surgiicall
  • Locoregional
  • Metastases
• Systemic
  • Chemotherapy
  • Radiotherapy
  • Biologicals

Surgical Management Locoregional

• Aim Z– Remove tumour with adequate margins along with lymph node basin with minimal morbidity and mortality
• New and improved techniques
  • Minimal access surgery
  • Sphincter preservation (extremely low resection)
  • Total colectomy with ileoanal pouch
  • Transrectal surgery

Surgical Management Metastases

• Liver
  • Surgical resection remains the gold standard
  • Ablation with RFA
  • Chemoembolisation
• Lung
  • Surgical resection
  • RFA
• Combination

Resection

What is RFA?

Radiofrequency Ablation is a technique that uses high frequency alternating current to heat and thus destroy tissue.

An internally cooled needle is placed within the tumour and current is applied. Temperature, current and resistance are monitored in real time. An ablation takes 12 minutes and a spherical lesion of 3cm diameter is formed

Systemic Management Chemotherapy

Widely accepted

Improved survival!

What can be achieved?
Systemic therapy for stage 4 disease

What is available?

Oncology - Their language

Is it worth it?

Consensus – Adjuvant therapy

The new kids on the block!

How they work

The data

Progression free survival

Standard of care?

Neoadjuvant Therapy

But at what cost?

Cost of treatment for metastatic colon cancer

Phase III trial of bevacizumab in metastatic colon cancer

Cost-effectiveness of adding bevacizumab (Avastin) to chemo in metastatic colon cancer

• Randomized trial compared chemotherapy alone vs. chemotherapy + bevacizumab
• Bevacizumab regimen prolonged median survival from 15.6 to 20.3 months (p<0.001)
• Cost of extra 4.7 months?
  • $101,500 (assuming $5,000 per month for bevacizumab)
  • $259,149 per year of life gained (not quality adjusted)