Colorectal Carcinoma- An Overview Dr C. L Chaw ST4, Clinical Oncology Tayside.

Colorectal Carcinoma- An Overview

Dr C. L Chaw

ST4, Clinical Oncology

Tayside

Colorectal Cancer (CRC)

3rd most common form of cancer and the 3rd leading cause of death in the Western World.

Annual incidence in UK -54/100 000, and 35000 new cases per year,>16000 deaths per year, making it the 2nd most common cause of cancer death in UK

Peak incidence ages: 60-70 yrs old ♂:♀ ratio for colonic and rectal cancer is 2:3 and 2:1 Colonic cancer ( 60%) is more common> than rectal

cancer (40%)

Risk Factors & Aetioloy

Environmental Factors Genetic

The aetiology is complex, involving interplay of environmental and genetic factors. These factors conspire to change the normal mucosa to a premalignant adenomatous polyp to a frank colorectal cancer over the course of many years

Environmental Factors

Diet Total calories – obesity and ↑ BMI (25-30kg/m2 )↑risk of CRC ↑ consumption of Meat (red meat) /Fat (saturated) /Protein - ↑ risk of

CRC High Fiber - ↓ risk of CRC Vegetables/ Fruits – Protective effects due to presence of antioxidants

Lifestyles Physical inactivity -↑ risk of CRC Cigarette smoking -↑ risk of CRC ↑ alcohol consumption -↑ risk of CRC

Genetics/Inherited predisposition

+ve family history of CRC, esp in 1st degree relative ≤ 40 yrs old --↑ risk of CRC

15% of CRC are familial in origins FAP (Familial Adenomatous Polyposis) HNPCC (Hereditary Nonpolyposis Colorectal

Cancer) /Lynch Syndrome

FAP Autosomal Dominant, mutation of APC gene

(5q21) 1% of all CRC Development of hundred to thousands of polyps in

patients in their teen-30s, almost 100% progress to CRC if not surgically resected

Extracolonic features: benign or malignant Benign:mandibular osteoma, epidermal cyst Gardner’s syndrome- desmoid tumour, osteoma and

adematous polyps Malignant: thyroid CA, brain tumours (Turcot’s

Syndrome), duodenal and ampullary CA.

HNPCC Autosomal Dominant, mutation of mismatch

repair genes – hMLH1,hMLH2, hMSH6, hPMS1 3% of all CRC Presence of up 100 colonic polyps ( hence

nonpolyposis), preferentially in right or proximal colon

Type I and Type II (distinguished by extracolonic tumours originating in stomach, small bowel, bile duct. Pelvis, ureter, uterus, bladder, ovary, skin)

Mean age of developing Ca ≈40 yrs old Lifetime risk of Ca in HNPCC is ≈80% for CRC, 40%

for endometrial Ca.

HNPCC (Amsterdam Criteria) Criteria 1:

≥ 3 family members with CRC, one of whom is 1st degree of the other 2

2 successive affected generations 1 or more cancer diagnosed < 50 years old FAP excluded

Criteria 2: ≥ 3 family members with HNPCC related cancer, one of whom is

the 1st degree of the other 2 2 successive affected generation 1 or more cancer diagnosed < 50yrs old FAP excluded

Lab testing of MSH 1&2 and PMS 1&2

Pathogenesis Vogelstein model Multistep to carcinoma formation

Mutation of APC gene –polyposis K-RAS (40-50%), P53, SMAD mutation DCC gene helps to initiate metastatic potential

Other pathway through MSI (DNA microsatellite instability) - HNPCC

Features of tumour

Spread

Adjacent organs – small/ large bowel, bladder, uterus

Transcoelomic spread- peritoneal disease Regional lymph node involvement ( 40-70%) at

presentation – usually follows the supplying blood vessels– pararectal, hypogastric, pre-sacral)

Haematogenous – liver ≥ lung ≥ bone and brain 25-30% patients at presentations, the tumour will

have spread either locally or distant sites, and will be unsuitable for radical treatment

Assessment & Management:

History Presenting complaints Family history Systemic enquiries

Physical examination (PR examination) Investigations Treatments

Signs & Symptoms

Symptoms Lower GI bleeding Altered bowel habits Abdominal pain Weight loss Loss of appetite Obstructive symptoms – vomiting, unable to pass

wind, severe abdo pain

Signs

Inspection: Jaundice, pallor , (freckles around the lip, buccal mucosal –Peutze Jeghers)

Palpable abdominal / rectal mass–don’t forget about the liver –hepatomegaly – distant mets

PR bleeding – fresh red ( left-sided colon/ rectum), malena (right-sided colon)

Alarming signs –Abdominal distension, peritonism, rebound tenderness, tingling bowel sound – bowel obstruction, perforation.

Pulmonary signs and neurological signs can sometime present if the disease is advanced.

Signs

Investigations

FBC ( Iron –deficiency anaemia ) U+E LFT ( metastatic disease ) CEA (carcinoembryonic antigen), is raised in

85% of patients with CRC, higher value associated with worse prognosis

Investigations

AXR ( if suspicious of SBO/ BO) Double contrast barium enema Colonoscopy with biopsy, Flexi/ rigid sigmodoscopy CT scan –Thorax, abdo USS liver - liver metastasis Pelvic MRI –particularly for rectal Ca – To asses

CRM (Circumferential resection margin) Endo-anal USS to asses nodal involvement in rectal

Ca

Investigations

Investigations

Investigations

Screening

50-75 years old FOB; higher false positive rate Colonoscopy; more specific and better at picking

proximal lesion.

Staging (TMN & Dukes )Dukes’Stage Description Stage

(AJCC)TNM

AIn situCancer confined to submucosa or

muscularis propria but not through it

0I

Tis N0M0

T1N0M0

T2N0M0

B(1) Into but not beyond muscularis propria;no LN spread

II T3N0M0

T4N0M0

B(2) Through the muscularis propria with no nodes involved

C(1) Nodes positive but not apical node III Any T, N1-2, M0

C(2) Apical node positive

D Metastatic IV Any T, Any N, M1

Prognosis ( 5-yr survival)

Stage I (Dukes A): 95% Stage II (Dukes B1/2): 70-80%

Stage III (Dukes C1/2): 40% Stage IV (Dukes D): 5%

Management

Radical/Curative Non-metastatic disease Multimodality approaches Surgery, chemotherapy, radiotherapy

Palliative Metastatic disease, inoperable disease Surgery, chemotherapy, radiotherapy Symptoms control

Management (Surgery- Curative)

Depending on site of lesions: Caecum, ascending colon, hepatic flexure – right

hemicolectomy Transverse colon – extended hemicolectomy Splenic flexure, descending colon –left hemicolectomy Sigmoid colon – high anterior resection Upper rectum- anterior resection

Defunctioning loop ileostomy is anastomosis <12cm from anal margin Lower rectum- Abdominal –perineal resection Total mesorectal resection- high rectum

Management (Chemothrapy)

Adjuvant Chemotherapy T3 disease or node positive tumours (Dukes C

disease, selective in Dukes B) – 4-13% survival benefits

Serosal involvement, perforated tumours, extramural vascular invasion or involvement of circumferential margin

5- Flourouracil based chemo, platinum based chemo

Side effects: nausea, myelosuppression, diarrhoea, neuropathy

Management ( Radiotherapy )

Rectal cancer – reduce rate of local recurrence, downstaging of inoperable disease

Pre-operatively or post-operatively 25Gy in 5#, 45Gy in 25# Side effects: erythema (local skin reaction),

cystitis, diarrhoea, sterility, urge incotinence, bowel dysfunction

Management ( Palliative )

Inoperable disease, medically unfit patients Defunctiong Colostomy, Surgical/ endoscopic

stenting – for obstructing lesions, aiming to improve quality of life

Resection for isolated liver and pulmonary metastasis if patients are fit.

Radiotherapy – palliation of local symtoms, bony pain, rectal bleeding

Management ( palliative )

Chemotherapy Patients selection- performance status 1-2 Aiming to improve quality of life and control of

disease Improves survival by 3-6 months 5-FU based chemo, platinum based.

References:

SIGN Guidelines no 67 Practical Clinical Oncology – Louise Hanna Cancer, Principle & Practice of Oncology –

DeVita, Hellman et al