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Colorectal cancer

Definition and classification

Cancer that develops in the colon and/or the rectum.

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Epidemiology

Third commonest cancer in the UK (after breast and lung)
40,000 people newly diagnosed each year
16,000 people died from bowel cancer each year

Incidence rate 50 per 100,000

The estimated lifetime risk of being diagnosed with bowel cancer is 1 in 15 (7%) for males, and 1 in 18 (6%) for females born after 1960 in the UK.

Incidence strongly increases with age, with trend starting at age 50y.
75% occur in people aged >65y; more common in men than women
Incidence higher in higher-income countries (Europe, North America, Oceania) and lowest in south and Central Asia and Africa.


Etiology

Genetic predisposition interacting with diet and lifestyle interventions.

Generic and molecular evidence to suggest most colorectal cancers develop over 10 years from colonic adenomas (polyps) that have acquired stepwise genetic mutations.

Benign colonic adenoma —-> Dysplastic pre-malignant colonic adenoma —-> Colonic cancer

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Risk factors (many of which are modifiable)

Age> 50y
Family history of colorectal cancer

Personal history of inflammatory bowel disease (UC, Crohn’s)
Smoking
Excessive alcohol
High consumption of red and processed meat
Obesity

Polyposis syndromes: Familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer (HPNCC, Lynch syndrome) are autosomal dominant inherited disorders that account for 3-5% of all colorectal cancers.


Pathology

Colorectal cancer is usually an adenocarcinoma.
Two-thirds located in colon, one-third in rectum.
Locally invasive, most common site for metastatic spread is the liver.


[Symptoms and Signs]


Diagnosis

Endoscopy (preferred if no major co-morbidities): Colonoscopy +/-biopsy
Alternatives (if major co-morbidities): flexible sigmoidoscopy +/-biopsy followed by barium enema or computed tomographic colonography (CT colonography).
However, if CT colonography identifies a lesion, histological biopsy by colonoscopy is required to confirm the diagnosis.

Other useful investigations:

  1. Blood: FBC to identify iron-deficiency anaemia

  2. Elevated pre-treatment serum levels of carcinoembryonic antigen (CEA) have:
    A negative prognostic significance
    No value in screening
    May predict relapse in patients after surgery suitable for further resection
    No usefulness for screening

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Staging

Colorectal cancer: contrast-enhanced CT of chest, abdomen and pelvis [+ contrast-enhanced MRI Brain if intracranial disease is suspected and/or PET-CT]


Rectal cancer: MRI +/- endorectal ultrasound (optimum modality to assess risk of local recurrence)

Tumour/node/metastases (TNM) classification:

TX: primary cannot be assessed
T0: no evidence of primary carcinoma in situ (Tis) - intraepithelial or lamina propria only.
T1: invades submucosa.
T2: invades muscularis propria.
T3: invades subserosa or non-peritonealised pericolic tissues.
T4: directly invades other tissues and/or penetrates visceral peritoneum.

NX: regional nodes cannot be assessed.
N0: no regional nodes involved.
N1: 1-3 regional nodes involved.
N2: 4 or more regional nodes involved.

MX: distant metastasis cannot be assessed.
M0: no distant metastasis.
M1: distant metastasis present (may be transcoelomic spread).

Staging

Stage 1
Stage 2
Stage 3
Stage 4

Primary tumour into, but not through, muscularis propria, and no metastases
Primary tumour grown through to serosa and peritoneal surface but no metastases
Any size of primary tumour with lymph node metastases
Presence of distant metastatic disease (e.g. liver metastases)


Principles of Therapy

  1. Treatment conducted by colorectal multidisciplinary team

  2. Treatment dependents on whether the tumour appears surgically resectable, its risk of local recurrence, the overall stage of the cancer, the general physical health (and co-morbidities) of the patient.
    Risk of local recurrence is determined by: anticipated/actual resection margin AND tumour and lymph node staging

Patient education

[Colorectal Surgeon]: Explain all treatment options, including no treatment, the potential risks and benefits, and the effect on bowel function.
[Stoma Nurse]: Explain the likelihood fo stoma, why it is necessary, and how long it may be needed


Surgery (and combinations)

Surgical resection of the tumour can be performed by laparoscopic or open surgery methods.
Surgery may be offered to attempt cure or relieve symptoms.

Types of surgery:
Total mesorectal excision: for rectal cancer
Right hemicolectomy: for tumours in the caecum, ascending and proximal transverse colon.
Left hemicolectomy: if in the distal transverse colon or descending colon.
Sigmoid colectomy: for tumours of the sigmoid colon.
Anterior resection: if in the low sigmoid or high rectum. Anastomosis is achieved at the first operation.
Abdomino-perineal (AP) resection: for tumours low in the rectum (less than approximately 8 cm from the anal canal). Permanent colostomy and removal of rectum and anus.
Resection of liver metastases (if resectable) or radiofrequency ablation of liver metastases (if patient is unfit)

Stage 1 rectal cancer, Stage 1 colon cancer
Tumours appear resectable with low risk of local recurrence
Offer further treatment if tumour resection margin was less than 1mm

Surgical resection

Rectal tumours appear resectable with moderate risk of local recurrence

Pre-operative radiotherapy + surgical resection

Operable rectal cancer at high risk of local recurrence, OR,
Locally advanced rectal cancer (borderline resectable) at high risk of local recurrence

Pre-operative chemoradiotherapy + Interval surgical resection
(interval allows tumour to shrink)

Stage 2 rectal cancer with high risk of recurrence, Stage 3 rectal cancer
Stage 2 colon cancer with high risk of recurrence, Stage 3 colon cancer

Surgical resection + adjuvant chemotherapy

Stage 4 colorectal cancer (metastatic disease)
Involve teams specialising in all relevant anatomical sites of the cancer (site specific MDTs such as specialist hepatobiliary MDT). Full discussion of treatment goals, risks and benefits with the patient

Provide symptom control and start chemo/radiotherapy
then interval surgical resection of primary and metastatic tumours


Chemotherapy and biological therapies

Following combinations are considered for patients with advanced and metastatic colorectal cancer:

  • FOLFOX (folinic acid plus fluorouracil plus oxaliplatin)

  • FOLFIRI (folinic acid plus fluorouracil plus irinotecan)

  • XELOX (capecitabine plus oxaliplatin)


Therapy (long-term): screening, safety netting and palliative care

6 week follow-up review after apparently curative resection

Regular surveillance for cancer recurrence:

  1. CT scans of the chest, abdomen, and pelvis (two CTs in 3 years)

  2. Serum carcinoembryonic antigen CEA tests (approximately 6 monthly)

  3. Surveillance colonoscopy (1yr post treatment, then 5 yearly thereafter)

Patient education:

Offer all patients specific verbal and written information on managing the effects of the treatment on their bowel function. This could include information on incontinence, diarrhoea, difficulty emptying their bowels, bloating, excess flatus, diet, and where to go for help in the event of symptoms (safety netting)

Referral to palliative care team

  1. Resection of metastatic disease (hepatic or pulmonary metastases)

  2. For patients with metastatic colorectal cancer, chemotherapy aims to improve survival and quality of life.

  3. About 15% of patients with liver metastases initially judged to be unresectable will become resectable after systemic chemotherapy, with improved long-term survival.


Complication: presentation with acute large bowel obstruction

Colorectal cancer may present as acute onset large bowel obstruction.

Symptoms and signs: abdominal pain, vomiting, abdominal distension

Need to resuscitate the patient

Undertake CT chest, abdomen, and pelvis to:

  • confirm the diagnosis of mechanical bowel obstruction

  • detect metastatic disease

  • detect colonic perforation.

Treatment options

  1. Immediate surgery (such as colectomy)

  2. Insert a self-expanding metallic stent and undertake interval surgery.
    Ideal option to manage left-sided complete/near complete colonic obstruction

However, do not place self-expanding metallic stents:

  • In low rectal lesions or

  • To relieve right sided colonic obstruction or

  • If there is clinical or radiological evidence of colonic perforation or peritonitis


Prognosis: morbidity and mortality

Colorectal cancer is the second most common cause of cancer death in the UK.

5-year survival depends on stage of cancer at treatment: Stage 1 (>90%) and Stage 4 (10%)

Overall, average 5-year survival 50%.


Prevention and Control

Preventive factors that reduce risk include: physical activity, hormone replacement therapy, and aspirin.

Screening programmes, using interval screening by sigmoidoscopy/colonoscopy, have been shown to reduce incidence and mortality from colorectal cancer. This is attributed to colonoscopic removal of ‘precancerous’ colonic polyps as well as enabling early detection of colorectal cancers.


Clinical prediction guides