Cancer-related complications such as anaemia, bowel obstruction,
and bowel perforation may also lead to symptom development.
Loss of appetite and loss of weight are symptoms suggestive
of advanced disease. Jaundice, cough, or breathlessness
raise the suspicion of distant organ involvement.
Diagnosis and Investigations
Diagnosis should be established only by tissue histology.
The primary site of cancer is generally the most accessible
site for biopsy through the colonoscope. Sometimes, in advanced
disease, biopsy specimens are obtained from an affected
lymph node or organ.
Chest radiography and computerised tomography (CT) of the
abdomen and pelvis are routine in the staging of colorectal
cancer. A bone scan and CT of the head are indicated when
symptoms or laboratory findings indicate that these areas
may be affected.
A raised serum concentration of carcinoembryonic antigen
(CEA) is helpful in the prediction and monitoring of disease
relapse or progression. However, the CEA is raised only
in some cases (60%), and it can be raised in non-neoplastic
disorders and with other cancers. Hence it should not be
used as a screening test. Its value in is in monitoring
for cancer recurrence when the initial tumour produced CEA.
Staging and prognosis
The 5-year survival rates for colorectal cancer by stage
of disease are as shown below:
| Stage
group |
TNM
criteria |
5-year
survival |
| Stage
0 |
Tis,
N0, M0 |
100% |
| Stage
I |
T1,
N0, M0
T2, N0, M0 |
90-100%
80-85% |
| Stage
II |
T3,
N0, M0
T4, N0, M0 |
55-70%
30-45% |
| Stage
III |
Any
T, N1-N2, M0 |
55-60% |
| Stage
IV |
Any
T, Any N, M1 |
<5% |
After resection the pathological stage is the single most
important prognostic factor. Other prognostic factors under
scrutiny are: tumour grade, perineural or lymphovascular
invasion, presurgical CEA level, presence of obstruction
or perforation, ploidy status, S-phase fraction, thymidylate
synthase expression, loss of heterozygosity of chromosome
18q, p53 mutation, and degree of microsatellite instability.
Surgery
Surgery is the mainstay of treatment for colorectal cancer.
It can be used for prevention, cure, and palliation.
Surgery is the only means of cure for localised colorectal
cancer. The precise operation depends on the location of
the tumour. For rectal cancer there is now a technique known
as total mesorectal excision. It has been reported to reduce
the rate of local recurrence.
Sometimes surgery is indicated in the treatment of advanced
cancer. It is done mainly to relieve symptoms or complications
caused by the cancer, such as obstruction and bleeding.
Occasionally, surgery can even be curative in selected cases
of metastatic cancer confined to the liver.
Chemotherapy
The three major forms are:
(1) adjuvant chemotherapy for curatively resected high-risk
stage II and stage III colorectal cancer,
(2) palliative chemotherapy for advanced colorectal cancer,
(3) neoadjuvant chemotherapy for non-resectable liver-only
metastases.
Despite curative surgery, a substantial number (40%) of
cases with stage III colon cancer will relapse. The addition
of adjuvant chemotherapy to surgery has been shown to decrease
relapse rates and mortality rates by 40% and 33%, respectively.
5-fluorouracil/leucovorin (5FU/LV) has remained unchanged
as the reference treatment since its introduction in the
late 1980s. Although different schedules are possible, one
widely used schedule consists of weekly intravenous doses
of 5FU/LV for 6-8 months. The benefits of adjuvant chemotherapy
are too small to justify its routine use in stage I/II colon
cancer. However, chemotherapy should still be considered
for stage II colon cancers when additional adverse prognostic
features are present.
Palliative chemotherapy has been shown to improve the quality
of life and lengthen survival in metastatic disease. For
the past four decades, 5FU/LV has remained the cornerstone
of treatment for advanced colorectal cancer. Treatment with
5FU/LV results in response rates of about 20% and median
overall survivals of about 12 months. The recent introduction
of two novel agents, irinotecan and oxaliplatin, has led
to the development of new and highly active regimens. Treatment
with irinotecan added to 5FU/LV (FOLFIRI regimen) as a first-line
therapy for metastatic colorectal cancer has produced superior
response rates (40-50%), delay in median time to progression
(7 months), and improvement in median overall survival (15-17
months).
In instances in which the liver is the only site of spread,
surgery represents the only chance of cure. Unfortunately,
most (70-80%) of these cases are unresectable. Some success
has been observed with neoadjuvant chemotherapy as an attempt
to make these cases to resectable ones by shrinking the
lesions.
Chemoradiation
5FU is a known radiosensitising agent and is sometimes
given concurrently with radiation therapy.
Local relapse after surgery is commoner after rectal than
after colon cancer. Hence postoperative radiation therapy
and chemotherapy given concurrently have become the standard
of care for stages II and III rectal cancer. This multi-modality
treatment improves local control and disease-free and overall
survival.
Chemoradiation has also been used to treat patients with
unresected locally advanced rectal cancer. Pre-operatively
chemoradiation aims to downstage the primary cancer sufficiently
for sphincter-sparing operations to be carried out. This
approach will help some of the patients to avoid an abdominoperineal
resection and colostomy.
Radiotherapy
Radiotherapy as a single modality of treatment has the
advantage of being able to provide local palliation without
systemic side-effects. Symptomatic bone and brain metastases
are two examples of conditions for which radiotherapy alone
may be desired.
Other Treatments
Investigations into the role of immunotherapies, angiogenesis
inhibitors, epidermal growth factor (EGFR) inhibitors and
cyclo-oxygenase II (COX-2) inhibitors in the treatment of
colorectal cancer are in progress. New promising data suggest
that cetuximab, an EGFR inhibitor, is active in refractory
advanced colorectal cancer when added to irinotecan. A recent
randomised study has demonstrated that a combination of
irinotecan and bevacizumab, an angiogenesis inhibitor, may
be beneficial in patients with untreated advanced colorectal
cancer.
Chemoprevention
Cohort studies suggest that calcium and folate supplementation
may prevent the development of colorectal cancer. Randomised
trials of the antioxidants beta-carotene and vitamins C
and E have not shown a protective effect.
NSAIDs and COX-2 inhibitors have been shown to reduce the
incidence of polyps in FAP. In fact, the US Food and Drug
Administration has approved the use of celecoxib (TM Celebrex)
for the chemoprevention of polyps in FAP. However, there
remains no direct evidence that the use of these agents
reduces the risk of colorectal cancer.
Dr
Donald Poon
Registrar
Medical
Oncology |
Dr
Simon Ong
Consultant
Medical Oncology
|
