Venous Thrombosis Linked to Some Cancers

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Screening for cancer in venous thromboembolic disease

The incidence is higher but intensive screening isn't

warranted

The association between cancer and venous thrombosis

has long been recognised. 1 2 Though venous thrombosis

is a well known complication of established cancer, it

might also be a marker of an otherwise occult cancer.

If so, this raises the issue of whether otherwise

healthy patients presenting with a venous

thromboembolic event should be investigated for a

possible underlying cancer on the grounds that a

cancer diagnosed early may be more amenable to cure.

Whether screening for an underlying cancer is a good

use of resources will depend on how common such

cancers are; the cost, accuracy, and acceptability of

the screening tests; and, most important, whether

early detection of such cancers would improve patient

outcome.

Large prospective studies of patients presenting with

venous thromboembolic disease, linking hospital

records with national cancer registers, find an

incidence of previously undiagnosed cancer of 4-6.5%,

giving standardised incidence ratios of 1.3-3.2.3-5

Smaller retrospective and prospective studies looking

particularly at patients with no obvious risk factors

for their thrombosis find higher incidences of cancer,

of 7.3-12% compared with 1.9-2.9% for patients with

risk factors.6-8 In these studies patients were not

specifically investigated for an underlying cancer,

the diagnosis being made after routine investigation

on admission or after 6-12 months' follow up. Two

studies in which patients underwent intensive

investigations for cancer at the time of presentation

found an incidence as high as 19% in patients with no

risk factors. 9 10

What investigations might prove useful as screening

tests for occult cancers? When routine investigations

were supplemented with abdominal and pelvic computed

tomography or ultrasound scanning and carcinoembryonic

antigen measurements in 424 patients with suspected

venous thrombosis 9 10 cancer was diagnosed in 33

patients (7.7%). In 21 cases the diagnosis was made on

the basis of history, examination, or routine tests,

but in the remaining 12 cases the diagnosis was made

only after scanning or a carcinoembryonic antigen

measurement, a detection rate of only 3.2%. This would

have been appreciably higher if only patients with no

risk factors had been so investigated.

In contrast, in a study of 136 patients with no risk

factors for thromboembolism cancer was diagnosed in 16

patients (12%), all of whom had at least one abnormal

finding on history, a thorough examination, full blood

count, or chest x ray examination.7 Only 56 patients

could have been classified as entirely normal, and in

these patients no cancers were found at the time of

presentation or on subsequent follow up. In this study

a potential 59% of patients would have required

further investigations for cancer, with at best a

detection rate of 20%. In a second study of 326

patients, 10 of 13 cancers were diagnosed on the basis

of an abnormal history, examination, full blood count,

liver function tests, or urea and electrolyte

measurements.8

Would early detection of these cancers improve patient

outcome? Possibly, if the patient has a carcinoma of

the breast, ovary, colon, or cervix, but there is no

evidence for improved outcomes in carcinomas of the

lung, brain, prostate, or pancreas, all of which have

been associated with venous thrombosis. Furthermore,

we cannot assume that these apparently occult cancers

are indeed at an early stage of their development

since they have already had a major clinical impact.

One study has recently reported on the survival of

patients who were diagnosed with cancer at or around

the time of presentation with a thromboembolic

event.11 When these patients were compared with age

matched controls, with similar cancers but without an

associated thrombosis, 44% were found to have

metastases at the time of diagnosis compared with 35%

of controls. One year survival was only 12% compared

with 36% in the controls. If the cancer was diagnosed

within 12 months of a thromboembolic event one year

survival was 38% compared with 47% in the controls.

The study concludes that patients with cancer

diagnosed at or around the time of a thromboembolic

event have a significantly worse prognosis than those

patients without such an association.

So would screening for cancer in patients who present

with a venous thromboembolic event be an effective use

of resources? In the absence of an obvious risk factor

for thrombosis there is a clear increase in the

incidence of an underlying carcinoma in these

patients. Estimates range from 7.3% to 19% at the time

of presentation. Assuming an incidence of perhaps

around 10%, screening for cancer becomes a reasonable

option. On the basis of current evidence, however,

intensive investigation cannot be recommended.

Firstly, cancers associated with venous thrombosis

seem to have a relatively poor prognosis, and early

diagnosis of many of these cancers has not been shown

to improve survival. Secondly, we should not

underestimate the potential harm to patients, both

psychological and physical, associated with any kind

of screening programme, as increasingly invasive

investigations may be used to follow up abnormal

screening tests for what may turn out to be benign or

untreatable disease.

A practical approach would be always to consider the

possibility of an underlying cancer in patients

presenting with a venous thrombosis, particularly if

they have no underlying risk factor for the

thrombosis. We should take a careful history and make

a thorough examination and do the simple routine blood

testsfull blood count, liver function tests, urea and

electrolytesand a chest radiograph. This simple screen

will lead us to the diagnosis in most patients with an

underlying cancer. Further investigations would depend

on the results of these tests. Before recommending

more intensive investigations we need the results of a

large randomised prospective study to assess whether

incorporating investigations such as tumour markers,

faecal occult blood, and computed tomography into a

screening protocol will lead to improved outcome for

those patients found to have an underlying cancer.

Tony Fennerty, consultant in general and respiratory

medicine.

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