cancer screening, DVT, TVE

1. Occult cancer screening
in
thromboembolic disease
Alexandru Andritoiu
Emergency Clinic Military Hospital Craiova
ROMANIA

2. CAT
(Cancer Associated Thrombosis)
• VTE is the second most prevalent cause
of death in cancer
• annual incidence of VTE in patients with
cancer is 0.5% compared to 0.1% in the
general population
• active cancer accounts for 20% of the
overall incidence of VTE

3. Relation TVE-Cancer (CAT)
TVE
TVE
TVE
months
Surgery
Radiotherapy
Chemotherapy
Catheters/portacaths
Hypercoagulable state

4. Armand Trousseau (1801-1867)
Lectures on Clinical Medicine
In lecture 95 “Phlegmasia Alba Dolens” Trousseau
discussed the relationship between unexplained
venous thromboembolism (VTE) and the subsequent
diagnosis of cancer and presented several cases to
illustrate this relationship.
“I have long been struck with the frequency with which cancerous patients
are affected with painful edema in the superior or inferior extremities”

5. Synchronous TVE-Cancer
Clinical case
• D. Elena, F, 62 yr
• RL-DVT (Fem-Pop)
• TE
• Gastric cancer

6. Upper arm DVT
Clinical case
N. Vasile, M, 72 yr
Pulmonary cancer (RSL)

7. TVE after surgery for cancer
Clinical case
V. Maria, F, 57 yr
Cerebral tumor operated
2 wks after surgery-DVT
RL-Fem-Pop

8. Thrombosis asociated
with portacath
Clinical case
R. Aurelia, F, 62 yr
• Acute leukemia
• Left Jug and subclav
vein thrombosis
(portacath)

9. Clinical case
S. Dorina, F, 59 yr
Unprovoked DVT-RL
(Fem-Pop)

10. Clinical case
A. Marius, M, 45 yr
• RL-DVT (Pop-V)
• Meniscectomy
• Provoked DVT

11. VTE Provoked vs Unprovoked
• The incidence of occult cancer in patients with
provoked VTE is significantly lower than in
patients with unprovoked VTE.
• Patients with surgery-related VTE appear to be
at particularly low risk of occult cancer
detection.
• The absolute rate of cancer between diagnosis
and up to 12–24 months of follow-up in patients
with provoked VTE seems to be < 2%
Monreal M, et al. Screening for occult cancer in patients with acute deep vein thrombosis or pulmonary embolism.
J Thromb Haemost 2004; 2: 876–81.

12. Tumors most strongly
associated with thrombosis
• mucin-producing cancers are the most often
associated with VTE-adenocarcinomas
• pancreas,
• lung,
• stomach,
• colon,
• breast,
• ovarian,
• prostate
• brain
• myeloproliferative disorders

13. The Cancer-Thrombosis
conection
Some cancers are more likely to be
prothrombotic:
• 27-28% in pancreas and lung,
• 13% in stomach,
• 3% in colon cancer.
Mirshahi S, et al. J Hematol Thrombo Dis 2015, 3:3

14. Prothrombotic properties
of tumor cells
Malignant cells can interact
with the hemostatic
system in multiple ways:
1) the capacity to produce and
release procoagulant and
fibrinolytic activities, as well as
inflammatory cytokines;
2) direct interaction with other blood
cells, i.e., endothelial cells,
platelets, and monocytes
Caine GJ et al. Neoplasia 2002 4, 465–473

15. Blom JW, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis.
JAMA 2005; 293: 715–722.

16. 4-10% in the first year
Acute VTE can be the first manifestation of an occult malignancy, and
patients presenting with idiopathic VTE are more likely to have underlying
cancer than those in whom a secondary cause of thrombosis is apparent
The risk of occult cancer detection in patients with unprovoked VTE
seems to be approximately 1 in 25 (recent data) not 1 in 10 (old data)

17. Screening for
occult cancer in DVE
Controversial (limited vs extensive)
• International guidelines recommend
that patients with idiopathic venous
thromboembolism should undergo
limited screening for malignancy, while
more extensive screening is reserved
for patients with abnormal findings in
the limited screening

18. Venous thromboembolism in adults:
diagnosis and management
(2012; revised in 2019)
Quality statement 5: Investigations for cancer
individuals older than 40 years presenting
with an apparently unprovoked venous
thromboembolism should have
investigations to exclude an occult cancer.
https://www.nice.org.uk

19. Strategies for limited vs extensive
occult cancer screening

20. Prognosis of patients with
Cancer and VTE
• Patients with cancer who develop VTE have
reduced life expectancy
• Those with cancer have a 4- to 8-fold higher
risk of dying after an acute thrombotic event
than patients without cancer
• The 1-year survival rate for patients with
thrombosis was 12% compared with 36% in
control patients.
• The mortality ratio associated with VTE was
2.2 for the 1-year follow-up period
Sørensen HT et al. Prognosis of cancers associated with venous thromboembolism
N Engl J Med. 2000;343:1846–1850.

21. RIETE prediction score
for occult cancer detection
after venous thromboembolism

22. Predictive score for estimating
cancer after TDE

23. • 854 people who had a new diagnosis of VTE
Carrier M, Lazo-Langner A, Shivakumar S, et al. Screening for occult cancer in unprovoked venous thromboembolism.
N Engl J Med. 2015;373:697-704.
33 patients (3.9%) were diagnosed with cancer at the time of screening,
14 (3.2%) in the standard screening group and 19 (4.5%) in the CT scan group.
After a negative screening result, the rates of cancer diagnosis in the
following 12 months were low:
1.18% for CT plus standard screening versus 0.93% for standard screening alone (NS).

24. The screening impact
• Occult cancer screening potentially has a large
economic cost, and may pose an important
significant psychological burden
• Trials comparing an extensive with a limited
screening strategy demonstrated that an
extensive screening strategy, including CT of
the abdomen and pelvis, was not cost-effective
• Aggressive cancer screening may lead to
unnecessary early anticoagulation withdrawal,
which can potentially lead to recurrent VTE
Coyle K, et al. Cost effectiveness of the addition of a comprehensive CT scan to the abdomen and pelvis for the detection
of cancer after unprovoked venous thromboembolism. Thromb Res 2017; 151: 67–71.

25. Conditions associated
with a higher risk for Cancer
Unusual sites:
• upper-extremity DVT represents 5–10% of all VTE
events
• splachnic vein thrombosis (30%)
• cerebral thrombosis (7.4%)
Thrombophlebitis migrans
Bilateral TVD
Recurrent unprovoked S/D-VT
Delluc A, et al. Occult cancer screening in patients with venous thromboembolism: guidance from the SSC of the ISTH.
J Thromb Haemost 2017; 15: 2076–9.

26. Age-specific and gender-specific
cancer screening
colon, breast, cervix, and prostate
should be performed according to
national recommendations
Delluc A, et al. Occult cancer screening in patients with venous thromboembolism: guidance from the SSC of the ISTH.
J Thromb Haemost 2017; 15: 2076–9.

27. Cancer screening in patients with a
recurrent unprovoked VTE
• 17% of patients with recurrent VTE also
had a newly diagnosed cancer within 2
years of follow-up, as compared with
only 4.5% of patients with no VTE
recurrence
• more extensive screening procedures
than those used for a patient with a
first unprovoked VTE.
Delluc A, et al. Occult cancer screening in patients with venous thromboembolism: guidance from the SSC of the ISTH.
J Thromb Haemost 2017; 15: 2076–9.

28. Earlier detection of cancer in pts. with
unprovoked TVE increase the survival
rate?
Can outcome be improved by earlier
diagnosis of occult cancers?
Not conclusive data!
Most probably NOT!

29. Clinical case
S. Dorina, F, 59 yr
Unprovoked DVT-RL
(Fem-Pop)

30. Which is the cause of DVT?
Can DVT be a sign of occult cancer?
Lab tests
• D-dimers (++)
• Dyslipidemia (Chol++/TG++)
• Type 2 DM
• glucoze 325 mg/dL
• ESR 4 mm/h
Extended blood test
• CEA
• CA15-3
• CA125
• CA19-9
Imaging
• Chest-Rx: normal
• Abd. US :normal
• Breast US: normal
• CT????-No!
• Follow-up! Yes!

31. Conclusions
• Unprovoked venous thromboembolism (VTE) can
be the first manifestation of cancer
• Recent studies report lower rates of cancer
compared to previous studies
• Ensure that patients are up to date with age-
and gender- specific cancer screening
• Extensive occult cancer screening should be
performed judiciously
• Current evidence does not support a net clinical
benefit to perform an extensive occult cancer
screening on all patients, and a decision to do
additional testing should be made on a case by
case basis.