Case 39 – summary

.The final part of our case was dedicated to discussing what tests, if any, should be requested on a patient presenting with an unprovoked VTE (uVTE). Clearly there are many other topics in the field of ‘clots and cancer’ that are worthy of examination (anticoagulating the cytopenic patient, anticoagulating the dying patient, management of incidental VTE on scans performed for staging cancer, the pathogenesis of cancer and thrombosis) but we can’t cover everything in one go – perhaps these topics may appear in future cases. The data most pertinent to this week’s discussion is summarised below. Please see  https://storify.com/TeamHaem/clots-and-cancer for the Storify summary of our debate.

What are the stats when it comes to clots and cancer?

  • One systematic review of 14 studies found cancer is present in 6% of patients presenting with VTE, rising to 10% at one year post VTE (Carrier et al 2013). This is similar to previous data.
  • Sorenson (1998) showed that in those patients with cancer, the onset of  overt cancer occurred within six months of presenting with a VTE.
  • Cancer is more likely to underlie a VTE presentation in young patients standardised incident ratio) – this is because VTE is more common with age for multiple non-malignant reasons (Sorenson 2000).
  • 40% have metastatic disease at presentation.
  • It is known that survival is poorer in cancer patients who present with VTE than those that don’t (independent of complications from the VTE or anticoagulation): 12% v 36% 1 year survival (Sorenson 2000).
  • Bilateral DVTs, very elevated D-Dimers and early recurrence of VTE (especially whilst on anticoagulation) are particularly strongly associated with cancer and the BCSH guideline (2015) recommends investigating these patients more extensively.

Why should the clinician who diagnoses uVTE look for cancer?

The desire to improve the cancer outcome is strong and is a major motivator for most doctors who see these patients. However the data on this is not encouraging–  see below.

Certainly the detection of a cancer will influence further management of the thrombosis however as it may:

    • Affect the choice of anticoagulant
    • Identify those at higher risk of bleeding, e.g. GI lesions.

Detecting cancer in these patients: which tests are helpful?

  • Routine tests (History, exam, FBC, biochemistry, ESR, urine dip and FOB plus CXR) detected majority of cancer in previous studies (Cornuz 1996).
  • Monreal et al (2004) studied 864 patients with uVTE. With routine investigations (which included an USS of the abdomen, CEA, CA125, and CEA) 56% of cancers were detected. However a further 23% of those developing cancer by one year had undetectable disease at the time they developed their uVTE.
  • The SOMIT study was the RCT looking at the role for extensive screening for cancer in uVTE. They took 201 patients with a new VTE and all underwent History and exam, CXR, urine and basic bloods. Those with nil found at this point were randomised to follow up or extensive investigations (CT and USS of abdo/pelvis, OGD, colonoscopy, sputum cytology, tumour markers, mammogram, cervical smear, prostatic USS and PSA, stool guaiac examination). Cancer was detected at a higher rate in the extensive investigation group (13 in 99 patients versus none of 102 in the follow-up arm) and the CT scans had the highest yielding investigation.

But does earlier detection of cancer affect survival?

  • In the SOMIT study survival at 2 years was equivocal between arms (death 2% in extensively investigated arm v 4% in follow up arm with non-significant p-value). This study has led to a general, though not universal, opinion that a good history, examination and basic investigations are appropriate, but that further investigation should be guided by patient symptoms/signs and not be applied without due thought.
  • A further study (Van Doormaal et al 2011) looked at the utility of extensive cancer screening for VTE patients, performing a prospective cohort study of 630 patients, receiving basic or more extensive investigations. Once again the study concluded that aggressive investigation was not supported by the data in terms of cancer deaths or overall survival.

Current (UK) Practice

  • In the UK NICE (2012) recommends ‘considering further investigation for cancer with an abdo-pelvic CT (+mammogram in women) in all patients over 40 who do not signs or symptoms of cancer based on initial investigations). The BCSH guidelines (2105) state that these investigations should be considered but should not be routine.
  • Although it can be argued that there are benefits to detecting cancer early which are not reflected in survivorship data, there are also drawbacks of extra investigation – anxiety for the (ultimately cancer-negative) patient, over investigation of ‘incidentalomas’, cost and radiation exposure. As with all screening programmes it is important to minimise harm from investigation.

Thanks for joining the case. Feedback is always welcome @teamhaem. Please join us again for the next case – our big 4-0.

References and Resources

Carrier, M., Khorana, A.A., Zwicker, J.I., Noble, S. & Lee, A.Y. (2013) Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. Journal of Thrombosis and Haemostasis, 11, 1760-1765.

Cornuz J, Pearson SD, Creager MA, et al. Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. Ann Intern Med. 1996; 125: 785–793

Monreal, M., Lensing, A.W., Prins, M.H., Bonet, M., Fernandez-Llamazares, J., Muchart, J., Prandoni, P. & Jimenez, J.A. (2004) Screening for occult cancer in patients with acute deep vein thrombosis or pulmonary embolism. Journal of Thrombosis and Haemostasis, 2, 876-881.

Piccioli, A., Lensing, A.W., Prins, M.H., Falanga, A., Scannapieco, G.L., Ieran, M., Cigolini, M., Ambrosio, G.B., Monreal, M., Girolami, A. & Prandoni, P. (2004) Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial. Journal of Thrombosis and Haemostasis, 2, 884-889.

Sorensen, H.T., Mellemkjaer, L., Olsen, J.H. & Baron, J.A. (2000) Prognosis of cancers associated with venous thromboembolism. New England Journal of Medicine, 343, 1846-1850.

Van Doormaal, F.F., Terpstra, W., Van Der Griend, R., Prins, M.H., Nijziel, M.R., Van De Ree, M.A., Buller, H.R., Dutilh, J.C., ten Cate-Hoek, A., Van Den Heiligenberg, S.M., Van Der Meer, J. & Otten, J.M. (2011b) Is extensive screening for cancer in idiopathic venous thromboembolism warranted? Journal of Thrombosis and Haemostasis, 9, 79-84

NICE GUIDANCE 2012 http://www.nice.org.uk/guidance/cg144/chapter/1-recommendations

BCSH GUIDELINE: Guideline on aspects of cancer-related venous thrombosis by Henry G Watson, David M Keeling, Mike Laffan, R Campbell Tait & Mike Makris on behalf of the British Committee for Standards in Haematology (2015). http://www.bcshguidelines.com/documents/SE_GL_00439.pdf

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