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Journal of Clinical and
Translational Research Hidden cancer after VTE

1. Introduction formulated following the PICO method: P (patients):
Patients with unprovoked VTE; I (intervention): Extensive
Venous thromboembolism (VTE), including deep vein tests; C (comparator): Tests at physician’s discretion; O
thrombosis (DVT) of the lower limb and pulmonary (outcomes/results): Occult cancer.
embolism (PE), can be the earliest sign of occult cancer.
1-4
Armand Trousseau first reported the relationship 2.1. Literature search
between thrombosis and cancer in 1865, describing
thrombophlebitis in a woman with a gastric neoplasm. Using PubMed (https://pubmed-ncbi-nlm-nih-gov.bvsspa.
Research from cohort studies and broad-scale registries idm.oclc.org), Web of Science (https://www.webofscience.
has reported a prevalence of occult cancer of 5 ‒ 10% com), Cochrane Library (https://www.cochranelibrary.
within 12 months of VTE diagnosis. Hence, clinicians com/), Scopus (https://www.scopus.com), EMBASE
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should maintain a high level of suspicion of cancer in (https://www.embase.com), the international clinical trials
patients with acute VTE. Lymphomas and solid tumors registration platform Clinical Trials (https://clinicaltrials.
of the ovary, pancreas, kidney, stomach, and brain are the gov/), the International Clinical Trials Registry Platform
most common neoplasms identified. The incidence of (https://www.who.int/clinical-trials-registry-platform),
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occult cancer detection varies according to the presence and the Cochrane Central Register of Controlled Trials
or absence of risk factors for VTE. A systematic review (https://www.cochranelibrary.com/central), we searched
reported a 12-month prevalence of occult cancer of 2.6% for literature on occult cancer detection in patients with
(95% confidence interval [CI]: 1.6 ‒ 3.6) and 10% (95% CI: a first VTE from January 2000 to December 2023. The
8.6 ‒ 11.3) in patients with provoked and unprovoked VTE, following retrieval strategy (MeSH word or text word)
respectively. The incidence of occult cancer detection also was employed: DVT, occult malignancy, occult cancer,
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varies depending on whether the VTE is a first episode PE, screening, VTE, and thrombosis. The search strategy
or a recurrent event. The incidence of cancer in patients applied in each database comprised a combination of these
with recurrent idiopathic DVT is significantly higher than terms in the heading. The search was limited to studies on
that in patients with a first idiopathic DVT (odds ratio humans without language restrictions.
[OR]: 4.3; 95% CI: 1.2 ‒ 15.3). Studies have also evaluated 2.2. Study selection
5
whether the site of VTE is a risk factor for occult cancer. In
a systematic review, the 12-month prevalence of cancer was To be eligible, studies must investigate the effectiveness
similar in patients with PE with or without concomitant of extensive screening for undiagnosed malignancies
DVT (OR: 5.2%; 95% CI: 3.2 ‒ 8.2) than in patients with in reducing cancer-related mortality in adult patients
only DVT (OR: 5.6%; 95% CI: 4.4 ‒ 7.2). 11 with a first episode of VTE. These studies can compare
comprehensive screening strategies with a limited
The highest incidence of cancer diagnoses is observed approach. Eligibility requires that the VTE diagnosis be
within the 1 months after the thrombotic event. A Danish objectively confirmed through ventilation-perfusion scans,
st
study reported that the risk was substantially elevated computed tomography (CT), pulmonary angiography for
for all cancers during the first 6 months of follow-up PE, and ultrasonography for diagnosing lower extremity
and declined rapidly after 1 year from VTE diagnosis. DVT. A minimum follow-up period of 12 months is
2
Similarly, in a study conducted by Nordström et al., the required. Exclusion criteria were as follows: (i) review
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frequency of malignancy in patients with unprovoked articles; (ii) duplicate publications; (iii) studies without
DVT was significantly higher during the first 6 months usable data; (iv) cross‐sectional studies; (v) small case
after thrombosis diagnosis.
series and case reports; and (vi) conference abstracts. Three
It may seem appealing for clinicians to screen patients reviewers (A.F.M., J.M., and C.L.A.A.) screened titles and
with unprovoked VTE for occult cancer to detect abstracts of all retrieved records and, subsequently, full‐text
underlying neoplasms at an early and more treatable stage. articles, independently and in duplicate. A fourth reviewer
However, the extent to which patients with VTE should be (A.M.C.M.) resolved discrepancies when necessary. To aid
screened for occult cancer is controversial. This systematic the screening process, the reviewers used a standardized
review will focus on the evidence regarding occult cancer screening.
detection in patients presenting with idiopathic VTE.
2.3. Data extraction
2. Methods Using a standardized form, data from the included studies
According to the recommendations of the Preferred were extracted by A.F.M., J.M., and C.L.A.A. and reviewed
Reporting Items for Systematic Review and Meta-Analyses by A.M.C.M. The following data were extracted: (i) study
(PRISMA) 2020 Guidelines, a research question was setting (country, year of publication, data collection
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Volume 11 Issue 4 (2025) 4 doi: 10.36922/jctr.24.00069